Metastatic Colorectal AdenocarcinomaPhase 3NCT02997228
Testing the Addition of Atezolizumab to Combination Chemotherapy or Atezolizumab Alone for Metastatic Colon or Rectal Cancer, the COMMIT Study
A Phase 3 study testing Atezolizumab, Bevacizumab and Biospecimen Collection in people with Metastatic Colorectal Adenocarcinoma and Stage IV Colorectal Cancer AJCC v7, run by National Cancer Institute (NCI) at 445 sites in United States.
Trial summary
This phase III trial studies how well combination chemotherapy, bevacizumab, and/or atezolizumab work in treating patients with deficient deoxyribonucleic acid (DNA) mismatch repair colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Adenocarcinoma, Stage IV Colorectal Cancer AJCC v7
- What is being tested?
- Atezolizumab, Bevacizumab and Biospecimen Collection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 445 sitesUnited States
- Study dates
- 19 Jan 2018to 1 Jun 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer except for one cycle of FOLFOX or capecitabine and oxaliplatin (CAPOX), either with or without bevacizumab prior to enrollment. Upon enrollment, the preceding single cycle of FOLFOX or FOLFOX + bevacizumab, if the patient received one, will not count towards patients' assessments per protocol. Cycle 1 day 1 (C1D1) of atezolizumab or C1D1 of mFOLFOX6/bevacizumab + atezolizumab will correspond to the first day the patient received therapy on trial
- Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; alternatively, MSI-H diagnosed by polymerase chain reaction (PCR)-based assessment of microsatellite alterations (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) are eligible
- Documentation by PET/CT scan, CT scan, or MRI that the patient has measurable metastatic disease per RECIST 1.1
Show all 20Show fewer
- No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass
- Absolute neutrophil count (ANC) must be >= 1500/mm^3 (obtained within 28 days prior randomization)
- Platelet count must be >= 100,000/mm^3 (obtained within 28 days prior randomization)
- Hemoglobin must be >= 8 g/dL (obtained within 28 days prior randomization)
- Total bilirubin must be =< 4 x ULN (upper limit of normal) (obtained within 28 days prior randomization); and
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 3 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be =< 5 x ULN (obtained within 28 days prior randomization)
- Calculated creatinine clearance >= 30 mL/min (obtained within 28 days prior randomization)
- A urine sample tested for proteinuria by either the dipstick method, urinalysis (UA), or a urine protein creatinine (UPC) ratio:
- The dipstick method must indicate 0-1+ protein; if dipstick reading is >= 2+, a 24-hour urine must be done and it must demonstrate < 1.0 g of protein per 24 hours or a UPC ratio < 1.0
- A urine protein creatinine (UPC) ratio must be < 1.0; if the UPC ratio is >= 1.0 a 24-hour urine must be done and it must demonstrate < 1.0 g of protein per 24 hours
- Urinalysis must indicate < 30 mg/dl. If urinalysis >= 30 mg/dl, a 24-hour urine must be done and it must demonstrate < 1.0 g of protein per 24 hours or a UPC ratio < 1.0
- International normalized ratio of prothrombin time (INR) and prothrombin time (PT) must be =< 1.5 x ULN for the lab within 28 days before randomization; patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history, regardless of PT/INR results
- Pregnancy test done within 28 days prior randomization must be negative (for women of childbearing potential only); pregnancy testing should be performed according to institutional standards; administration of atezolizumab or mFOLFOX6/bevacizumab/atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Women of child-bearing potential and men must agree to use adequate contraception methods that result in a failure rate of < 1% per year during the treatment period (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, and 6 months after the last dose of mFOLFOX6; a woman is considered to be of childbearing potential if she is not postmenopausal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus); examples of contraceptive methods with a failure rate of < 1% per year include: bilateral tubal ligation; male partner sterilization; intrauterine devices; the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception; men must refrain from donating sperm during this same period
Who cannot join
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, fluoropyrimidines, folic acid derivatives or oxaliplatin
- Uncontrolled high blood pressure defined as systolic blood pressure (BP) > 150 mmHg or diastolic BP > 100 mmHg with or without anti-hypertensive medication; patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria
- Documented New York Heart Association (NYHA) class III or IV congestive heart failure
- Serious or non-healing wound, skin ulcer, or bone fracture
