Clinical Trials /

A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy

NCT03024996

Description:

This is a Phase III, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of atezolizumab versus placebo in participants with RCC who are at high risk of disease recurrence following nephrectomy.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy
  • Official Title: A Phase III, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Atezolizumab (Anti−PD-L1 Antibody) as Adjuvant Therapy in Patients With Renal Cell Carcinoma at High Risk of Developing Metastasis Following Nephrectomy

Clinical Trial IDs

  • ORG STUDY ID: WO39210
  • SECONDARY ID: 2016-001881-27
  • NCT ID: NCT03024996

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
AtezolizumabAtezolizumab

Purpose

This is a Phase III, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of atezolizumab versus placebo in participants with RCC who are at high risk of disease recurrence following nephrectomy.

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalParticipants will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion every 3 weeks (q3w) for 16 cycles (each cycle=21 days) or 1 year (whichever occurs first).
  • Atezolizumab
PlaceboPlacebo ComparatorParticipants will receive placebo matching to atezolizumab q3w for 16 cycles (each cycle=21 days) or 1 year (whichever occurs first).

    Eligibility Criteria

            Inclusion Criteria:
    
              -  ECOG performance status of less than or equal to (</=) 1
    
              -  Pathologically confirmed RCC with a component of either clear cell histology or
                 sarcomatoid histology that has not been previously treated in the adjuvant or
                 neoadjuvant setting and classified as being at high risk of RCC recurrence
    
              -  Radical or partial nephrectomy with lymphadenectomy in select participants
    
              -  Absence of residual disease and absence of metastasis, as confirmed by a negative
                 baseline computed tomography (CT) of the pelvis, abdomen, and chest no more than 4
                 weeks prior to randomization.
    
              -  Absence of brain metastasis, as confirmed by a negative CT with contrast or magnetic
                 resonance imaging (MRI) scan of the brain, no more than 4 weeks prior to
                 randomization. Applicable only to metastasectomy participants
    
              -  Full recovery from nephrectomy or metastasectomy within 12 weeks from randomization
                 following surgery
    
            Exclusion Criteria:
    
              -  Bilateral synchronous tumors with inheritable forms of RCC including von
                 Hippel-Lindau
    
              -  Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within
                 3 weeks prior to initiation of study treatment
    
              -  Treatment with any other investigational agent or participation in another clinical
                 study with therapeutic intent within 28 days or five half-lives of the
                 investigational agent, whichever is longer, prior to enrollment
    
              -  Malignancies other than RCC within 5 years prior to Cycle 1, Day 1
    
              -  Participants with prior allogeneic stem cell or solid organ transplantation
    
              -  History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
                 pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
                 organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
    
              -  Positive test for HIV
    
              -  Participants with active hepatitis B or hepatitis C
    
              -  Active tuberculosis
    
              -  Severe infections within 4 weeks prior to randomization including but not limited to
                 hospitalization for complications of infection, bacteremia, or severe pneumonia
    
              -  Major surgical procedure within 4 weeks prior to randomization or anticipation of
                 need for a major surgical procedure during the course of the study other than for
                 diagnosis
    
              -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
    
              -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
                 laboratory finding giving reasonable suspicion of a disease or condition that
                 contraindicates the use of an investigational drug or that may affect the
                 interpretation of the results or render the participant at high risk from treatment
                 complications
    
              -  Prior treatment with cluster of differentiation (CD)137 agonists, anti-cytotoxic
                 T-lymphocyte-associated protein-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD−1),
                 or anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibody or
                 pathway-targeting agents
    
              -  Treatment with systemic immunostimulatory agents (including but not limited to
                 interferons or interleukin-2) within 6 weeks or five half-lives of the drug,
                 whichever is shorter, prior to randomization
    
              -  Treatment with systemic immunosuppressive medications (including but not limited to
                 corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
                 anti−tumor necrosis factor agents) within 2 weeks prior to randomization or
                 anticipated need for systemic immunosuppressive medications during the study
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Disease-Free Survival (DFS)
    Time Frame:From Baseline until first occurrence of DFS event (up to approximately 64 months)
    Safety Issue:
    Description:DFS is defined as the time from randomization to the first documented DFS event. DFS event includes any of the following: Local recurrence of RCC, New primary RCC, Distant metastasis of RCC, or Death from any cause. Tumor assessment will be as per investigator on the basis of radiographic evidence and whenever possible supported/confirmed by biopsy results.

    Secondary Outcome Measures

    Measure:Overall Survival
    Time Frame:From Baseline up to death due to any cause (up to approximately 88 months)
    Safety Issue:
    Description:
    Measure:DFS in Participants With Tumor-Infiltrating Immune Cell (IC) 1/2/3
    Time Frame:From Baseline until first occurrence of DFS event (up to approximately 88 months)
    Safety Issue:
    Description:DFS is defined as the time from randomization to the first documented DFS event. DFS event includes any of the following: Local recurrence of RCC, New primary RCC, Distant metastasis of RCC, or Death from any cause. Tumor assessment will be as per investigator on the basis of radiographic evidence and whenever possible supported/confirmed by biopsy results.
    Measure:Disease-Specific Survival
    Time Frame:From Baseline up to death due to RCC (up to approximately 88 months)
    Safety Issue:
    Description:
    Measure:Distant Metastasis-Free Survival
    Time Frame:From Baseline up to date of diagnosis of distant metastases or death due to any cause (up to approximately 88 months)
    Safety Issue:
    Description:
    Measure:Percentage of Participants Who Are Alive and Recurrence Free at Year 3
    Time Frame:Year 3
    Safety Issue:
    Description:Recurrence assessment will be as per investigator on the basis of radiographic evidence and whenever possible supported/confirmed by biopsy results.
    Measure:Percentage of Participants With Adverse Events
    Time Frame:From Baseline up to 90 days after last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (last dose = up to approximately 1 year)
    Safety Issue:
    Description:
    Measure:Maximum Serum Concentration (Cmax) of Atezolizumab
    Time Frame:Predose (Hour[hr]0), 0.5 hr after end of infusion (infusion duration=1 hr) on Cycle 1 Day 1; predose (hr 0) on Day 1 of Cycles 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days)
    Safety Issue:
    Description:
    Measure:Minimum Serum Concentration (Cmin) of Atezolizumab
    Time Frame:Predose (Hour[hr]0), 0.5 hr after end of infusion (infusion duration=1 hr) on Cycle 1 Day 1; predose (hr 0) on Day 1 of Cycles 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days)
    Safety Issue:
    Description:
    Measure:Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab
    Time Frame:Predose (hr 0) on Day 1 of Cycles 1, 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days)
    Safety Issue:
    Description:

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Hoffmann-La Roche

    Last Updated

    April 4, 2017