A Study to Evaluate the Efficacy and Safety of Atezolizumab Given in Combination with Cabozantinib Versus Cabozantinib Alone in Patients with Inoperable, Locally Advanced, or Metastatic Renal Cell Carcinoma who Experienced Radiographic Tumor Progression During or After Immune Checkpoint Inhibitor Treatment
- Conditions
- Renal cell carcinoma (RCC)MedDRA version: 21.0Level: LLTClassification code 10038395Term: Renal carcinomaSystem Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10038400Term: Renal carcinoma stage IVSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10050076Term: Metastatic renal carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000502-29-DE
- Lead Sponsor
- F. Hoffman-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 500
• Age >= 18 years
• Histologically confirmed locally advanced or metastatic clear cell or non-clear cell RCC (papillary, chromophobe and unclassified only). RCC with sarcomatoid features is allowed. Patients with the chromophobe subtype of non-clear cell RCC must have sarcomatoid differentiation
• Radiographic disease progression during or following treatment with immune checkpoint inhibitors (ICI) for locally advanced or metastatic RCC either in first-or second-line treatment. Patients who experienced radiographic tumor progression during or within 6 months after the last dose of adjuvant ICI are also eligible. Patients must have received at least 2 cycles of ICI treatment . ICI must have been used in the immediate preceding line of therapy. ICI is defined by anti PD-L1 or anti PD1 antibody including atezolizumab, avelumab, pembrolizumab, durvalumab or nivolumab. Ipilimumab monotherapy is not considered
an anti PD-L1 or anti PD1 therapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1
• Evaluable International Metastatic Renal Cell Carcinoma Database Consortium risk scores
• Representative pretreatment tumor specimen for exploratory biomarker research: archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening, if clinically feasible. Both archival and fresh samples are preferred.
• Karnofsky Performance Status score of >= 70
• Recovery to baseline or Grade <=1 National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable in the opinion of the investigator. Grade 2 alopecia is allowed for study participation
• Adequate hematologic and end-organ function
• Negative hepatitis B testing at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
• Negative HIV test at screening
• For women of childbearing potential: agreement to remain abstinent or use contraception and agree to refrain from donating eggs for 4 months after the final dose of cabozantinib and for 5 months after the final dose of atezolizumab
• For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm for 4 months after the final dose of cabozantinib to avoid exposing the embryo
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 275
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 225
• Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment
• Patients who received cabozantinib at any time prior to screening
• Patients who received more than one ICI treatment in the locally advanced or metastatic setting
• Patients who received more than two prior lines of therapy in the locally advanced or metastatic setting
• Patients who have received a mammalian target of rapamycin inhibitor in any setting
• Symptomatic, untreated, or actively progressing CNS metastases
• History of leptomeningeal disease
• Uncontrolled tumor-related pain or pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• History of malignancy other than renal carcinoma within 5 years prior to screening
• Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1
• Active tuberculosis
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab and 4 months after the final dose of cabozantinib
• Severe infection within 4 weeks prior to initiation of study treatment, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia or any active infection that, in the opinion of the investigator, could impact patient safety
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Prior allogeneic stem cell or solid organ transplantation
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Current treatment with anti-viral therapy for HBV or HCV
• Active or history of autoimmune disease or immune deficiency
• Pharmacologically uncompensated, symptomatic hypothyroidism
• Malabsorption syndrome
• Uncontrolled hypertension
• Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease
• Stroke, myocardial infarction, or other symptomatic ischemic event, or thromboembolic event within 6 months before first dose randomization
• Significant cardiovascular disease within 3 months prior to initiation of study treatment
• History of clinically significant ventricular dysrhythmias or risk factors for ventricular dysrhythmias or congenital QT syndrome
• History or presence of an abnormal ECG that is clinically significant
• Concomitant anticoagulation with coumarin agents, direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platele
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method