- History of inherited bleeding diathesis, gastrointestinal (GI) perforation, significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis or symptomatic peripheral ischemia, transient ischemic attack [TIA], cerebrovascular accident [CVA] or arterial thrombotic event), abdominal fistula, intra-abdominal abscess, or active GI bleeding (with cause not addressed) within 6 months prior to randomization, or other medical condition in the opinion of the treating oncologist that makes the risk of cardiovascular or bleeding complications with bevacizumab use unacceptably high
- Other malignancies are excluded unless the patient has completed therapy for the malignancy >= 12 months prior to randomization and is considered disease-free; patients with the following cancers are eligible if diagnosed and treated within the past 12 months: in situ carcinomas or basal cell and squamous cell carcinoma of the skin
Show all 38Show fewer
- Known DPD (dihydro pyrimidine dehydrogenase) deficiency
- Symptomatic peripheral sensory neuropathy >= grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0)
- Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization
- History of grade 2 hemoptysis (defined as 2.5 mL of bright red blood per episode) within 1 month prior to screening
- Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents; patients who have received prior treatment with anti-CTLA-4 may be enrolled provided the following requirements are met:
- Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose to randomization
- No history of severe immune-related adverse effects (CTCAE grade 3 and 4) from anti-CTLA-4
- Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization; however,
- Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily treatment with corticosteroids with a dose of =< 10 mg/day methylprednisolone equivalent) may be enrolled
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease; however,
- Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HbsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible if polymerase chain reaction (PCR) for hepatits B virus (HBV) ribonucleic acid (RNA) is negative per local guidelines
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA per local guidelines
- History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis; however,
- Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
- Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
- Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
- Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
- Rash must cover less than 10% of body surface area (BSA)
- Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
- No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
- History of idiopathic pulmonary fibrosis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or active or recently active (within 90 days of randomization) pneumonitis (including drug induced) that required systemic immunosuppressive therapy (i.e. corticosteroids, etc.). History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Patients with known active tuberculosis (TB) are excluded
- Severe infections within 28 days prior to randomization, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Signs or symptoms of infection within 14 days prior to randomization
- Received oral or intravenous (IV) antibiotics within 14 days prior to randomization; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
- The administration of a live, attenuated vaccine within 28 days prior to randomization
- Pregnant women are excluded from this study because atezolizumab is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab; these potential risks may also apply to other agents used in this study; (Note: pregnancy testing should be performed within 28 days prior to randomization according to institutional standards for women of childbearing potential)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
Trial locations and contacts
445 sites in 1 country.
300 sites in 1 country
United States300 sites
Avera Cancer Institute-Aberdeen
Aberdeen, South Dakota, 57401
Cleveland Clinic Akron General
Akron, Ohio, 44307
Phoebe Putney Memorial Hospital
Albany, Georgia, 31701
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Presbyterian Kaseman Hospital
Albuquerque, New Mexico, 87110
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Saint Luke's Cancer Center - Allentown
Allentown, Pennsylvania, 18104
The Don and Sybil Harrington Cancer Center
Amarillo, Texas, 79106
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
Community Hospital of Anaconda
Anaconda, Montana, 59711
Kaiser Permanente-Anaheim
Anaheim, California, 92806
AnMed Health Cancer Center
Anderson, South Carolina, 29621
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
Aspirus Cancer Care-Antigo-Volm Cancer Center
Antigo, Wisconsin, 54409
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
Ascension Northeast Wisconsin-Saint Elizabeth Cancer Center-Appleton
Appleton, Wisconsin, 54915
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
University Cancer and Blood Center LLC
Athens, Georgia, 30607
Augusta Oncology Associates PC-D'Antignac
Augusta, Georgia, 30901
Augusta Oncology Associates PC-Wheeler
Augusta, Georgia, 30909
Augusta University Medical Center
