AzTrials
AzTrials

Rectal AdenocarcinomaPhase 2NCT02921256

Veliparib, Pembrolizumab, and Combination Chemotherapy in Treating Patient With Locally Advanced Rectal Cancer

A Phase 2 study testing Capecitabine, Fluorouracil and Intensity-Modulated Radiation Therapy in people with Rectal Adenocarcinoma and Stage II Rectal Cancer AJCC v7, run by National Cancer Institute (NCI) at 650 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This randomized phase II trial studies how well veliparib or pembrolizumab work with combination chemotherapy and radiation therapy in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Capecitabine, Fluorouracil and Intensity-Modulated Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
363 participants
Where
650 sitesin 2 countries
Study dates
11 Jan 2017to 20 Sep 2023
Phase
Phase 2

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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Diagnosis of adenocarcinoma of the rectum with the major portion of the tumor intact; Note: prior to randomization, the investigator must specify and document each of the following:
  • Distance of the lowest tumor margin from the anal verge; and
  • Intent for sphincter sparing or non-sphincter sparing surgical resection according to the primary surgeon; and
  • The majority of the untreated tumor must be < 12 cm from the anal verge or below the peritoneal reflection as determined by the treating surgeon
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  • The tumor must be clinically determined to be locally advanced stage II or stage III rectal cancer, and must also meet any ONE of the following criteria:
  • Distal location (as defined by measurement on magnetic resonance imaging [MRI], transrectal ultrasound [ERUS]/pelvic computed tomography [CT] [with IV contrast] scan or palpable on digital rectal examination [DRE]): cT3-4 =< 5 cm from the anal verge, any N
  • Bulky: any cT4 or evidence that the tumor is adjacent to (defined as within 3 mm of) the mesorectal fascia on MRI or ERUS/pelvic CT (with IV contrast) scan
  • High risk for metastatic disease with 4 or more regional lymph nodes (cN2); clinical nodal or "cN" status for eligibility includes the total number of nodes (N2 = 4 or more) in the mesorectal and superior rectal stations measuring >= 1.0 cm in any axis on cross sectional or endoscopic imaging; Note: nodes must measure 1.0 cm or greater to be considered positive for this eligibility requirement
  • Not a candidate for sphincter-sparing surgical resection prior to neoadjuvant therapy (as planned by the primary surgeon)
  • Note: clinical stage of the primary tumor and nodes may be determined locally by rectal endoscopic ultrasound or pelvic MRI (pelvic MRI is strongly preferred); CT scan with IV contrast is acceptable provided there is evidence of T4 and/or N2 disease
  • Patients must have the ability to swallow and retain oral medication
  • Absolute neutrophil count (ANC) must be >= 1200/mm^3 (within 28 days before randomization)
  • Platelet count must be >= 100,000/mm^3 (within 28 days before randomization)
  • Hemoglobin must be >= 10 g/dL (within 28 days before randomization)
  • Total bilirubin must be =< ULN (upper limit of normal) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin (within 28 days before randomization)
  • Alkaline phosphatase must be =< 3 x ULN for the lab (within 28 days before randomization)
  • Aspartate aminotransferase (AST) must be =< 3 x ULN for the lab (within 28 days before randomization);
  • Note: if alanine aminotransferase (ALT) is performed instead of AST (per institution's standard practice), the ALT value must be =< 3 x ULN; if both were performed, the AST must also be =< 3 x ULN; if AST and/or ALT is >= ULN but =< 3 x ULN, serologic testing for hepatitis B and C must be performed and results for viral infection must be negative
  • Serum creatinine =< ULN for the lab and measured or calculated creatinine clearance > 60 mL/min (within 28 days before randomization)
  • Serum potassium, magnesium, and calcium levels within 28 days before randomization must be within normal limits (WNL) for the lab
  • International normalized ratio of prothrombin time (INR) within 28 days before randomization must be =< ULN for the lab; 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
  • Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease must:
  • Have a cluster of differentiation (CD)4 count >= 200 cells/uL within 30 days before beginning study therapy
  • Be off all antiretroviral therapy (prophylaxis/treatment) more than 60 days before beginning study therapy, and
  • Have no evidence of opportunistic infections
  • Pregnancy test (urine or serum beta-human chorionic gonadotropin [HCG]) done within 72 hours before randomization must be negative (for women of childbearing potential only); if urine pregnancy results are positive or cannot be confirmed as negative, a serum pregnancy test will be required

