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ACTIVE NOT RECRUITING

NCT03793166

PHASE3

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

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

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. 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.

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]

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

1175

Start Date

2019-06-07

Completion Date

2028-01-25

Last Updated

2026-05-29

Healthy Volunteers

Conditions

Clear Cell Renal Cell Carcinoma Metastatic Malignant Neoplasm in the Bone Metastatic Malignant Neoplasm in the Lymph Nodes Metastatic Malignant Neoplasm in the Soft Tissue Metastatic Malignant Neoplasm in the Viscera Rhabdoid Tumor of the Kidney Sarcomatoid Renal Cell Carcinoma Stage III Renal Cell Cancer AJCC v8 Stage IV Renal Cell Cancer AJCC v8

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood and urine sample collection

PROCEDURE

Bone Scan

Undergo bone scan

DRUG

Cabozantinib

Given PO

PROCEDURE

Computed Tomography

Undergo CT scan

BIOLOGICAL

Ipilimumab

Given IV

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

BIOLOGICAL

Nivolumab

Given IV

OTHER

Quality-of-Life Assessment

Ancillary studies

OTHER

Questionnaire Administration

Ancillary studies

Inclusion Criteria: * 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 * 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

Locations (861)

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, United States

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, United States

Anchorage Radiation Therapy Center

Anchorage, Alaska, United States

Alaska Breast Care and Surgery LLC

Anchorage, Alaska, United States

Alaska Oncology and Hematology LLC

Anchorage, Alaska, United States

Alaska Women's Cancer Care

Anchorage, Alaska, United States

Anchorage Oncology Centre

Anchorage, Alaska, United States

Katmai Oncology Group

Anchorage, Alaska, United States

Providence Alaska Medical Center

Anchorage, Alaska, United States

Fairbanks Memorial Hospital

Fairbanks, Alaska, United States

Kingman Regional Medical Center

Kingman, Arizona, United States

Cancer Center at Saint Joseph's

Phoenix, Arizona, United States

Highlands Oncology Group - Fayetteville

Fayetteville, Arkansas, United States

Mercy Hospital Fort Smith

Fort Smith, Arkansas, United States

CHI Saint Vincent Cancer Center Hot Springs

Hot Springs, Arkansas, United States

Highlands Oncology Group - Rogers

Rogers, Arkansas, United States

Highlands Oncology Group

Springdale, Arkansas, United States

Kaiser Permanente-Anaheim

Anaheim, California, United States

Mission Hope Medical Oncology - Arroyo Grande

Arroyo Grande, California, United States

PCR Oncology

Arroyo Grande, California, United States

Kaiser Permanente-Baldwin Park

Baldwin Park, California, United States

Kaiser Permanente-Bellflower

Bellflower, California, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Community Cancer Institute

Clovis, California, United States

University Oncology Associates

Clovis, California, United States

Kaiser Permanente-Fontana

Fontana, California, United States

Kaiser Permanente South Bay

Harbor City, California, United States

Kaiser Permanente-Irvine

Irvine, California, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Kaiser Permanente West Los Angeles

Los Angeles, California, United States

Kaiser Permanente-Ontario

Ontario, California, United States

Kaiser Permanente - Panorama City

Panorama City, California, United States

Kaiser Permanente-Riverside

Riverside, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Kaiser Permanente-San Diego Mission

San Diego, California, United States

Kaiser Permanente-San Diego Zion

San Diego, California, United States

Sharp Memorial Hospital

San Diego, California, United States

Naval Medical Center -San Diego

San Diego, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Pacific Central Coast Health Center-San Luis Obispo

San Luis Obispo, California, United States

Kaiser Permanente-San Marcos

San Marcos, California, United States

Mission Hope Medical Oncology - Santa Maria

Santa Maria, California, United States

Kaiser Permanente-Woodland Hills

Woodland Hills, California, United States

Rocky Mountain Cancer Centers-Aurora

Aurora, Colorado, United States

The Medical Center of Aurora

Aurora, Colorado, United States

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Boulder Community Foothills Hospital

Boulder, Colorado, United States

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, United States

Rocky Mountain Cancer Centers - Centennial

Centennial, Colorado, United States

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Memorial Hospital North

Colorado Springs, Colorado, United States

Cancer Center of Colorado at Sloan's Lake