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A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment

NCT04338269

Description:

This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of atezolizumab given in combination with cabozantinib versus cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who experienced radiographic tumor progression during or after Immune Checkpoint Inhibitor (ICI) treatment in the metastatic setting.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment
  • Official Title: A Phase III, Multicenter, Randomized, Open-Label 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

Clinical Trial IDs

  • ORG STUDY ID: WO41994
  • NCT ID: NCT04338269

Conditions

  • Carcinoma, Renal Cell

Interventions

DrugSynonymsArms
AtezolizumabTecentriqAtezo+Cabo
CabozantinibCabometyxAtezo+Cabo

Purpose

This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of atezolizumab given in combination with cabozantinib versus cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who experienced radiographic tumor progression during or after Immune Checkpoint Inhibitor (ICI) treatment in the metastatic setting.

Trial Arms

NameTypeDescriptionInterventions
Atezo+CaboExperimentalParticipants will receive atezolizumab every 3 weeks on Day 1 of each 21-day cycle (1 cycle=21 days) plus oral tablets of cabozantinib every day.
  • Atezolizumab
  • Cabozantinib
CabozantinibActive ComparatorParticipants will receive cabozantinib every day.
  • Cabozantinib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed locally advanced or metastatic clear cell or non-clear cell
             (papillary and unclassified only) RCC. RCC with sarcomatoid features is allowed.

          -  Radiographic disease progression during or following treatment with ICI for locally
             advanced or metastatic RCC either in first- or second-line treatment. ICI is defined
             by anti-PD-L1 or anti-PD1 antibody including atezolizumab, avelumab, pembrolizumab, or
             nivolumab. Only patients for whom the immediate preceding line of therapy was an ICI
             are allowed.

          -  Measurable disease per RECIST v1.1

          -  Evaluable IMDC risk score

          -  Archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening,
             if clinically feasible

          -  KPS score of >=70

          -  Adequate hematologic and end-organ function

          -  Negative HIV test at screening

          -  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

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraception and agreement to refrain from donating
             eggs

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             a condom, and agreement to refrain from donating sperm

        Exclusion Criteria:

          -  Treatment with anti-cancer therapy within 28 days prior to initiation of study
             treatment

          -  Patients received cabozantinib at any time prior to screening

          -  Patients who received more than 1 regimen of ICIs

          -  Patients who received more than 2 prior lines of therapy in the advanced or metastatic
             setting

          -  Patients who received ICI in the adjuvant setting (adjuvant VEGFR-TKI except
             cabozantinib is allowed)

          -  Patients who have received a mammalian target of rapamycin (mTOR) inhibitor in the
             advanced or metastatic setting

          -  Symptomatic, untreated, or actively progressing CNS metastases

          -  History of leptomeningeal disease

          -  Uncontrolled 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,
             with the exception of malignancies with a negligible risk of metastasis or death

          -  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 final dose of atezolizumab and 4 months after final dose of
             cabozantinib

          -  Severe infection within 4 weeks prior to initiation of study treatment, including, but
             not limited to, hospitalization for complications of infection, bacteremia, or severe
             pneumonia

          -  Uncontrolled hypertension defined as sustained blood pressure >150 mm Hg systolic or >
             90 mm Hg diastolic despite optimal antihypertensive treatment

          -  Significant cardiovascular disease (such as New York Heart Association Class II or
             greater cardiac disease, MI, or cerebrovascular accident) within 3 months prior to
             initiation of study treatment, unstable arrhythmia, or unstable angina

          -  Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1

          -  History of congenital QT syndrome

          -  History or presence of an abnormal ECG that is clinically significant in the
             investigator's opinion

          -  Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin
             inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors
             (e.g. clopidogrel)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS), as assessed by Independent Review Facility (IRF)
Time Frame:Randomization up to approximately 27 months
Safety Issue:
Description:Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1, as assessed by Independent Review Facility (IRF-PFS) or death from any cause, whichever occurs first.

Secondary Outcome Measures

Measure:PFS Assessed by the Investigators (INV-PFS)
Time Frame:Randomization up to approximately 27 months
Safety Issue:
Description:PFS assessed by the investigators (INV-PFS), defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first).
Measure:Investigator Assessed Objective Response Rate (INV-ORR)
Time Frame:Randomization up to approximately 27 months
Safety Issue:
Description:INV-ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart according to RECIST v1.1.
Measure:IRF Assessed Objective Response Rate (IRF-ORR)
Time Frame:Randomization up to approximately 27 months
Safety Issue:
Description:IRF-ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart according to RECIST v1.1.
Measure:Investigator Assessed Duration of Objective Response (INV-DOR)
Time Frame:Randomization up to approximately 27 months
Safety Issue:
Description:INV-DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) according to RECIST v1.1.
Measure:IRF Assessed DOR (IRF-DOR)
Time Frame:Randomization up to approximately 27 months
Safety Issue:
Description:IRF-DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) according to RECIST v1.1.
Measure:Percentage of Participants With Adverse Events
Time Frame:Randomization up to approximately 27 months
Safety Issue:
Description:
Measure:Atezolizumab Concentrations
Time Frame:At pre-defined intervals from first administration of study drug up to approximately 27 months
Safety Issue:
Description:
Measure:Cabozantinib Concentrations
Time Frame:At pre-defined intervals from first administration of study drug up to approximately 27 months
Safety Issue:
Description:
Measure:Prevalence of Anti-Drug Antibodies (ADAs) to Atezolizumab
Time Frame:Baseline
Safety Issue:
Description:
Measure:Incidence of ADAs to Atezolizumab During the Study
Time Frame:At pre-defined intervals from first administration of study drug up to approximately 27 months
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

June 26, 2020