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Protocol No. A031704

Principal Investigator Emamekhoo, Hamid

Phase III

Age Group Adult

Scope National

Sponsor Type National

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]

Objective The purpose of this study is to compare the usual treatment alone (treatment with ipilimumab and nivolumab followed by nivolumab alone) to the usual treatment with ipilimumab and nivolumab, followed by nivolumab with cabozantinib. This study will help the study doctors find out if this different approach is better than the usual approach. These treatments (ipilimumab and nivolumab combination treatment, and cabozantinib treatment alone) are already approved by the FDA for use in advanced kidney cancer which has not been previously treated, but the combination of all three drugs is not FDA approved

Treatment
Step 1: Induction: Ipi + Nivo for 4 cycles
Step 2:
  • CR: Nivo every 28 days for up to 1 year
  • Non CR/Non PD: Arm A: Nivo every 28 days until PD, Arm B: Cabozantinib orally until PD
  • PD: Cabozantinib orally until further progression

  • Description Phase III Trial of Nivolumab + Ipilimumab followed by Nivolumab versus Cabozantinib + Nivolumab for metastatic untreated RCC

    Key Eligibility
  • Histologically documented renal cell carcinoma with clear cell component, including patients who have sarcomatoid features
  • Any metastatic disease, including visceral, lymph node, other soft tissue and bone,measurable per RECIST 1.1
  • CNS disease permitted, if stable and not otherwise causing symptoms or needing active treatment
  • Karnofsky performance status greater than or equal to 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 Tcell co-stimulation or checkpoint pathways
  • No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 (greater than 28 days) and prior adjuvant sunitinib greater than 180 days since completion are allowed)
  • Can not be pregnant or breastfeeding
  • Male and Female of childbearing potential must agree to adequate birth control as defined by the protocol
  • 18 years of age or older
  • Adequate hematologic, renal and hepatic function as defined by the protocol
    EXCLUSION
  • Active autoimmune disease requiring ongoing therapy
  • History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
  • History of HIV or active hepatitis B/C, or tuberculosis
  • Concurrent use of immunosuppressive medication including prednisone above 10 mg daily
  • Uncontrolled adrenal insufficiency
  • Serious non-healing wound, ulcer, or bone fracture within 28 days prior to registration
  • Uncontrolled hypertension
  • 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
  • Moderate of severe hepatic impairment (child-Pugh B or C)
  • History of untreated pulmonary embolism or deep venous thrombosis (DVT) in the 180 days prior to registration
  • Corrected QT interval calculated by the Fridericia formula (QTcF) greater than 500 ms
  • Unstable cardiac arrhythmia within 6 months 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, evidence of pancreatitis, history of organ transplant, or history of congenital QT syndrome
  • Active treatment with warfarin or any oral factor Xa inhibitors (treatment with LMWH is allowed)
  • Significant cardiac ischemia events (STEMI or NSTEMI) within 6 months or active NY Heart Association Class 3-4 heart failure symptoms
    Step 2 registration: Successful completion of at least 1 cycle of ipilimumab/nivolumab, no more than 56 days from last dose of ipilimumab/nivolumab

  • Applicable Disease Sites Kidney

    Status Open

    Participating Institutions Dean Health System, Hematology and Oncology Clinic ; UW Hospital and Clinics; UWCCC 1 South Park