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: PTClassification code 10073251Term: Clear cell renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000502-29-IT
- Lead Sponsor
- F. HOFFMANN - 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 (RCC with sarcomatoid features is allowed)
• 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. Only patients for whom the immediate preceding line of therapy was an ICI are allowed. ICI is defined by anti¿PD-L1 or anti¿PD1 antibody including atezolizumab, avelumab, pembrolizumab, 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 score
• Two representative pretreatment tumor specimen for exploratory biomarker research: archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening, if clinically feasible.
• Karnofsky Performance Status score of >= 70
• 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
•Treat with anti-cancer therapy within 28d prior to initiation of study treatment•Pz received cabozantinib (Cabo) at any time prior to screening•Pz who received more than 1 regimen of ICIs•Pz who received more than 2 prior lines of therapy in the advanced or metastatic setting•Pz who received ICI in the adjuvant setting•Pz who have received a mammalian target of rapamycin inhibitor in the advanced or metastatic setting•Symptomatic, untreated, or actively progressing CNS metastases•History of leptomeningeal disease•Uncontrolled tumor-related pain, 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•Active tuberculosis•Major surgical procedure, other than for diagnosis, within 4w 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 5m after the final dose of atezolizumab (Atezo) and 4m after the final dose of Cabo•Severe infection within 4w prior to initiation of study treatment•Treat with systemic immunostimulatory agents within 4w or 5 drug-elimination half-lives prior to initiation of study treat•Treat with systemic immunosuppressive medication within 2w prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment•Treat with therapeutic oral or IV antibiotics within 2w prior to initiation of study treat•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 treat with anti-viral therapy for HBV or HCV •Active or history of autoimmune disease or immune deficiency•History of idiopathic pulmonary fibrosis,organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan•Pat with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption•Uncontrolled hypertension defined as sustained blood pressure (BP)>150mmHg systolic or>90mmHg diastolic despite optimal antihypertensive treat•Stroke,myocardial infarction (MI), or other symptomatic ischemic event,or thromboembolic event within 6m before first dose•cardiovascular disease within 3m prior to initiation of study treatment, unstable arrhythmia, or unstable angina•History of clinically significant ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease,coronary heart disease,clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome•History of congenital QTsyndrome•History or presence of an abnormal ECG that is clinically significant in the investigator's opinion•QTinterval corrected through use of Fridericia's formula>48 ms per ECG within 14 d before randomiz•Significant vascular disease within 6 m prior to D1 of C1•Evidence of bleeding diathesis or significant coagulopathy•History abdominal or tracheoesophageal fistula or gastroint perfor within 6 m prior to D1 of C1•Concom anticoagula
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of atezolizumab in combination with cabozantinib (i.e. atezolizumab + cabozantinib arm) compared with cabozantinib alone (cabozantinib arm) in the intention-to-treat population;Secondary Objective: • To evaluate the efficacy of atezolizumab in combination with cabozantinib compared with cabozantinib alone in the intent-to-treat population<br>• To evaluate the safety of atezolizumab in combination with cabozantinib compared with cabozantinib alone in the intent-to-treat population<br>• To characterize the pharmacokinetics profile of atezolizumab and cabozantinib administered in combination<br>• To evaluate the immune response to atezolizumab (for atezolizumab+ cabozantinib arm)<br>;Primary end point(s): 1. Progression-free survival as assessed by Independent Review Facility (IRF)<br>2. Overall survival ;Timepoint(s) of evaluation of this end point: 1. Approximately 55 months
- Secondary Outcome Measures
Name Time Method