Who cannot join

  • Rectal cancer histology other than adenocarcinoma (i.e., sarcoma, lymphoma, squamous cell carcinoma, mucosal melanoma, etc.)
  • Definitive clinical or radiologic evidence of metastatic disease; required imaging studies must have been performed within 28 days prior to randomization; Note: Distant clinical staging to exclude patients with overt metastatic disease is determined by:
  • Chest: CT scan (preferred); chest x-ray posterioranterior (PA) and lateral (acceptable); or positron emission tomography (PET) scan (acceptable)
  • Abdomen: CT scan with IV contrast (preferred); or MRI (acceptable)
  • Pelvis: MRI (preferred) or CT scan with IV contrast (acceptable)
  • (It is recommended that the same imaging tests that are performed before randomization be used at follow-up time points; Note: CT scans of the abdomen and pelvis must be performed with IV contrast)
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  • History of prior invasive rectal malignancy, regardless of disease-free interval
  • Cardiac disease that would preclude the use of any of the drugs included in the GI002 treatment regimen; this includes but is not limited to:
  • Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker
  • Ventricular tachycardia or supraventricular tachycardia that requires treatment with class Ia antiarrhythmic drugs (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide); use of other antiarrhythmic drugs is permitted
  • Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker
  • Complete left bundle branch block (LBBB)
  • History of long QT syndrome
  • Corrected QT (QTc) >= 450 ms
  • Sensory or motor neuropathy >= grade 2
  • History of, or any evidence of active, non-infectious pneumonitis
  • Active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic) or have a history of abdominal surgery or other medical condition that may, in the opinion of the treating physician, interfere with gastrointestinal motility or absorption
  • Active autoimmune disease that has required systemic treatment within the past 2 years (i.e., with use of modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • History of active TB (Bacillus tuberculosis)
  • Active or chronic infection requiring systemic therapy
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy; the use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)
  • Active seizure disorder uncontrolled by medication
  • Any antineoplastic therapy for this cancer before randomization
  • Synchronous colon cancer
  • Other invasive cancer within 5 years before randomization; exceptions are colonic polyps, non-melanoma skin cancer or carcinoma-in-situ of the cervix
  • Antineoplastic therapy (e.g. chemotherapy or targeted therapy) for other invasive cancer within 5 years before randomization; (for the purposes of this study, hormonal therapy is not considered chemotherapy)
  • Prior treatment with an investigational compound being tested in this study (e.g., poly ADP ribose polymerase [PARP] inhibitor, anti-PD-1, anti-PD-L1, or anti-PD-L2)
  • Receipt of live vaccination within 28 days before randomization; seasonal flu vaccines that do not contain live virus are permitted
  • Major surgery within 4 weeks before randomization
  • Any therapeutic pelvic radiation
  • Known homozygous DPD (dihydro pyrimidine dehydrogenase) deficiency
  • Any of the following because this study involves agents that have known or potential genotoxic or mutagenic, and teratogenic effects:
  • Pregnant women
  • Nursing women who are unwilling to discontinue nursing
  • Men or women of childbearing potential who are unwilling to employ adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and for 4 months after the last dose of study therapy
  • Co-morbid illnesses or other concurrent disease that, in the judgement of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up

Trial locations and contacts

650 sites in 2 countries.

305 sites in 2 countries

United States300 sites

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Queen's Cancer Center - Pearlridge

    ‘Aiea, Hawaii, 96701

  • The Cancer Center of Hawaii-Pali Momi

    ‘Aiea, Hawaii, 96701

  • Avera Cancer Institute-Aberdeen

    Aberdeen, South Dakota, 57401

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Hickman Cancer Center

    Adrian, Michigan, 49221

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • Atrium Health Stanly/LCI-Albemarle

    Albemarle, North Carolina, 28002

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • New Mexico Oncology Hematology Consultants

    Albuquerque, New Mexico, 87109

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Kaiser Permanente-Deer Valley Medical Center

    Antioch, California, 94531

  • Northwest Community Hospital

    Arlington Heights, Illinois, 60005

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • Northwest Wisconsin Cancer Center

    Ashland, Wisconsin, 54806

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • MultiCare Auburn Medical Center