Augusta, Georgia, 30912
Harold Alfond Center for Cancer Care
Augusta, Maine, 04330
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado, 80012
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
Kaiser Permanente-Baldwin Park
Baldwin Park, California, 91706
Mercy Oncology and Hematology - Clayton-Clarkson
Ballwin, Missouri, 63011
Kaiser Permanente-Woodlawn Medical Center
Baltimore, Maryland, 21244
Eastern Maine Medical Center
Bangor, Maine, 04401
CommonSpirit Saint Joseph Hospital - Bardstown
Bardstown, Kentucky, 40004
McLaren Cancer Institute-Bay City
Bay City, Michigan, 48706
Beaufort Memorial Hospital
Beaufort, South Carolina, 29902
Baptist Hospitals of Southeast Texas Cancer Center
Beaumont, Texas, 77701
MaineHealth Waldo Hospital
Belfast, Maine, 04915
Kaiser Permanente-Bellflower
Bellflower, California, 90706
Strecker Cancer Center-Belpre
Belpre, Ohio, 45714
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Saint Charles Health System
Bend, Oregon, 97701
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704
Saint Luke's University Hospital-Bethlehem Campus
Bethlehem, Pennsylvania, 18015
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
University of Iowa Healthcare Cancer Services Quad Cities
Bettendorf, Iowa, 52722
MaineHealth Maine Medical Center - Biddeford
Biddeford, Maine, 04005
Billings Clinic Cancer Center
Billings, Montana, 59101
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
McLaren Cancer Institute-Bloomfield
Bloomfield, Michigan, 48302
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
McFarland Clinic - Boone
Boone, Iowa, 50036
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Boulder Community Foothills Hospital
Boulder, Colorado, 80303
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado, 80304
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Bristol Regional Medical Center
Bristol, Tennessee, 37620
Ballad Health Cancer Care - Bristol
Bristol, Virginia, 24201
Ascension Southeast Wisconsin Hospital-Elmbrook Campus-Brookfield
Brookfield, Wisconsin, 53045
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
Roswell Park Cancer Institute
Buffalo, New York, 14263
Kaiser Permanente-Burke Medical Center
Burke, Virginia, 22015
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Illinois CancerCare-Canton
Canton, Illinois, 61520
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Mercy Hospital
Cedar Rapids, Iowa, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Dayton Physicians LLC-Miami Valley South
Centerville, Ohio, 45459
Miami Valley Hospital South
Centerville, Ohio, 45459
Centralia Oncology Clinic
Centralia, Illinois, 62801
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Vandalia Health/CAMC Institute for Academic Medicine
Charleston, West Virginia, 25304
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Cheyenne Regional Medical Center-West
Cheyenne, Wyoming, 82001
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
Adena Regional Medical Center
Chillicothe, Ohio, 45601
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, 97015
Hematology Oncology Consultants-Clarkston
Clarkston, Michigan, 48346
McLaren Cancer Institute-Clarkston
Clarkston, Michigan, 48346
Newland Medical Associates-Clarkston
Clarkston, Michigan, 48346
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Billings Clinic-Cody
Cody, Wyoming, 82414
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909
Memorial Hospital North
Colorado Springs, Colorado, 80920
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri, 65212
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Mount Carmel East Hospital
Columbus, Ohio, 43213
Columbus Oncology and Hematology Associates Inc
Columbus, Ohio, 43214
Riverside Methodist Hospital
Columbus, Ohio, 43214
Grant Medical Center
Columbus, Ohio, 43215
The Mark H Zangmeister Center
Columbus, Ohio, 43219
Mount Carmel Health Center West
Columbus, Ohio, 43222
Doctors Hospital
Columbus, Ohio, 43228
John Muir Medical Center-Concord
Concord, California, 94520
UT MD Anderson - The Woodlands
Conroe, Texas, 77384
Cookeville Regional Medical Center
Cookeville, Tennessee, 38501
Parkland Memorial Hospital
Dallas, Texas, 75235
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Danbury Hospital
Danbury, Connecticut, 06810
Carle at The Riverfront
Danville, Illinois, 61832
Miami Valley Hospital
Dayton, Ohio, 45409
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636
Delaware Health Center-Grady Cancer Center
Delaware, Ohio, 43015
Grady Memorial Hospital
Delaware, Ohio, 43015
Denver Health Medical Center
Denver, Colorado, 80204
National Jewish Health-Main Campus
Denver, Colorado, 80206
AdventHealth Porter
Denver, Colorado, 80210
Rocky Mountain Cancer Centers-Midtown
Denver, Colorado, 80218
Saint Joseph Hospital - Cancer Centers of Colorado
Denver, Colorado, 80218
Rocky Mountain Cancer Centers-Rose
Denver, Colorado, 80220
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Broadlawns Medical Center
Des Moines, Iowa, 50314
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
University of Maryland Shore Medical Center at Easton
