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

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ClinicalTrials.gov Identifier: NCT02684006
Recruitment Status : Recruiting
First Posted : February 17, 2016
Last Update Posted : January 3, 2018
Sponsor:
Information provided by (Responsible Party):

January 25, 2016
February 17, 2016
January 3, 2018
March 23, 2016
December 2, 2018   (Final data collection date for primary outcome measure)
  • Progression Free Survival (PFS) in PD-L1 positive patients [ Time Frame: From randomization up to 30 months. ]
    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.
  • Overall Survival in PD-L1 positive patients [ Time Frame: Every 3 months up to 5 years ]
    OS is the time from date of randomization to date of death due to any cause.
Progression Free Survival (PFS) [ Time Frame: From randomization up to 30 months. ]
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.
Complete list of historical versions of study NCT02684006 on ClinicalTrials.gov Archive Site
  • Overall Survival (OS) in unselected patients [ Time Frame: Every 3 months up to 5 years ]
    OS is the time from date of randomization to date of death due to any cause.
  • 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 ]
    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)
  • 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 ]
    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.
  • 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 ]
    TRR is the time from randomization to first documentation of objective tumor response (CR or PR).
  • 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 ]
    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
  • 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 ]
    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.
  • Trough plasma concentration (Ctrough) of avelumab [ Time Frame: Pre-dose ]
    Ctrough is defined as the concentration at the end of avelumab dosage interval
  • Trough plasma concentration (Ctrough) of axitinib [ Time Frame: Pre-dose ]
    Ctrough is defined as the concentration at the end of axitinib dosage interval
  • Maximum plasma concentration (Cmax) of axitinib [ Time Frame: 2 hours post-dose ]
    Cmax defined as the maximum plasma concentration of axitinib
  • Anti-Drug Antibody (ADA) levels of avelumab/Neutralizing antibodies titers for MSB0010718C [ Time Frame: Pre-dose ]
    Immunogenicity assessment of avelumab
  • Tumor tissue biomarker status [ Time Frame: Baseline ]
    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
  • Overall Survival (OS) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    OS in biomarker-negative and biomarker-positive subgroups.
  • Change From Baseline in FACT-Kidney Symptom Index (FKSI)-19 [ Time Frame: Every 6 weeks up to 3 years ]
    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.
  • Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Health State Profile [ Time Frame: Every 6 weeks up to 3 years ]
    EQ-5D Health State Profile: participant rated questionnaire to assess health-related quality of life in terms of a single index value.
  • Progression Free Survival (PFS) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    PFS as measure of clinical outcome in biomarker-negative and biomarker-positive subgroups.
  • Objective Response (OR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    OR in biomarker-negative and biomarker-positive subgroups
  • Disease Control (DC) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    DC in biomarker-negative and biomarker-positive subgroups
  • Time To Response (TTR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    TTR in biomarker-negative and biomarker-positive subgroups.
  • Duration of Response (DR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    DR in biomarker-negative and biomarker-positive subgroups.
  • Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Visual Analogic Scale [ Time Frame: Every 6 weeks up to 3 years ]
    EQ-5D Visual Analogic Scale:patients rated their overall health status from 0 (worst imaginable heath state) to 100 (best imaginable heath state).
  • 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 ]
    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
  • Treatment discontinuation/failure due to toxicity [ Time Frame: From Cycle 1 Day 1, every 6 weeks up to the End of Treatment ]
    Treatment discontinuation is the percentage of patients who discontinue the treatment due to an adverse event or death due to study treatment toxicity
  • PFS on next-line therapy (PFS2) [ Time Frame: From randomization up to 5 years. ]
    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.
  • Progression Free Survival (PFS) in unselected patients [ Time Frame: From randomization up to 30 months. ]
    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.
  • Overall Survival (OS) [ Time Frame: Every 3 months up to 5 years ]
    OS is the time from date of randomization to date of death due to any cause.
  • 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 mos from randomization ]
    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)
  • 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 mos from randomization ]
    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.
  • 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 mos from randomization ]
    TRR is the time from randomization to first documentation of objective tumor response (CR or PR).
  • 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 mos from randomization ]
    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
  • 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 mos from randomization ]
    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.
  • Trough plasma concentration (Ctrough) of avelumab [ Time Frame: Pre-dose ]
    Ctrough is defined as the concentration at the end of avelumab dosage interval
  • Trough plasma concentration (Ctrough) of axitinib [ Time Frame: Pre-dose ]
    Ctrough is defined as the concentration at the end of axitinib dosage interval
  • Maximum plasma concentration (Cmax) of axitinib [ Time Frame: 2 hours post-dose ]
    Cmax defined as the maximum plasma concentration of axitinib
  • Anti-Drug Antibody (ADA) levels of avelumab/Neutralizing antibodies titers for MSB0010718C [ Time Frame: Pre-dose ]
    Immunogenicity assessment of avelumab
  • Tumor tissue biomarker status [ Time Frame: Baseline ]
    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
  • Overall Survival (OS) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    OS in biomarker-negative and biomarker-positive subgroups.
  • Change From Baseline in FACT-Kidney Symptom Index (FKSI)-19 [ Time Frame: Every 6 weeks up to 3 years ]
    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.
  • Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Health State Profile [ Time Frame: Every 6 weeks up to 3 years ]
    EQ-5D Health State Profile: participant rated questionnaire to assess health-related quality of life in terms of a single index value.
  • Progression Free Survival (PFS) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    PFS as measure of clinical outcome in biomarker-negative and biomarker-positive subgroups.
  • Objective Response (OR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    OR in biomarker-negative and biomarker-positive subgroups
  • Disease Control (DC) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    DC in biomarker-negative and biomarker-positive subgroups
  • Time To Response (TTR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    TTR in biomarker-negative and biomarker-positive subgroups.
  • Duration of Response (DR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    DR in biomarker-negative and biomarker-positive subgroups.
  • Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Visual Analogic Scale [ Time Frame: Every 6 weeks up to 3 years ]
    EQ-5D Visual Analogic Scale:patients rated their overall health status from 0 (worst imaginable heath state) to 100 (best imaginable heath state).
Not Provided
Not Provided
 
A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)
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
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
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Renal Cell Cancer
  • Drug: Avelumab (MSB0010718C)
    IV treatment Avelumab administered at 10 mg/kg IV every two weeks
  • Drug: Axitinib (AG-013736)
    Oral treatment Axitinib given 5 mg PO BID
    Other Name: Inlyta
  • Drug: Sunitinib
    Oral treatment Sunitinib given at 50 mg PO QD on schedule 4/2
    Other Name: Sutent
  • Experimental: Avelumab in combination with axitinib
    Avelumab administered at 10 mg/kg IV every two weeks in combination with axitinib, 5 mg PO BID.
    Interventions:
    • Drug: Avelumab (MSB0010718C)
    • Drug: Axitinib (AG-013736)
  • Active Comparator: Sunitinib
    Sunitinib given at 50 mg PO QD on schedule 4/2
    Intervention: Drug: Sunitinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
830
April 30, 2021
December 2, 2018   (Final data collection date for primary outcome measure)

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
  • Newly dignosed or active brain metastasis
  • 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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Australia,   Austria,   Belgium,   Canada,   Denmark,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   New Zealand,   Romania,   Russian Federation,   Spain,   Sweden,   United Kingdom,   United States
 
 
NCT02684006
B9991003
2015-002429-20 ( EudraCT Number )
JAVELIN RENAL 101 ( Other Identifier: Alias Study Number )
Yes
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP