AzTrials
AzTrials

Clear Cell Renal Cell CarcinomaPhase 3NCT03793166

Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study

A Phase 3 study testing Biospecimen Collection, Bone Scan and Cabozantinib in people with Clear Cell Renal Cell Carcinoma and Metastatic Malignant Neoplasm in the Bone, run by National Cancer Institute (NCI) at 859 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase III trial compares the usual treatment (treatment with ipilimumab and nivolumab followed by nivolumab alone) to treatment with ipilimumab and nivolumab, followed by nivolumab with cabozantinib in patients with untreated renal cell carcinoma that has spread to other parts of the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Scan and Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,175 participants
Where
859 sitesin 2 countries
Study dates
7 Jun 2019to 1 Mar 2028
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

  • STEP I REGISTRATION CRITERIA
  • Histologically documented renal cell carcinoma with clear cell component, including patients who have sarcomatoid or rhabdoid features
  • Any metastatic disease, including visceral, lymph node, other soft tissue and bone, measurable per RECIST 1.1
  • Measurable disease as defined in the protocol
  • Must be intermediate or poor risk patient per International Metastatic Renal Cell Carcinoma Database (IMDC) criteria (1 or more of the following): Karnofsky performance status [KPS] < 80, < 1 year from diagnosis [including initial nephrectomy] to systemic treatment for metastatic disease, hemoglobin less than lower limit of normal [LLN], corrected calcium concentration greater than upper limit of normal [ULN], absolute neutrophil count greater than ULN, platelet count > ULN)
  • Central nervous system (CNS) disease permitted, if stable and not otherwise causing symptoms or needing active treatment
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  • Karnofsky performance status >= 70%
  • No prior treatment with PD-1, PD-L1, or CTLA-4 targeting agents (including but not limited to nivolumab, pembrolizumab, pidilizumab, durvalumab, atezolizumab, tremelimumab, and ipilimumab), or any other drug or antibody specifically targeting T-cell co-stimulation or checkpoint pathways. The only exception is for prior treatment with nivolumab or other PD-1/PD-L1/CTLA-4 targeting therapy on pre- or post-operative trials, as long as > 1 year since completion of systemic therapy
  • No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 [>28 days]. Prior adjuvant sunitinib >180 days since completion and prior immunotherapy as above are allowed).
  • No systemic cancer therapy less than 28 days prior to registration; no radiation therapy less than 14 days prior to registration. There must be a complete recovery and no ongoing complications from radiotherapy
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =< 14 days prior to registration is required
  • Age >= 18 years
  • None of the following:
  • Active autoimmune disease requiring ongoing therapy
  • Ongoing acute toxicity > grade 2 from previous treatment
  • History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
  • Active hepatitis B/C, or active tuberculosis (purified protein derivative [PPD] response without active tuberculosis [TB] is allowed)
  • HIV-infected patients with detectable viral load within 6 months prior to registration. Patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible
  • Concurrent use of immunosuppressive medication including prednisone above 10 mg daily
  • Uncontrolled adrenal insufficiency
  • Uncontrolled hypertension (systolic blood pressure [BP] > 150mmHg or diastolic BP > 90mmHg)
  • Major surgery less than 28 days prior to registration
  • Any serious non-healing wound, ulcer, or bone fracture within 28 days prior to registration
  • Any arterial thrombotic events within 180 days prior to registration
  • Clinically significant hematuria, hematemesis, or hemoptysis within 12 weeks prior to registration
  • Cavitating pulmonary lesions or known endotracheal or endobronchial disease manifestations
  • Lesions encasing or invading any major blood vessels (this does not include tumor thrombus extending into/through renal vein/inferior vena cava [IVC]). Patients with tumor thrombus extending into/through renal vein are considered eligible
  • Moderate of severe hepatic impairment (child-Pugh B or C)
  • Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) in the 180 days prior to registration. (Any asymptomatic, treated pulmonary embolism or asymptomatic, treated deep venous thrombosis > 30 days prior to registration allowed)
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms
  • Unstable cardiac arrhythmia within 6 months prior to registration
  • Any gastrointestinal (GI) bleeding =< 180 days, hemoptysis, or other signs of pulmonary hemorrhage =< 90 days prior to registration
  • History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
  • Active peptic ulcer disease, inflammatory bowel disease, or malabsorption syndrome within 28 days prior to registration
  • Untreated hypothyroidism (treated hypothyroidism on thyroid replacement therapy is allowed. Abnormal thyroid-stimulating hormone [TSH] is acceptable with normal T3/free T4 if treated on thyroid replacement therapy)
  • Evidence of pancreatitis, history of organ transplant, or history of congenital QT syndrome
  • Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g., clopidogrel) within 5 days of registration Allowed anticoagulants include: prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, apixaban. Allowed also in patients with known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
  • Significant cardiac ischemia events (ST elevation myocardial infarction [STEMI] or non-ST-elevation myocardial infarction [NSTEMI]) within 6 months or active New York (NY) Heart Association class 3-4 heart failure symptoms
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 8 g/dL
  • Calculated (Calc.) creatinine clearance >= 30 mL/min
  • Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with known or likely Gilbert's syndrome, for whom total bilirubin up to 3 mg/dL is allowed with direct bilirubin =< 20% total bilirubin)
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 2.5 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present
  • STEP 2 REGISTRATION ELIGIBILITY CRITERIA
  • Successful completion of at least 1 cycle of ipilimumab/nivolumab
  • Resolution of any treatment-related adverse events to grade 1 or less per dose modification section (this criteria does not include any adverse events [AEs] not attributable to treatment which are present due to disease), with prednisone-equivalent dosing at 10 mg daily or less. Exceptions for this criteria include patients receiving replacement hormone treatments (such as levothyroxine for treatment-related hypothyroidism or glucocorticoid replacement for adrenal insufficiency). Please contact study chair if further discussion is needed
  • No more than 80 days from last dose of ipilimumab/nivolumab

Who cannot join

None listed.

Trial locations and contacts

859 sites in 2 countries.

301 sites in 2 countries

United States300 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • 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

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • Hickman Cancer Center

    Adrian, Michigan, 49221

  • Riverwood Healthcare Center

    Aitkin, Minnesota, 56431

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • University Cancer Specialists - Alcoa

    Alcoa, Tennessee, 37701

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • OSF Saint Anthony's Health Center

    Alton, Illinois, 62002

  • American Fork Hospital / Huntsman Intermountain Cancer Center

    American Fork, Utah, 84003

  • 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

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Anchorage Radiation Therapy Center

    Anchorage, Alaska, 99504

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic

    Ankeny, Iowa, 50023

  • 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

  • Mission Hope Medical Oncology - Arroyo Grande

    Arroyo Grande, California, 93420

  • PCR Oncology

    Arroyo Grande, California, 93420

  • AdventHealth Infusion Center Asheville

    Asheville, North Carolina, 28803

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • Northwest Wisconsin Cancer Center

    Ashland, Wisconsin, 54806

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Hematology Oncology Associates of Central New York-Auburn

    Auburn, New York, 13021

  • MultiCare Auburn Medical Center

    Auburn, Washington, 98001

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Dell Seton Medical Center at The University of Texas

    Austin, Texas, 78701

  • Saint Alphonsus Cancer Care Center-Baker City

    Baker City, Oregon, 97814

  • Kaiser Permanente-Baldwin Park

    Baldwin Park, California, 91706

  • Mercy Oncology and Hematology - Clayton-Clarkson

    Ballwin, Missouri, 63011

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • CommonSpirit Saint Joseph Hospital - Bardstown

    Bardstown, Kentucky, 40004

  • LSU Health Baton Rouge-North Clinic

    Baton Rouge, Louisiana, 70805

  • Our Lady of the Lake Physician Group

    Baton Rouge, Louisiana, 70808

  • Our Lady of The Lake

    Baton Rouge, Louisiana, 70808

  • Hematology/Oncology Clinic PLLC

    Baton Rouge, Louisiana, 70809

  • Louisiana Hematology Oncology Associates LLC

    Baton Rouge, Louisiana, 70809

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Ochsner High Grove

    Baton Rouge, Louisiana, 70836

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • MaineHealth Waldo Hospital