    Auburn, Washington, 98001

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush - Copley Medical Center

    Aurora, Illinois, 60504

  • AIS Cancer Center at San Joaquin Community Hospital

    Bakersfield, California, 93301

  • Saint Louis Cancer and Breast Institute-Ballwin

    Ballwin, Missouri, 63011

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • LSU Health Baton Rouge-North Clinic

    Baton Rouge, Louisiana, 70805

  • Louisiana Hematology Oncology Associates LLC

    Baton Rouge, Louisiana, 70809

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Our Lady of the Lake Physicians Group - Medical Oncology

    Baton Rouge, Louisiana, 70809

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan, 48706

  • Northwell Health Imbert Cancer Center

    Bay Shore, New York, 11706

  • UHHS-Chagrin Highlands Medical Center

    Beachwood, Ohio, 44122

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • Overlake Medical Center

    Bellevue, Washington, 98004

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • 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

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Parkland Health Center-Bonne Terre

    Bonne Terre, Missouri, 63628

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Boulder Community Hospital

    Boulder, Colorado, 80301

  • Rocky Mountain Cancer Centers-Boulder

    Boulder, Colorado, 80304

  • Bozeman Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Harrison HealthPartners Hematology and Oncology-Bremerton

    Bremerton, Washington, 98310

  • Harrison Medical Center

    Bremerton, Washington, 98310

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • United Hospital Center

    Bridgeport, West Virginia, 26330

  • Crozer-Keystone Regional Cancer Center at Broomall

    Broomall, Pennsylvania, 19008

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Highline Medical Center-Main Campus

    Burien, Washington, 98166

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Cleveland Clinic Mercy Hospital

    Canton, Ohio, 44708

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Southeast Cancer Center

    Cape Girardeau, Missouri, 63703

  • Memorial Hospital of Carbondale

    Carbondale, Illinois, 62902

  • SIH Cancer Institute

    Carterville, Illinois, 62918

  • Eden Hospital Medical Center

    Castro Valley, California, 94546

  • Sandra L Maxwell Cancer Center

    Cedar City, Utah, 84720

  • 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

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Geauga Hospital

    Chardon, Ohio, 44024

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • West Virginia University Charleston Division

    Charleston, West Virginia, 25304

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Atrium Health Pineville/LCI-Pineville

    Charlotte, North Carolina, 28210

  • Atrium Health University City/LCI-University

    Charlotte, North Carolina, 28262

  • Memorial Hospital

    Chattanooga, Tennessee, 37404

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Enloe Medical Center

    Chico, California, 95926

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • McLaren Cancer Institute-Clarkston

    Clarkston, Michigan, 48346

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Medical Oncology and Hematology Associates-West Des Moines

    Clive, Iowa, 50325

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • Baptist Memorial Hospital and Cancer Center-Collierville

    Collierville, Tennessee, 38017

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Atrium Health Cabarrus/LCI-Concord

    Concord, North Carolina, 28025

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • City of Hope Corona

    Corona, California, 92879

  • Mary Bird Perkins Cancer Center - Covington

    Covington, Louisiana, 70433

  • Northshore Oncology Associates-Covington

    Covington, Louisiana, 70433

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Genesis Medical Center - East Campus

    Davenport, Iowa, 52803

  • Genesis Cancer Care Institute

    Davenport, Iowa, 52804

  • Iowa Cancer Specialists

    Davenport, Iowa, 52807

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Dayton Physician LLC-Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Beaumont Hospital - Dearborn

    Dearborn, Michigan, 48124

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • SCL Health Saint Joseph Hospital

    Denver, Colorado, 80218

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Mission Cancer and Blood - Laurel

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Ascension Saint John Hospital

    Detroit, Michigan, 48236

  • Essentia Health Saint Mary's - Detroit Lakes Clinic

    Detroit Lakes, Minnesota, 56501

  • Cancer Center of Kansas - Dodge City

    Dodge City, Kansas, 67801

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Kaiser Permanente Dublin

    Dublin, California, 94568

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Saint Luke's Hospital of Duluth

    Duluth, Minnesota, 55805

  • Northeast Radiation Oncology Center

    Dunmore, Pennsylvania, 18512

  • Pocono Medical Center

    East Stroudsburg, Pennsylvania, 18301

  • Marshfield Clinic Cancer Center at Sacred Heart

    Eau Claire, Wisconsin, 54701

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Cancer Center of Kansas - El Dorado