Easton, Maryland, 21601
Saint Luke's Hospital-Anderson Campus
Easton, Pennsylvania, 18045
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
STCC at DHR Health Institute for Research and Development
Edinburg, Texas, 78539
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Arnot Ogden Medical Center/Falck Cancer Center
Elmira, New York, 14905
Mountain Blue Cancer Care Center - Swedish
Englewood, Colorado, 80113
Swedish Medical Center
Englewood, Colorado, 80113
Saint Vincent Hospital
Erie, Pennsylvania, 16544
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
Augusta Health Center for Cancer and Blood Disorders
Fishersville, Virginia, 22939
McLaren Cancer Institute-Flint
Flint, Michigan, 48532
Singh and Arora Hematology Oncology PC
Flint, Michigan, 48532
Kaiser Permanente-Fontana
Fontana, California, 92335
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
UI Healthcare Mission Cancer and Blood - Fort Dodge
Fort Dodge, Iowa, 50501
Broward Health Medical Center
Fort Lauderdale, Florida, 33316
Regional Cancer Center-Lee Memorial Health System
Fort Myers, Florida, 33905
Reiman Cancer Center-Ascension Wisconsin Health Center-Rawson
Franklin, Wisconsin, 53132
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Kaiser Permanente-Gaithersburg Medical Center
Gaithersburg, Maryland, 20879
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026
National Jewish Health-Western Hematology Oncology
Golden, Colorado, 80401
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, 27534
Altru Cancer Center
Grand Forks, North Dakota, 58201
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Great Falls Clinic
Great Falls, Montana, 59405
Banner North Colorado Medical Center
Greeley, Colorado, 80631
UCHealth Greeley Hospital
Greeley, Colorado, 80631
Bellin Memorial Hospital
Green Bay, Wisconsin, 54301
Saint Francis Hospital
Greenville, South Carolina, 29601
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Saint Francis Cancer Center
Greenville, South Carolina, 29607
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
Baptist Cancer Center-Grenada
Grenada, Mississippi, 38901
The Cancer Institute of New Jersey Hamilton
Hamilton, New Jersey, 08690
Kaiser Permanente South Bay
Harbor City, California, 90710
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania, 17109
Hartford Hospital
Hartford, Connecticut, 06102
HaysMed
Hays, Kansas, 67601
Saint Peter's Community Hospital
Helena, Montana, 59601
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, 28791
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035
Lyndon Baines Johnson General Hospital
Houston, Texas, 77026-1967
Houston Methodist Hospital
Houston, Texas, 77030
UT MD Anderson Cancer Center
Houston, Texas, 77030
UT MD Anderson - West Houston
Houston, Texas, 77079
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Community Cancer Center East
Indianapolis, Indiana, 46219
Community Cancer Center South
Indianapolis, Indiana, 46227
Franciscan Health Indianapolis
Indianapolis, Indiana, 46237
Community Cancer Center North
Indianapolis, Indiana, 46256
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Kaiser Permanente-Irvine
Irvine, California, 92618
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029
Allegiance Health
Jackson, Michigan, 49201
Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, 28546
Mercyhealth Hospital and Cancer Center - Janesville
Janesville, Wisconsin, 53548
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129
Jefferson Hospital
Jefferson Hills, Pennsylvania, 15025
Wellmont Medical Associates Oncology and Hematology-Johnson City
Johnson City, Tennessee, 37604
University of Wisconsin Carbone Cancer Center - Johnson Creek
Johnson Creek, Wisconsin, 53038
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, 72401
Freeman Health System
Joplin, Missouri, 64804
Mercy Hospital Joplin
Joplin, Missouri, 64804
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Logan Health Medical Center
Kalispell, Montana, 59901
University Health Truman Medical Center
Kansas City, Missouri, 64108
ECU Health Oncology Kenansville
Kenansville, North Carolina, 28349
Ochsner Medical Center Kenner
Kenner, Louisiana, 70065
Greater Dayton Cancer Center
Kettering, Ohio, 45409
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Kingman Regional Medical Center
Kingman, Arizona, 86401
Ballad Health Cancer Care - Kingsport
Kingsport, Tennessee, 37660
Wellmont Holston Valley Hospital and Medical Center
Kingsport, Tennessee, 37660
ECU Health Oncology Kinston
Kinston, North Carolina, 28501
Community Howard Regional Health
Kokomo, Indiana, 46904
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Franciscan Saint Elizabeth Health - Lafayette East
Lafayette, Indiana, 47905
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
Fairfield Medical Center
Lancaster, Ohio, 43130
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan, 48910
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
McLaren Cancer Institute-Lapeer Region
Lapeer, Michigan, 48446
Kaiser Permanente - Largo Medical Center
Largo, Maryland, 20774