    Belfast, Maine, 04915

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Overlake Medical Center

    Bellevue, Washington, 98004

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • MaineHealth Maine Medical Center - Biddeford

    Biddeford, Maine, 04005

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Saint Vincent Frontier Cancer Center

    Billings, Montana, 59102

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Saint Elizabeth Boardman Hospital

    Boardman, Ohio, 44512

  • 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

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Parkland Health Center-Bonne Terre

    Bonne Terre, Missouri, 63628

  • 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

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Ocean University Medical Center

    Brick, New Jersey, 08724

  • United Hospital Center

    Bridgeport, West Virginia, 26330

  • 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

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Saint Anne Hospital

    Burien, Washington, 98166

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Minnesota Oncology - Burnsville

    Burnsville, Minnesota, 55337

  • Loyola Center for Health at Burr Ridge

    Burr Ridge, Illinois, 60527

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Cambridge Medical Center

    Cambridge, Minnesota, 55008

  • Hematology Oncology Associates of CNY at Camillus

    Camillus, New York, 13031

  • 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

  • Mercy Cancer Center - Cape Girardeau

    Cape Girardeau, Missouri, 63703

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • AtlantiCare Health Park-Cape May Court House

    Cape May Court House, New Jersey, 08210

  • Memorial Hospital of Carbondale

    Carbondale, Illinois, 62902

  • Caro Cancer Center

    Caro, Michigan, 48723

  • Saint Anthony Regional Hospital

    Carroll, Iowa, 51401

  • Carson Tahoe Regional Medical Center

    Carson City, Nevada, 89703

  • SIH Cancer Institute

    Carterville, Illinois, 62918

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Sandra L Maxwell Cancer Center

    Cedar City, Utah, 84720

  • Rocky Mountain Cancer Centers - Centennial

    Centennial, Colorado, 80112

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Vandalia Health/CAMC Institute for Academic Medicine

    Charleston, West Virginia, 25304

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Saint Luke's Hospital

    Chesterfield, Missouri, 63017

  • Cheyenne Regional Medical Center-West

    Cheyenne, Wyoming, 82001

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • 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

  • TriHealth Cancer Institute-Westside

    Cincinnati, Ohio, 45247

  • TriHealth Cancer Institute-Anderson

    Cincinnati, Ohio, 45255

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

  • Wake Forest University at Clemmons

    Clemmons, North Carolina, 27012

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • 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

  • Community Cancer Institute

    Clovis, California, 93611

  • University Oncology Associates

    Clovis, California, 93611

  • AdventHealth Infusion Center Haywood

    Clyde, North Carolina, 28721

  • Billings Clinic-Cody

    Cody, Wyoming, 82414

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Main Line Health Center-Collegeville

    Collegeville, Pennsylvania, 19426

  • 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

  • Memorial Hospital North

    Colorado Springs, Colorado, 80920

  • MU Health - University Hospital/Ellis Fischel Cancer Center

    Columbia, Missouri, 65212

  • Baptist Memorial Hospital and Cancer Center-Golden Triangle

    Columbus, Mississippi, 39705

  • 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

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Cookeville Regional Medical Center

    Cookeville, Tennessee, 38501

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Mary Imogene Bassett Hospital

    Cooperstown, New York, 13326

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Commonwealth Cancer Center-Corbin

    Corbin, Kentucky, 40701

  • Alegent Health Mercy Hospital

    Council Bluffs, Iowa, 51503

  • Northshore Oncology Associates-Covington

    Covington, Louisiana, 70433

  • Ochsner Hematology Oncology North Shore - Covington (West Region)

    Covington, Louisiana, 70433

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern Simmons Cancer Center - RedBird

    Dallas, Texas, 75237

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Premier Blood and Cancer Center

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Cancer Center of Colorado at Sloan's Lake

    Denver, Colorado, 80204

  • Kaiser Permanente-Franklin

    Denver, Colorado, 80205

  • National Jewish Health-Main Campus

    Denver, Colorado, 80206

  • UCHealth - Cherry Creek

    Denver, Colorado, 80206

  • The Women's Imaging Center

    Denver, Colorado, 80209

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • 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