    El Dorado, Kansas, 67042

  • Mercy Cancer Center-Elyria

    Elyria, Ohio, 44035

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Englewood Hospital and Medical Center

    Englewood, New Jersey, 07631

  • Saint Vincent Hospital

    Erie, Pennsylvania, 16544

  • Deaconess Clinic Downtown

    Evansville, Indiana, 47713

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • Essentia Health Cancer Center-South University Clinic

    Fargo, North Dakota, 58103

  • 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

  • Beaumont Hospital - Farmington Hills

    Farmington Hills, Michigan, 48336

  • Virginia Mason Federal Way Medical Center

    Federal Way, Washington, 98002

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Orion Cancer Care

    Findlay, Ohio, 45840

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • Singh and Arora Hematology Oncology PC

    Flint, Michigan, 48532

  • Aurora Health Center-Fond du Lac

    Fond du Lac, Wisconsin, 54937

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Mercy Hospital Fort Smith

    Fort Smith, Arkansas, 72903

  • Parkview Hospital Randallia

    Fort Wayne, Indiana, 46805

  • Parkview Regional Medical Center

    Fort Wayne, Indiana, 46845

  • Essentia Health - Fosston

    Fosston, Minnesota, 56542

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Kaiser Permanente-Fremont

    Fremont, California, 94538

  • Fresno Cancer Center

    Fresno, California, 93720

  • Kaiser Permanente-Fresno

    Fresno, California, 93720

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida, 32610

  • Northeast Georgia Medical Center-Gainesville

    Gainesville, Georgia, 30501

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • University of Texas Medical Branch

    Galveston, Texas, 77555-0565

  • Central Care Cancer Center - Garden City

    Garden City, Kansas, 67846

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • The West Clinic - Wolf River

    Germantown, Tennessee, 38138

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Tacoma/Valley Radiation Oncology Centers-Gig Harbor

    Gig Harbor, Washington, 98332

  • MultiCare Gig Harbor Medical Park

    Gig Harbor, Washington, 98335

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Crozer Regional Cancer Center at Brinton Lake

    Glen Mills, Pennsylvania, 19342

  • Glens Falls Hospital

    Glens Falls, New York, 12801

  • Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • CHI Health Saint Francis

    Grand Island, Nebraska, 68803

  • Saint Mary's Hospital and Regional Medical Center

    Grand Junction, Colorado, 81501

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Central Care Cancer Center - Great Bend

    Great Bend, Kansas, 67530

  • Benefis Healthcare- Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • North Colorado Medical Center

    Greeley, Colorado, 80631

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Dayton Physicians LLC-Wayne

    Greenville, Ohio, 45331

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Baptist Cancer Center-Grenada

    Grenada, Mississippi, 38901

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • Sentara Cancer Institute at Sentara CarePlex Hospital

    Hampton, Virginia, 23666

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • OptumCare Cancer Care at Seven Hills

    Henderson, Nevada, 89052

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Island Urology

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Hawaii Cancer Care Inc-Liliha

    Honolulu, Hawaii, 96817

  • Kuakini Medical Center

    Honolulu, Hawaii, 96817

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • The Cancer Center of Hawaii-Liliha

    Honolulu, Hawaii, 96817

  • Kaiser Permanente Moanalua Medical Center

    Honolulu, Hawaii, 96819

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • CHI Saint Vincent Cancer Center Hot Springs

    Hot Springs, Arkansas, 71913

  • Mary Bird Perkins Cancer Center - Houma

    Houma, Louisiana, 70360

  • Oncology Center of The South Incorporated

    Houma, Louisiana, 70360

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Ben Taub General Hospital

    Houston, Texas, 77030

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Novant Health Presbyterian Medical Center Huntersville

    Huntersville, North Carolina, 28078

  • Franciscan Health Indianapolis

    Indianapolis, Indiana, 46237

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Allegiance Health

    Jackson, Michigan, 49201

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Essentia Health - Jamestown Clinic

