This is a randomized, double-blind, controlled trial to evaluate the efficacy and safety of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in previously untreated subjects with intermediate- and poor-risk advanced or metastatic RCC

Phase 1

Conditions: Metastatic Renal Cell Carcinoma
MedDRA version: 20.0Level: LLTClassification code 10050076Term: Metastatic renal carcinomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-004567-31-ES

Lead Sponsor: Exelixis, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 676

Inclusion Criteria

- Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.
- Intermediate- or poor-risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria.
- Measurable disease per RECIST 1.1 as determined by the Investigator.
- Karnofsky Performance Status (KPS) = 70%.
- Adequate organ and marrow function.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 418
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 258

Exclusion Criteria

- Prior systemic therapy for unresectable locally advanced or metastatic RCC including investigational agents.
- Uncontrolled, significant intercurrent or recent illness including, but not limited to serious cardiovascular disorders (including uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment), GI disorders associated with high risk for perforation or fistula formation, tumors invading GI tract, bowel obstruction, intra-abdominal abscess, clinically significant bleeding events, cavitating pulmonary lesions, or lesion invading major pulmonary blood vessels.
-Other clinically significant disorders such as:
i. Any active, known or suspected autoimmune disease.
ii. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization.
iii. Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired
immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection.
-Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to randomization. Prior laparoscopic nephrectomy within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major surgery or minor surgery before randomization.
- Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this study is to evaluate the efficacy and safety of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in previously untreated subjects with intermediate- and poor-risk advanced or metastatic RCC.;Secondary Objective: Not applicable;Primary end point(s): Duration of PFS (Progression-Free Survival), per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC);Timepoint(s) of evaluation of this end point: The first tumor assessment after randomization should be performed at W10D1 (± 7 days). Subsequent tumor assessments should be performed every 8 weeks (± 7 days) from randomization through Week 50. Upon completion of 50 weeks on study, these assessments will be performed every 12 weeks (± 7 days). Additional imaging of potential disease sites should be performed whenever radiographic PD is suspected.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Duration of OS (overall survival);Timepoint(s) of evaluation of this end point: Overall survival (OS) will continue to be assessed every 12 weeks (± 14 days) after the second post-treatment follow-up visit (FU-2), which occurs 100 (±14) days after discontinuation of study treatment. Subjects will be followed until death or Sponsor decision to no longer collect these data

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