Clinical Trials /

A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)

NCT02684006

Description:

This is a phase 3 randomized trial evaluating the anti-tumor activity and safety of avelumab in combination with axitinib and of sunitinib monotherapy, administered as first-line treatment, in patients with advanced renal cell carcinoma

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)
  • Official Title: A Phase 3, Multinational, Randomized, Open-label, Parallel-arm Study Of Avelumab (msb0010718c) In Combination With Axitinib (Inlyta(Registered)) Versus Sunitinib (Sutent(Registered)) Monotherapy In The First-line Treatment Of Patients With Advanced Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: B9991003
  • SECONDARY ID: 2015-002429-20
  • SECONDARY ID: JAVELIN RENAL 101
  • NCT ID: NCT02684006

Conditions

  • Renal Cell Cancer

Interventions

DrugSynonymsArms
Avelumab (MSB0010718C)Avelumab in combination with axitinib
Axitinib (AG-013736)InlytaAvelumab in combination with axitinib
SunitinibSutentSunitinib

Purpose

This is a phase 3 randomized trial evaluating the anti-tumor activity and safety of avelumab in combination with axitinib and of sunitinib monotherapy, administered as first-line treatment, in patients with advanced renal cell carcinoma

Trial Arms

NameTypeDescriptionInterventions
Avelumab in combination with axitinibExperimentalAvelumab administered at 10 mg/kg IV every two weeks in combination with axitinib, 5 mg PO BID.
  • Avelumab (MSB0010718C)
  • Axitinib (AG-013736)
SunitinibActive ComparatorSunitinib given at 50 mg PO QD on schedule 4/2
  • Sunitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed advanced or metastatic RCC with clear cell
             component

          -  Availability of a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a
             de novo tumor biopsy during screening (biopsied tumor lesion should not be a RECIST
             target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block
             (not cut slides) from a primary or metastatic tumor resection or biopsy can be
             provided if the following criteria are met: 1) the biopsy or resection was performed
             within 1 year of randomization AND 2) the patient has not received any intervening
             systemic anti-cancer treatment from the time the tissue was obtained and randomization
             onto the current study. If an FFPE tissue block cannot be provided as per documented
             regulations then, 15 unstained slides (10 minimum) will be acceptable

          -  Availability of an archival FFPE tumor tissue from primary tumor resection specimen
             (if not provided per above). If an FFPE tissue block cannot be providedas per
             documented regulations 15 unstained slides (10 minimum) will be acceptable

          -  At least one measureable lesion as defined by RECIST version 1.1 that has not been
             previously irradiated.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Adequate bone marrow function, renal and liver functions

        Exclusion Criteria:

          -  Prior systemic therapy directed at advanced or metastatic RCC.

          -  Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has
             occurred during or within 12 months after the last dose of treatment

          -  Prior immunotherapy with IL-2, IFN-α, or anti PD 1, anti PD L1, anti PD L2, anti
             CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody
             (including ipilimumab), or any other antibody or drug specifically targeting T cell co
             stimulation or immune checkpoint pathways

          -  Prior therapy with axitinib and/or sunitinib as well as any prior therapies with other
             VEGF pathway inhibitors.

          -  Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any
             history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially
             controlled asthma Global Initiative for Asthma 2011).

          -  Any of the following in the previous 12 months: myocardial infarction, severe/unstable
             angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
             LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular
             accident, transient ischemic attack.

          -  Any of the following in the previous 6 months: deep vein thrombosis or symptomatic
             pulmonary embolism.

          -  Vaccination within 4 weeks of the first dose of avelumab and while on trial is
             prohibited except for administration of inactivated vaccines (for example, inactivated
             influenza vaccines).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:From randomization up to 30 months.
Safety Issue:
Description:Progression Free Survival (PFS) is the time from randomization to date of first documentation of objective progression of disease assessed by BICR (by RECIST version 1.1) or death due to any cause.