Memorial Medical Center-Las Cruces
Las Cruces, New Mexico, 88011
OptumCare Cancer Care at Charleston
Las Vegas, Nevada, 89102
OptumCare Cancer Care at MountainView
Las Vegas, Nevada, 89128
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada, 89183
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505
UT MD Anderson - League City
League City, Texas, 77573
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Baptist Health Lexington
Lexington, Kentucky, 40503
CommonSpirit Saint Joseph Medical Center - East Lexington
Lexington, Kentucky, 40509
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Rocky Mountain Cancer Centers-Littleton
Littleton, Colorado, 80120
Hope Cancer Clinic
Livonia, Michigan, 48154
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Rocky Mountain Cancer Centers-Sky Ridge
Lone Tree, Colorado, 80124
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
Kaiser Permanente West Los Angeles
Los Angeles, California, 90034
Norton Hospital Pavilion and Medical Campus
Louisville, Kentucky, 40202
Norton Audubon Hospital and Medical Campus
Louisville, Kentucky, 40217
Norton Brownsboro Hospital and Medical Campus
Louisville, Kentucky, 40241
Medical Center of the Rockies
Loveland, Colorado, 80538
Banner North Colorado Medical Center - Loveland Campus
Loveland, Colorado, 80539
Lowell General Hospital
Lowell, Massachusetts, 01854
Kaiser Permanente Lutherville - Timonium Medical Center
Lutherville, Maryland, 21093
Centra Alan B Pearson Regional Cancer Center
Lynchburg, Virginia, 24501
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Dartmouth Cancer Center - Manchester/ DCC Manchester
Manchester, New Hampshire, 03104
OhioHealth Mansfield Hospital
Mansfield, Ohio, 44903
Cleveland Clinic Cancer Center Mansfield
Mansfield, Ohio, 44906
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109
Marietta Memorial Hospital
Marietta, Ohio, 45750
OhioHealth Marion General Hospital
Marion, Ohio, 43302
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Fremont - Rideout Cancer Center
Marysville, California, 95901
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124
Loyola University Medical Center
Maywood, Illinois, 60153
Kaiser Permanente Tysons Corner Medical Center
McLean, Virginia, 22102
Aspirus Medford Hospital
Medford, Wisconsin, 54451
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120
Midstate Medical Center
Meriden, Connecticut, 06451
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Woodland Cancer Care Center
Michigan City, Indiana, 46360
Beebe South Coastal Health Campus
Millville, Delaware, 19967
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Health Partners Inc
Minneapolis, Minnesota, 55454
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548
Community Medical Center
Missoula, Montana, 59804
Memorial Medical Center
Modesto, California, 95355
Forbes Hospital
Monroeville, Pennsylvania, 15146
Franciscan Health Mooresville
Mooresville, Indiana, 46158
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Morristown Medical Center
Morristown, New Jersey, 07960
McLaren Cancer Institute-Macomb
Mount Clemens, Michigan, 48043
McLaren Cancer Institute-Central Michigan
Mount Pleasant, Michigan, 48858
SSM Health Good Samaritan
Mount Vernon, Illinois, 62864
Knox Community Hospital
Mount Vernon, Ohio, 43050
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, 53149
About this study
Official title: Colorectal Cancer Metastatic dMMR/MSI-H Immuno-Therapy (COMMIT) Study: A Randomized Phase III Study of mFOLFOX6/Bevacizumab/Atezolizumab Combination Versus Single Agent Atezolizumab in the First-Line Treatment of Patients With Deficient DNA Mismatch Repair (dMMR)/Microsatellite Instability-High (MSI-H) Metastatic Colorectal Cancer
This phase III trial studies how well combination chemotherapy, bevacizumab, and/or atezolizumab work in treating patients with deficient deoxyribonucleic acid (DNA) mismatch repair colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as fluorouracil, oxaliplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of the tumor. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy, bevacizumab, and atezolizumab may work better in treating patients with colorectal cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the efficacy, based on progression-free survival (PFS), of fluorouracil, oxaliplatin, and leucovorin calcium (modified [m]FOLFOX6)/bevacizumab plus atezolizumab (combination) as compared to single agent atezolizumab.
SECONDARY OBJECTIVES:
- To compare the overall survival. II. To compare the objective response rates (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
III. To determine the safety profiles of single agent atezolizumab and the combination of mFOLFOX6/bevacizumab/atezolizumab in patients with mismatch-repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC).
IV. To determine the duration of response. V. To determine the duration of stable disease. VI. To determine the rate of progression-free survival (PFS) at 12 months. VII. To evaluate the disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) at 12 months.