  • Rose Medical Center

    Denver, Colorado, 80220

  • Western Surgical Care

    Denver, Colorado, 80220

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • 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

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Essentia Health Saint Mary's - Detroit Lakes Clinic

    Detroit Lakes, Minnesota, 56501

  • Illinois CancerCare-Dixon

    Dixon, Illinois, 61021

  • Columbus Oncology and Hematology Associates

    Dublin, Ohio, 43016

  • Dublin Methodist Hospital

    Dublin, Ohio, 43016

  • Northside Hospital - Duluth

    Duluth, Georgia, 30096

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • CommonSpirit Cancer Center Mercy

    Durango, Colorado, 81301

  • Mercy Medical Center

    Durango, Colorado, 81301

  • Durham VA Medical Center

    Durham, North Carolina, 27705

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Prisma Health Cancer Institute - Easley

    Easley, South Carolina, 29640

  • Henry Ford River District Hospital

    East China Township, Michigan, 48054

  • Pocono Medical Center

    East Stroudsburg, Pennsylvania, 18301

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • HSHS Sacred Heart Hospital

    Eau Claire, Wisconsin, 54701

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • AtlantiCare Surgery Center

    Egg Harbor, New Jersey, 08234

  • Elmhurst Memorial Hospital

    Elmhurst, Illinois, 60126

  • Walter Knox Memorial Hospital

    Emmett, Idaho, 83617

  • Mountain Blue Cancer Care Center - Swedish

    Englewood, Colorado, 80113

  • Rocky Mountain Cancer Centers - Swedish

    Englewood, Colorado, 80113

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • The Melanoma and Skin Cancer Institute

    Englewood, Colorado, 80113

  • Saint Elizabeth Hospital

    Enumclaw, Washington, 98022

  • OSF Saint Francis Hospital and Medical Group

    Escanaba, Michigan, 49829

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Main Line Health Center-Exton

    Exton, Pennsylvania, 19341

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Essentia Health Cancer Center-South University Clinic

    Fargo, North Dakota, 58103

  • Sanford South University Medical Center

    Fargo, North Dakota, 58103

  • Southpointe-Sanford Medical Center Fargo

    Fargo, North Dakota, 58103

  • Sanford Medical Center Fargo

    Fargo, North Dakota, 58104

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Parkland Health Center - Farmington

    Farmington, Missouri, 63640

  • Highlands Oncology Group - Fayetteville

    Fayetteville, Arkansas, 72703

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • 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

  • Augusta Health Center for Cancer and Blood Disorders

    Fishersville, Virginia, 22939

  • Cancer Hematology Centers - Flint

    Flint, Michigan, 48503

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • 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

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • Mercy Hospital Fort Smith

    Fort Smith, Arkansas, 72903

  • UT Southwestern/Simmons Cancer Center-Fort Worth

    Fort Worth, Texas, 76104

  • Essentia Health - Fosston

    Fosston, Minnesota, 56542

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • Central Ohio Breast and Endocrine Surgery

    Gahanna, Ohio, 43230

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

Other trials in United States

Puerto Rico1 site

  • Pan American Center for Oncology Trials LLC

    San Juan, 00902

Other trials in Puerto Rico

About this study

Official title: PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib With Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]

This phase III trial compares the usual treatment (treatment with ipilimumab and nivolumab followed by nivolumab alone) to treatment with ipilimumab and nivolumab, followed by nivolumab with cabozantinib in patients with untreated renal cell carcinoma that has spread to other parts of the body. The addition of cabozantinib to the usual treatment may make it work better. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known how well the combination of cabozantinib and nivolumab after initial treatment with ipilimumab and nivolumab works in treating patients with renal cell cancer that has spread to other parts of the body.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare the overall survival (OS) in patients with metastatic renal cell cancer (RCC) treated with ipilimumab-nivolumab followed by either nivolumab versus cabozantinib-nivolumab.

SECONDARY OBJECTIVES:

  1. To determine progression free survival (PFS) of patients treated with nivolumab versus nivolumab-cabozantinib.

II. To evaluate the 12-month complete response rate in patients treated with ipilimumab-nivolumab followed by cabozantinib-nivolumab versus ipilimumab-nivolumab followed by nivolumab (patients who have complete response [CR] and relapse before 12 months will not be counted as a CR at 12-months).