    Jamestown, North Dakota, 58401

  • Capital Region Southwest Campus

    Jefferson City, Missouri, 65109

  • Jefferson Hospital

    Jefferson Hills, Pennsylvania, 15025

  • UW 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

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Borgess Medical Center

    Kalamazoo, Michigan, 49048

  • Kalispell Regional Medical Center

    Kalispell, Montana, 59901

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Research Medical Center

    Kansas City, Missouri, 64132

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • Tri-Cities Cancer Center

    Kennewick, Washington, 99336

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Greater Dayton Cancer Center

    Kettering, Ohio, 45409

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Seattle Cancer Care Alliance at EvergreenHealth

    Kirkland, Washington, 98034

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • Saint Anthony Hospital

    Lakewood, Colorado, 80228

  • City of Hope Antelope Valley

    Lancaster, California, 93534

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan, 48910

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • McLaren Cancer Institute-Lapeer Region

    Lapeer, Michigan, 48446

  • OptumCare Cancer Care at Charleston

    Las Vegas, Nevada, 89102

  • Radiation Oncology Centers of Nevada Central

    Las Vegas, Nevada, 89106

  • GenesisCare USA - Las Vegas

    Las Vegas, Nevada, 89109

  • OptumCare Cancer Care at MountainView

    Las Vegas, Nevada, 89128

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89148

  • OptumCare Cancer Care at Fort Apache

    Las Vegas, Nevada, 89148

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • Cancer Centers of Southwest Oklahoma Research

    Lawton, Oklahoma, 73505

  • UTMB Cancer Center at Victory Lakes

    League City, Texas, 77573

Other trials in United States

Puerto Rico5 sites

  • Cancer Center-Metro Medical Center Bayamon

    Bayamón, 00959-5060

  • Doctors Cancer Center

    Manati, 00674

  • San Juan Community Oncology Group

    San Juan, 00917

  • Centro Comprensivo de Cancer de UPR

    San Juan, 00927

  • San Juan City Hospital

    San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: A Phase II Clinical Trial Platform of Sensitization Utilizing Total Neoadjuvant Therapy (TNT) in Rectal Cancer

This randomized phase II trial studies how well veliparib or pembrolizumab work with combination chemotherapy and radiation therapy in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as modified (m)FOLFOX6 regimen, 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving veliparib or pembrolizumab with combination chemotherapy and radiation therapy may kill more tumor cells, make the tumor smaller, and reduce the amount of normal tissue that needs to be removed.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To demonstrate an absolute improvement in neoadjuvant rectal cancer (NAR) score for the experimental regimen as compared to concurrently randomized control patients.

SECONDARY OBJECTIVES:

  1. To compare overall survival (OS). II. To compare disease-free survival (DFS). III. To compare the rate of pathologic complete response (pCR) (nodes and tumor).

IV. To compare the rate of sphincter preservation.

TERTIARY OBJECTIVES:

  1. To compare the proportion of patients who have a tumor resection overall, conditional on beginning induction chemotherapy, and conditional on beginning chemoradiotherapy.

II. To compare time from initiation of chemoradiotherapy to surgery in the subset of patients with tumor resection.

EXPLORATORY OBJECTIVES:

  1. To estimate the rate of disease progression during chemotherapy (prior to chemoradiation).

II. To compare the rate of clinical complete response rate (cCR). III. To compare the rate of negative circumferential margin. IV. To compare the rate of completion of all cycles of neoadjuvant chemotherapy.

  1. To compare the rate of completion of full course of chemoradiation. VI. To compare the toxicity and safety between interventions. VII. To explore the correlative molecular predictors of response and distant failure.

VIII. To explore the relationship between radiographic findings and pathologic outcomes.

OUTLINE: Patients are sequentially randomized to treatment arms, initially ARM I or ARM II and then later either ARM I or ARM III.

ARM I: Patients receive mFOLFOX6 regimen consisting of oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo radiation therapy (RT) and receive capecitabine orally (PO) twice daily (BID) Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID and veliparib PO BID Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID Monday-Friday for 5 weeks. They also receive pembrolizumab IV over 30 minutes every 3 weeks beginning on day 1 of RT for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 6 months for up to 3 years.