TRANSLATIONAL OBJECTIVE:
- To bank tissue and blood samples for other future correlative studies from patients enrolled on the study.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I (CLOSED TO ACCRUAL 6/4/2020): Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 of cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1 and 2. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) with or without positron emission tomography (PET) or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
ARM III: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive bevacizumab IV over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on day 1. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
After completion of study treatment, patients are followed up every 8 weeks for 18 months, and then every 12 weeks for up to 5 years.
- Being tested
- Atezolizumab, Bevacizumab, Biospecimen Collection, Computed Tomography, Fluorouracil
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A
Given IV
BevacizumabBiological
Also called ABP 215, ABP-215, ABP215, Alymsys
Given IV
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood samples
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT or CT/PET
FluorouracilDrug
Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Given IV
LeucovorinDrug
Also called Folinic acid
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
OxaliplatinDrug
Also called 1-OHP, Ai Heng, Aiheng, Dacotin
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo CT/PET
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (bevacizumab, mFOLFOX6) | Active comparator | Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 of cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1 and 2. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. (CLOSED TO ACCRUAL) Receives: Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Leucovorin; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Arm II (atezolizumab) | Experimental | Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. Receives: Drug: Atezolizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Arm III (atezolizumab, bevacizumab, mFOLFOX6) | Experimental | Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive bevacizumab IV over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on day 1. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. Receives: Drug: Atezolizumab; Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Leucovorin; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
The analysis set is intent-to-treat (ITT). The experimental arms will be compared to the control arm by the log-rank test stratified by BRAF status (V600E mutation or not), metastatic disease: (liver-only, extra-hepatic), and prior adjuvant therapy for colon cancer (yes, no). Hazard ratios and associated confidence intervals from a stratified Cox regression model will also be reported along with estimates of the distributions of time to PFS event by the method of Kaplan and Meier. Sensitivity analyses accounting for 2 or more consecutively missed scheduled tumor imaging scans before progression/death will also be conducted.
Measured: From the time from randomization until first confirmed progression or death from any cause, assessed up to 5 years
Secondary outcomes (7)
Overall survival (OS)
Will be analyzed using the stratified log rank test and the ITT population. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Stratified Cox regression models will be used to estimate hazard ratios and associated confidence intervals.
Measured: The time from randomization to death from any cause, assessed up to 5 years
Objective response rate (ORR) (complete response [CR] or partial response [PR])
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be analyzed by a logistic regression models that control for the stratification factors (BRAF status, liver involvement, and adjuvant chemotherapy [chemo]) using the ITT population. Observed proportions along with confidence intervals will be presented by treatment.
Measured: Up to 5 years
Incidence of adverse events
Defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The safety profile will be described by tabulating the maximum observed grade of adverse event for each individual adverse event, for each system organ class, and overall using the Safety population.
Measured: Up to 30 days after last cycle
Rate of PFS
Measured: At 12 months
Disease control rate (CR + PR + stable disease [SD])
Assessed by RECIST 1.1. Will be analyzed by a logistic regression models that control for the stratification factors (BRAF status, liver involvement, and adjuvant chemo) using the ITT population. Observed proportions along with confidence intervals will be presented by treatment.
Measured: At 12 months
Duration of overall response (CR or PR)
Assessed by RECIST 1.1. Will be analyzed using the stratified log rank test and the ITT population. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Stratified Cox regression models will be used to estimate hazard ratios and associated confidence intervals.
Measured: From the time of first response to first confirmed progression by the study investigator or death from any cause, assessed up to 5 years
Duration of SD
Assessed per RECIST 1.1. Will be analyzed using the stratified log rank test and the ITT population. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Stratified Cox regression models will be used to estimate hazard ratios and associated confidence intervals.
Measured: From the time of first on-study assessment of SD to first progression by the study investigator or death from any cause, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study start19 Jan 2018
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- NRG Oncology
- Responsible party
- Sponsor
- Investigators
- Caio Max S Rocha Lima, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02997228
- Sponsor's protocol ID
- NCI-2016-01961
- Other IDs
- NCI-2016-01961, NRG-GI004/S1610, NRG-GI004, NRG-GI004, U10CA180868
- Status last verified
- Sep 2026
- First submitted
- 19 Dec 2016
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Rocha Lima CMSP, Yothers G, George TJ, Hochster HS, Sanoff HK, Cohen DJ, Guthrie KA, Jacobs SA, Saeed A, Kopetz S, Colangelo LH, Freeman TJ, Cole SW, Khalil M, Devanna S, Zuckerman DS, Hong TS, Henry NL, Ganz PA, Blanke CD, Wolmark N, Overman MJ. COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer. J Clin Oncol. 2026 Oct 10;44(29):2824-2834. doi: 10.1200/JCO-25-03052. Epub 2026 Jul 29.
PubMed 42525921
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Colorectal Cancer Metastatic dMMR/MSI-H Immuno-Therapy (COMMIT) Study: A Randomized Phase III Study of mFOLFOX6/Bevacizumab/Atezolizumab Combination Versus Single Agent Atezolizumab in the First-Line Treatment of Patients With Deficient DNA Mismatch Repair (dMMR)/Microsatellite Instability-High (MSI-H) Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02997228
- Acronym / sponsor ID
- NCI-2016-01961
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Collaborators
- NRG Oncology
- Study start
- 19 Jan 2018 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 20 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase III trial studies how well combination chemotherapy, bevacizumab, and/or atezolizumab work in treating patients with deficient deoxyribonucleic acid (DNA) mismatch repair colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as fluorouracil, oxaliplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of the tumor. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy, bevacizumab, and atezolizumab may work better in treating patients with colorectal cancer.
Detailed description
PRIMARY OBJECTIVE:
- To determine the efficacy, based on progression-free survival (PFS), of fluorouracil, oxaliplatin, and leucovorin calcium (modified [m]FOLFOX6)/bevacizumab plus atezolizumab (combination) as compared to single agent atezolizumab.
SECONDARY OBJECTIVES:
- To compare the overall survival. II. To compare the objective response rates (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
III. To determine the safety profiles of single agent atezolizumab and the combination of mFOLFOX6/bevacizumab/atezolizumab in patients with mismatch-repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC).
IV. To determine the duration of response. V. To determine the duration of stable disease. VI. To determine the rate of progression-free survival (PFS) at 12 months. VII. To evaluate the disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) at 12 months.
TRANSLATIONAL OBJECTIVE:
- To bank tissue and blood samples for other future correlative studies from patients enrolled on the study.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I (CLOSED TO ACCRUAL 6/4/2020): Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 of cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1 and 2. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) with or without positron emission tomography (PET) or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
ARM III: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive bevacizumab IV over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on day 1. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
After completion of study treatment, patients are followed up every 8 weeks for 18 months, and then every 12 weeks for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I (bevacizumab, mFOLFOX6) | Active comparator | Biological: Bevacizumab, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: Fluorouracil, Drug: Leucovorin, Procedure: Magnetic Resonance Imaging, Drug: Oxaliplatin, Procedure: Positron Emission Tomography, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 of cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1 and 2. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. (CLOSED TO ACCRUAL) |
| Arm II (atezolizumab) | Experimental | Drug: Atezolizumab, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Procedure: Positron Emission Tomography, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. |
| Arm III (atezolizumab, bevacizumab, mFOLFOX6) | Experimental | Drug: Atezolizumab, Biological: Bevacizumab, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: Fluorouracil, Drug: Leucovorin, Procedure: Magnetic Resonance Imaging, Drug: Oxaliplatin, Procedure: Positron Emission Tomography, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive bevacizumab IV over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on day 1. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer except for one cycle of FOLFOX or capecitabine and oxaliplatin (CAPOX), either with or without bevacizumab prior to enrollment. Upon enrollment, the preceding single cycle of FOLFOX or FOLFOX + bevacizumab, if the patient received one, will not count towards patients' assessments per protocol. Cycle 1 day 1 (C1D1) of atezolizumab or C1D1 of mFOLFOX6/bevacizumab + atezolizumab will correspond to the first day the patient received therapy on trial
- Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; alternatively, MSI-H diagnosed by polymerase chain reaction (PCR)-based assessment of microsatellite alterations (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) are eligible
Key exclusion criteria (38 listed)
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, fluoropyrimidines, folic acid derivatives or oxaliplatin
- Uncontrolled high blood pressure defined as systolic blood pressure (BP) > 150 mmHg or diastolic BP > 100 mmHg with or without anti-hypertensive medication; patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria
- Documented New York Heart Association (NYHA) class III or IV congestive heart failure
- Serious or non-healing wound, skin ulcer, or bone fracture