III. To evaluate the rates of discontinuing therapy at 1 year. IV. To compare objective response rates (ORR, assessed by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 and Immune Response Evaluation Criteria in Solid Tumors [iRECIST] criteria) for patients treated with ipilimumab-nivolumab followed by cabozantinib-nivolumab versus ipilimumab-nivolumab followed by nivolumab.

  1. To document the adverse event profile of ipilimumab-nivolumab followed by cabozantinib-nivolumab.

BIOMARKER OBJECTIVES:

  1. To evaluate biomarkers associated with exceptional responses in both arms (exceptional responses defined as CRs with treatment discontinuation at 12 months or 24 months).

II. To evaluate whether baseline IL-6 is predictive of outcome in patients treated with cabozantinib-containing regimen.

QUALITY OF LIFE (QOL) OBJECTIVES:

  1. To compare health-related quality of life at 18 months post-registration as assessed by the Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index 19 (FKSI-19) between patients randomized to nivolumab (nivo) versus (vs) cabozantinib (cabo)/nivo.

II. To compare health-related quality of life as assessed by the FKSI-19 between patients randomized to nivo vs cabo/nivo at other time points.

III. To compare patient-reported fatigue using Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue between patients randomized to nivo vs cabo/nivo.

IV. To compare quality-adjusted survival (overall survival x utility score assessed by EuroQol five-dimensional questionnaire [EQ5D-5L]) between patients randomized to nivo vs cabo/nivo.

OUTLINE:

INDUCTION: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

TREATMENT:

Patients with unconfirmed but clinical progression of disease (iuPD) with clinical instability receive cabozantinib orally (PO) daily on days 1-28. Treatment repeats every 28 days until further disease progression or unacceptable toxicity.

Patients with unconfirmed CR (iCR) receive nivolumab IV between 30-60 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with non-CR/non-PD or iuPD with clinical stability are randomized to 1 of 2 arms.

ARM A: Patients receive nivolumab IV between 30-60 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive nivolumab IV between 30-60 minutes on day 1 and cabozantinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood and urine sample collection, and may also undergo a bone scan as clinically indicated throughout the study.

Being tested
Biospecimen Collection, Bone Scan, Cabozantinib, Computed Tomography, Ipilimumab
Medical subject headings
Carcinoma, Renal Cell, Lymphatic Metastasis

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood and urine sample collection

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • CabozantinibDrug

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016

    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

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT03793166
Study groupRoleWhat they receive
Arm A (nivolumab)Active comparatorINDUCTION: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. TREATMENT: Patients with iuPD with clinical instability receive cabozantinib PO daily on days 1-28. Treatment repeats every 28 days until further disease progression or unacceptable toxicity Patients with iCR receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with non-CR/non-PD with clinical stability receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood and urine sample collection, and may also undergo a bone scan as clinically indicated throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Arm B (nivolumab, cabozantinib)ExperimentalINDUCTION: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. TREATMENT: Patients with iuPD with clinical instability receive cabozantinib PO daily on days 1-28. Treatment repeats every 28 days until further disease progression or unacceptable toxicity. Patients with iCR receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with non-CR/non-PD rwith clinical stability eceive nivolumab IV over 30 minutes on day 1 and cabozantinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood and urine sample collection, and may also undergo a bone scan as clinically indicated throughout the study.
Receives: Procedure: Biospecimen Collection; Drug: Cabozantinib; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; 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.

  1. Overall survival (OS)

    OS of patients who achieve complete response (CR) and progressive disease (PD) from ipilimumab-nivolumab induction phase will be summarized. The stratified log-rank statistic will be the primary analysis to compare the hypothesis on OS with the stratification factors (presence of bone metastases and IMDC risk criteria). The Kaplan-Meier product-limit estimator will be used to estimate the OS. A stratified proportional hazards model will be used to generate estimates for the OS hazard ratio. For the randomized patients, OS will be calculated and compared from the time of randomization until the time of an OS event or time of last-follow-up, whatever occurs first. For the patients who were initially CR or PD, OS will be measured from the time of study registration. A comparison of OS will be made across the patient groups (randomized patients, patients initially CR, and patients initially PD).

