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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 : Active, not recruiting
First Posted : February 17, 2016
Last Update Posted : December 22, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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Brief Summary:
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

Condition or disease Intervention/treatment Phase
Renal Cell Cancer Drug: Avelumab (MSB0010718C) Drug: Axitinib (AG-013736) Drug: Sunitinib Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 888 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 23, 2016
Actual Primary Completion Date : August 31, 2023
Estimated Study Completion Date : May 21, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Avelumab in combination with axitinib
Avelumab administered at 10 mg/kg IV every two weeks in combination with axitinib, 5 mg PO BID.
 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
Active Comparator: Sunitinib
Sunitinib given at 50 mg PO QD on schedule 4/2
 Drug: Sunitinib
Oral treatment Sunitinib given at 50 mg PO QD on schedule 4/2
Other Name: Sutent


Outcome Measures
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Primary Outcome Measures :
  1. Progression Free Survival (PFS) in PD-L1 positive patients [ Time Frame: From randomization up to 40 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.

  2. Overall Survival in PD-L1 positive patients [ Time Frame: Every 3 months up to 8 years ]
    OS is the time from date of randomization to date of death due to any cause.


Secondary Outcome Measures :
  1. Overall Survival (OS) in unselected patients [ Time Frame: Every 3 months up to 8 years ]
    OS is the time from date of randomization to date of death due to any cause.

  2. 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 40 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)

  3. Disease Control (DC) [ Time Frame: Every 6 weeks up to 18 months from patient enrollment in the study, then every 12 weeks up to 40 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.

  4. 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 40 months from randomization ]
    TRR is the time from randomization to first documentation of objective tumor response (CR or PR).

  5. 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 40 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

  6. 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 40 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.

  7. Trough plasma concentration (Ctrough) of avelumab [ Time Frame: Pre-dose ]
    Ctrough is defined as the concentration at the end of avelumab dosage interval

  8. Trough plasma concentration (Ctrough) of axitinib [ Time Frame: Pre-dose ]
    Ctrough is defined as the concentration at the end of axitinib dosage interval

  9. Maximum plasma concentration (Cmax) of axitinib [ Time Frame: 2 hours post-dose ]
    Cmax defined as the maximum plasma concentration of axitinib

  10. Anti-Drug Antibody (ADA) levels of avelumab/Neutralizing antibodies titers for MSB0010718C [ Time Frame: Pre-dose ]
    Immunogenicity assessment of avelumab

  11. 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

  12. Overall Survival (OS) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    OS in biomarker-negative and biomarker-positive subgroups.

  13. Change From Baseline in FACT-Kidney Symptom Index (FKSI)-19 [ Time Frame: Every 6 weeks up to 8 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.

  14. Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Health State Profile [ Time Frame: Every 6 weeks up to 8 years ]
    EQ-5D Health State Profile: participant rated questionnaire to assess health-related quality of life in terms of a single index value.

  15. 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.

  16. Objective Response (OR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    OR in biomarker-negative and biomarker-positive subgroups

  17. Disease Control (DC) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    DC in biomarker-negative and biomarker-positive subgroups

  18. Time To Response (TTR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    TTR in biomarker-negative and biomarker-positive subgroups.

  19. Duration of Response (DR) in biomarker-positive and biomarker-negative subgroups [ Time Frame: Baseline ]
    DR in biomarker-negative and biomarker-positive subgroups.

  20. Change from Baseline in European Quality of Life Questionnaire (EQ-5D) - Visual Analogic Scale [ Time Frame: Every 6 weeks up to 8 years ]
    EQ-5D Visual Analogic Scale:patients rated their overall health status from 0 (worst imaginable heath state) to 100 (best imaginable heath state).

  21. 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

  22. 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

  23. PFS on next-line therapy (PFS2) [ Time Frame: From randomization up to 8 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.

  24. Progression Free Survival (PFS) in unselected patients [ Time Frame: From randomization up to 40 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02684006


Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02684006    
Other Study ID Numbers: B9991003
2015-002429-20 ( EudraCT Number )
JAVELIN RENAL 101 ( Other Identifier: Alias Study Number )
First Posted: February 17, 2016    Key Record Dates
Last Update Posted: December 22, 2023
Last Verified: December 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Keywords provided by Pfizer:
Cancer
renal cell cancer
kidney disease
kidney neoplasms
axitinib, sunitinib
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
 Male Urogenital Diseases
Sunitinib
Avelumab
Axitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological