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

Running, not enrolling · Phase 3

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT03793166

Run by

National Cancer Institute (NCI)

People needed

1175

Starts

2019-06-07

Expected to finish

2028-01-25

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

Where it is running

• 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
• University of South Alabama Mitchell Cancer Institute — Mobile, Alabama, United States

Full record on ClinicalTrials.gov

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