Being tested
Capecitabine, Fluorouracil, Intensity-Modulated Radiation Therapy, Leucovorin, Oxaliplatin
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given PO

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Undergo intensity modulated radiation therapy

  • LeucovorinDrug

    Also called Folinic acid

    Given IV

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IV

  • PembrolizumabBiological

    Also called BCD-201, Keytruda, Lambrolizumab, MK-3475

    Given IV

  • VeliparibDrug

    Also called ABT-888, PARP-1 inhibitor ABT-888

    Given PO

Study groups in NCT02921256
Study groupRoleWhat they receive
Arm I (mFOLFOX6, RT, capecitabine)Active comparatorPatients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity. Participants assigned to Arm I concurrently with Arm II or with Arm III.
Receives: Drug: Capecitabine; Drug: Fluorouracil; Radiation: Intensity-Modulated Radiation Therapy; Drug: Leucovorin; Drug: Oxaliplatin
Arm II (mFOLFOX6, RT, capecitabine, veliparib)ExperimentalPatients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID and veliparib PO BID Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Capecitabine; Drug: Fluorouracil; Radiation: Intensity-Modulated Radiation Therapy; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Veliparib
Arm III (mFOLFOX6, RT, capecitabine, pembrolizumab)ExperimentalARM III: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo RT and receive capecitabine PO BID Monday-Friday for 5 weeks. They also receive pembrolizumab IV over 30 minutes every 3 weeks beginning on day 1 of RT for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Capecitabine; Drug: Fluorouracil; Radiation: Intensity-Modulated Radiation Therapy; Drug: Leucovorin; Drug: Oxaliplatin; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Neoadjuvant Rectal Cancer (NAR) Score

    A linear regression model that controls for the stratification factors (cT-stage and cN-stage) will be used. Mean NAR scores along with standard errors and confidence intervals will be reported by treatment. The NAR score ranges from zero to 100 with lower values corresponding to better prognosis.

    Measured: Baseline to up to 3 years

Secondary outcomes (4)

  1. Overall Survival

    Analyzed using the stratified log rank test with strata cT-stage and cN-stage. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Cox regression models will be used to estimate hazard ratios and associated confidence intervals.

    Measured: Time from randomization, assessed up to 3 years

  2. Disease Free Survival

    Analyzed using the stratified log rank test with strata cT-stage and cN-stage. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Cox regression models will be used to estimate hazard ratios and associated confidence intervals.

    Measured: Time from randomization, assessed up to 3 years

  3. Rate of Pathologic Complete Response (Nodes and Tumor) ypT0 and ypN0

    Pathologic Complete Response means no remaining cancer detectable in the pathology sample. Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.

    Measured: Up to 3 years

  4. Rate of Sphincter Preservation

    Sphincter preservation means that the surgical procedure used to remove the tumor did not disturb the sphincter muscle. Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2016 (estimated)
  2. Study start11 Jan 2017
  3. Primary completion21 Apr 2020
  4. Study completion20 Sep 2023

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
363 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02921256
Sponsor's protocol ID
NCI-2016-00222
Other IDs
NCI-2016-00222, NRG-GI002, s17-00197, NRG-GI002, NRG-GI002, U10CA180868
Status last verified
Nov 2025
First submitted
30 Sep 2016
Last updated
4 Dec 2025
Data monitoring committee
Yes

Publications

  • Hall WA, Li J, You YN, Gollub MJ, Grajo JR, Rosen M, dePrisco G, Yothers G, Dorth JA, Rahma OE, Russell MM, Gross HM, Jacobs SA, Faller BA, George S, Al Baghdadi T, Haddock MG, Valicenti R, Hong TS, George TJ. Prospective Correlation of Magnetic Resonance Tumor Regression Grade With Pathologic Outcomes in Total Neoadjuvant Therapy for Rectal Adenocarcinoma. J Clin Oncol. 2023 Oct 10;41(29):4643-4651. doi: 10.1200/JCO.22.02525. Epub 2023 Jul 21.

    PubMed 37478389

  • Rahma OE, Yothers G, Hong TS, Russell MM, You YN, Parker W, Jacobs SA, Colangelo LH, Lucas PC, Gollub MJ, Hall WA, Kachnic LA, Vijayvergia N, O'Rourke MA, Faller BA, Valicenti RK, Schefter TE, George S, Kainthla R, Stella PJ, Sigurdson E, Wolmark N, George TJ. Use of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Initial Results From the Pembrolizumab Arm of a Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Aug 1;7(8):1225-1230. doi: 10.1001/jamaoncol.2021.1683.

    PubMed 34196693

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