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Every 3 months up to 5 years
Safety Issue:
Description:OS is the time from date of randomization to date of death due to any cause.
Measure:Number of participants with Objective Response (OR)
Time Frame:Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 30 months from randomization
Safety Issue:
Description:Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1 recorded from randomization until disease progression assessed by BICR or death due to any cause)
Measure:Disease Control (DC)
Time Frame:Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 30 months from randomization
Safety Issue:
Description:DC is defined as complete response (CR), partial response (PR), or stable disease (SD) according to the RECIST v.1.1 recorded from randomization until disease progression assessed by BICR or death due to any cause.
Measure:Time to Tumor Response (TTR)
Time Frame:Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 30 months from randomization
Safety Issue:
Description:TRR is the time from randomization to first documentation of objective tumor response (CR or PR).
Measure:Duration of response (DR)
Time Frame:Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 30 months from randomization
Safety Issue:
Description:DR is the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression assessed by BICR or death due to any cause
Measure:Progression Free Survival (PFS) by Investigator assessment
Time Frame:Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 30 months from randomization
Safety Issue:
Description:Progression Free Survival (PFS) is the time from randomization to date of first documentation of objective progression of disease assessed by the Investigator (by RECIST version 1.1) or death due to any cause.
Measure:Trough plasma concentration (Ctrough) of avelumab
Time Frame:Pre-dose
Safety Issue:
Description:Ctrough is defined as the concentration at the end of avelumab dosage interval
Measure:Trough plasma concentration (Ctrough) of axitinib
Time Frame:Pre-dose
Safety Issue:
Description:Ctrough is defined as the concentration at the end of axitinib dosage interval
Measure:Maximum plasma concentration (Cmax) of axitinib
Time Frame:2 hours post-dose
Safety Issue:
Description:Cmax defined as the maximum plasma concentration of axitinib
Measure:Anti-Drug Antibody (ADA) levels of avelumab/Neutralizing antibodies titers for MSB0010718C
Time Frame:Pre-dose
Safety Issue:
Description:Immunogenicity assessment of avelumab
Measure:Tumor tissue biomarker status
Time Frame:Baseline
Safety Issue:
Description:Biomarker status defined as positive or negative based on a pre-specified scoring algorithm involving, for example, PD-L1 expression and/or quantitation of tumor infiltrating CD8+T lymphocytes as assessed by IHC
Measure:Overall Survival (OS) in biomarker-positive and biomarker-negative subgroups
Time Frame:Baseline
Safety Issue:
Description:OS in biomarker-negative and biomarker-positive subgroups.
Measure:Change From Baseline in FACT-Kidney Symptom Index (FKSI)-19
Time Frame:Every 6 weeks up to 3 years
Safety Issue:
Description:The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains- Disease Related Symptoms (physical and emotional), Treatment related side effects and Functional and Well-Being . A negative change from Baseline represents a worsening of condition.
Measure:Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Health State Profile
Time Frame:Every 6 weeks up to 3 years
Safety Issue:
Description:EQ-5D Health State Profile: participant rated questionnaire to assess health-related quality of life in terms of a single index value.
Measure:Progression Free Survival (PFS) in biomarker-positive and biomarker-negative subgroups
Time Frame:Baseline
Safety Issue:
Description:PFS as measure of clinical outcome in biomarker-negative and biomarker-positive subgroups.
Measure:Objective Response (OR) in biomarker-positive and biomarker-negative subgroups
Time Frame:Baseline
Safety Issue:
Description:OR in biomarker-negative and biomarker-positive subgroups
Measure:Disease Control (DC) in biomarker-positive and biomarker-negative subgroups
Time Frame:Baseline
Safety Issue:
Description:DC in biomarker-negative and biomarker-positive subgroups
Measure:Time To Response (TTR) in biomarker-positive and biomarker-negative subgroups
Time Frame:Baseline
Safety Issue:
Description:TTR in biomarker-negative and biomarker-positive subgroups.
Measure:Duration of Response (DR) in biomarker-positive and biomarker-negative subgroups
Time Frame:Baseline
Safety Issue:
Description:DR in biomarker-negative and biomarker-positive subgroups.
Measure:Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Visual Analogic Scale
Time Frame:Every 6 weeks up to 3 years
Safety Issue:
Description:EQ-5D Visual Analogic Scale:patients rated their overall health status from 0 (worst imaginable heath state) to 100 (best imaginable heath state).
Measure:Time to treatment discontinuation/failure due to toxicity (TTF)
Time Frame:From Cycle 1 Day 1, every 6 weeks up to the End of Treatment
Safety Issue:
Description:TTF is defined as the time from Cycle 1 Day 1 to the date of the first documentation of discontinuation due to an adverse event or death due to study treatment toxicity
Measure:Treatment discontinuation/failure due to toxicity
Time Frame:From Cycle 1 Day 1, every 6 weeks up to the End of Treatment
Safety Issue:
Description:Treatment discontinuation is the percentage of patients who discontinue the treatment due to an adverse event or death due to study treatment toxicity
Measure:PFS on next-line therapy (PFS2)
Time Frame:From randomization up to 5 years.
Safety Issue:
Description:PFS2 is defined as the time from randomization to discontinuation of next line treatment, second objective disease progression, or death from any cause, whichever occurs first.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Cancer
  • renal cell cancer
  • kidney disease
  • kidney neoplasms
  • axitinib, sunitinib

Last Updated

July 24, 2017