    Measured: From registration to date of death from any cause for non-randomized patients, from time of randomization until death from any cause for randomized patients, assessed up to 5 years

Secondary outcomes (5)

  1. Progression-free survival (PFS)

    Progression will be defined using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. PFS of patients who achieve CR and PD from ipilimumab-nivolumab induction phase will be summarized (secondary analysis). The Kaplan-Meier product-limit estimator will be used to estimate the PFS distribution. A stratified proportional hazards model will be used to generate estimates for the PFS hazard ratio. For the randomized patients, PFS will be calculated and compared from the time of randomization until the time of a PFS event or time of last-follow-up, whatever occurs first. For the patients who were initially CR or PD, PFS will be measured from the time of study registration. A comparison of PFS will be made across the patient groups (randomized patients, patients initially CR, and patients initially PD). For this comparison, PFS will be measured from time of study registration all the patients, regardless of whether they were randomized or not.

    Measured: From date of registration to date of progression (or disease recurrence) or death due to any cause, whichever occurs first, assessed up to 5 years

  2. Complete response (CR) (randomized patients)

    Patients who had a CR prior to 12 months but have experienced a disease recurrence prior to 12 months, will not be considered to be a CR at 12 months. The Cochran-Mantel-Haenszel test will be used to compare the two arms on the proportion of patients who have a 12-month CR adjusting on the stratification factors.

    Measured: At 12 months from date of randomization

  3. Objective response

    Defined as the best response observed that has been confirmed by a scan performed 4 or more weeks after the observation of the initial response. The objective response will be confirmed using RECIST 1.1. In addition, objective responses will also be confirmed using Immune Response Evaluation Criteria in Solid Tumors (iRECIST).

    Measured: Up to 5 years

  4. Proportion of patients who discontinue protocol-directed treatment prior to 1 year from date of study registration

    Patients who stop their protocol directed treatment for any reason prior to one year from study registration will be considered to have discontinued their treatment. The Cochran-Mantel-Haenszel test will also be used to compare the proportion of patients who discontinue their treatment prior to one-year after study registration.

    Measured: Up to 5 years

  5. Incidence of adverse events

    Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. A Fisher's exact test will be used to compare the two treatment arms on the proportion of patient with a grade 3 or higher adverse event.

    Measured: 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.

  1. First posted4 Jan 2019
  2. Study start7 Jun 2019
  3. Primary completion1 Mar 2028 (estimated)
  4. Study completion1 Mar 2028 (estimated)

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,175 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03793166
Sponsor's protocol ID
NCI-2018-03694
Other IDs
NCI-2018-03694, A031704, A031704, U10CA180821
Status last verified
Oct 2026
First submitted
3 Jan 2019
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Publications

  • Labriola MK, George DJ. Setting a new standard for long-term survival in metastatic kidney cancer. Cancer. 2022 Jun 1;128(11):2058-2060. doi: 10.1002/cncr.34177. Epub 2022 Apr 5. No abstract available.

    PubMed 35383907

  • Yang Y, Psutka SP, Parikh AB, Li M, Collier K, Miah A, Mori SV, Hinkley M, Tykodi SS, Hall E, Thompson JA, Yin M. Combining immune checkpoint inhibition plus tyrosine kinase inhibition as first and subsequent treatments for metastatic renal cell carcinoma. Cancer Med. 2022 Aug;11(16):3106-3114. doi: 10.1002/cam4.4679. Epub 2022 Mar 18.

    PubMed 35304832

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biospecimen Collection, Bone Scan and Cabozantinib in people with Clear Cell Renal Cell Carcinoma and Metastatic Malignant Neoplasm in the Bone, run by National Cancer Institute (NCI) at 859 sites in 2 countries.

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 49 inclusion and 0 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 859 sites in United States, Puerto Rico. 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?

Overall survival (OS) (time frame: From registration to date of death from any cause for non-randomized patients, from time of randomization until death from any cause for randomized patients, 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 NCT03793166, which also lists 2 linked publications.

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.

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