- History of inherited bleeding diathesis, gastrointestinal (GI) perforation, significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis or symptomatic peripheral ischemia, transient ischemic attack [TIA], cerebrovascular accident [CVA] or arterial thrombotic event), abdominal fistula, intra-abdominal abscess, or active GI bleeding (with cause not addressed) within 6 months prior to randomization, or other medical condition in the opinion of the treating oncologist that makes the risk of cardiovascular or bleeding complications with bevacizumab use unacceptably high
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtezolizumabAlso: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280AGiven IV | Drug | Arm II (atezolizumab), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| BevacizumabAlso: ABP 215, ABP-215, ABP215, AlymsysGiven IV | Biological | Arm I (bevacizumab, mFOLFOX6), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo collection of blood samples | Procedure or surgery | Arm I (bevacizumab, mFOLFOX6), Arm II (atezolizumab), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT or CT/PET | Procedure or surgery | Arm I (bevacizumab, mFOLFOX6), Arm II (atezolizumab), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| FluorouracilAlso: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedioneGiven IV | Drug | Arm I (bevacizumab, mFOLFOX6), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| LeucovorinAlso: Folinic acidGiven IV | Drug | Arm I (bevacizumab, mFOLFOX6), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Arm I (bevacizumab, mFOLFOX6), Arm II (atezolizumab), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| OxaliplatinAlso: 1-OHP, Ai Heng, Aiheng, DacotinGiven IV | Drug | Arm I (bevacizumab, mFOLFOX6), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo CT/PET | Procedure or surgery | Arm I (bevacizumab, mFOLFOX6), Arm II (atezolizumab), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Arm I (bevacizumab, mFOLFOX6), Arm II (atezolizumab), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
| Questionnaire AdministrationAncillary studies | Other | Arm I (bevacizumab, mFOLFOX6), Arm II (atezolizumab), Arm III (atezolizumab, bevacizumab, mFOLFOX6) |
Primary outcome
Progression free survival (PFS)
Time frame: From the time from randomization until first confirmed progression or death from any cause, assessed up to 5 years
The analysis set is intent-to-treat (ITT). The experimental arms will be compared to the control arm by the log-rank test stratified by BRAF status (V600E mutation or not), metastatic disease: (liver-only, extra-hepatic), and prior adjuvant therapy for colon cancer (yes, no). Hazard ratios and associated confidence intervals from a stratified Cox regression model will also be reported along with estimates of the distributions of time to PFS event by the method of Kaplan and Meier. Sensitivity analyses accounting for 2 or more consecutively missed scheduled tumor imaging scans before progression/death will also be conducted.
7 secondary outcomes
Overall survival (OS)
Time frame: The time from randomization to death from any cause, assessed up to 5 years
Objective response rate (ORR) (complete response [CR] or partial response [PR])
Time frame: Up to 5 years
Incidence of adverse events
Time frame: Up to 30 days after last cycle
Rate of PFS
Time frame: At 12 months
Disease control rate (CR + PR + stable disease [SD])
Time frame: At 12 months
Duration of overall response (CR or PR)
Time frame: From the time of first response to first confirmed progression by the study investigator or death from any cause, assessed up to 5 years
Duration of SD
Time frame: From the time of first on-study assessment of SD to first progression by the study investigator or death from any cause, assessed up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Derived from this study: PubMed 42525921Rocha Lima CMSP, Yothers G, George TJ, Hochster HS, Sanoff HK, Cohen DJ, Guthrie KA, Jacobs SA, Saeed A, Kopetz S, Colangelo LH, Freeman TJ, Cole SW, Khalil M, Devanna S, Zuckerman DS, Hong TS, Henry NL, Ganz PA, Blanke CD, Wolmark N, Overman MJ. COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer. J Clin Oncol. 2026 Oct 10;44(29):2824-2834. doi: 10.1200/JCO-25-03052. Epub 2026 Jul 29.
Related trials for Metastatic Colorectal Adenocarcinoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
Active, not recruitingPhase 1
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
Breast Cancer, Ovarian Cancer
RecruitingPhase 1/2
Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08032562 in People With Advanced or Metastatic Solid Tumors
Advanced Breast Cancer, Metastatic Breast Cancer (HR+/ HER2-)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Caio Max S Rocha Lima principal investigator
NRG Oncology
445 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atezolizumab, Bevacizumab and Biospecimen Collection in people with Metastatic Colorectal Adenocarcinoma and Stage IV Colorectal Cancer AJCC v7, run by National Cancer Institute (NCI) at 445 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 445 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) (time frame: From the time from randomization until first confirmed progression or death from any cause, assessed up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02997228, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.