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A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)

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ClinicalTrials.gov Identifier: NCT02493751
Recruitment Status : Active, not recruiting
First Posted : July 9, 2015
Last Update Posted : December 21, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE July 7, 2015
First Posted Date  ICMJE July 9, 2015
Last Update Posted Date December 21, 2018
Actual Study Start Date  ICMJE October 15, 2015
Actual Primary Completion Date April 3, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 7, 2015)
Number of participant with Dose-Limiting Toxicities (DLT) [ Time Frame: First 4 weeks of treatment ]
DLTs of avelumab in combination with axitinib occurred during the first 4 weeks of treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02493751 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2018)
  • Number of participants with Objective Response [ Time Frame: Every 6 weeks up to 1 year from start date, then every 12 weeks ]
    Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1) from the start date until disease progression or death due to any cause.
  • Duration of response (DR) [ Time Frame: Every 6 weeks up to 1 year from start date, then every 12 weeks ]
    DR is the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause.
  • Progression Free Survival (PFS) [ Time Frame: Every 6 weeks up to 1 year from start date, then every 12 weeks ]
    Progression Free Survival (PFS) is the time from the start date to the date of the first documentation of objective progression of disease (PD) or death due to any cause.
  • Time to Response (TTR) [ Time Frame: Every 6 weeks up to 1 year from start date, then every 12 weeks ]
    Time to Tumor Response (TTR) is the time from start date to the first documentation of objective tumor response (CR or PR) that is subsequently confirmed.
  • Maximum plasma concentration (Cmax) of MSB0010718C (avelumab) [ Time Frame: 1 hour post-dose ]
    Cmax defined as the maximum plasma concentration of MSB0010718C (avelumab)
  • Maximum plasma concentration (Cmax) of axitinib [ Time Frame: 1, 2, 3, 4 hours post-dose ]
    Cmax defined as the maximum plasma concentration of axitinib
  • Time to reach the maximum plasma concentration (Tmax) of axitinib [ Time Frame: 1, 2, 3, 4 hours post-dose ]
    Tmax is the time needed to reach the maximum plasma concentration of axitinib
  • Trough plasma concentration (Ctrough) of MSB0010718C (avelumab) [ Time Frame: 0 hour (pre-dose) ]
    Ctrough is defined as the concentration at the end of MSB0010718C (avelumab) dosage interval
  • AUC0-tau is the area under the curve from time 0 to next dose for axitinib [ Time Frame: 0, 1, 2, 3, 4, 6, 8 hours post-dose ]
    AUC0-tau is area under the concentration-time curve from time 0 to next dose for axitinib
  • Elimination half-life (t1/2) of axitinib [ Time Frame: 0, 1, 2, 3, 4, 6, 8 hours post-dose ]
    T1/2 is defined as the time required for the concentration of axitinib to reach half of its original value
  • Tumor tissue biomarkers [ 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
  • Anti-Drug Antibody (ADA) levels of MSB0010718C/Neutralizing antibodies titers for MSB0010718C [ Time Frame: Every 2 weeks up to week 7, every 4 weeks up to week 15, then Q12W until week 101 and at 30 Days after the last avelumab administration ]
    Immunogenicity assessment of MSB0010718C
  • Disease Control (DC) [ Time Frame: Every 6 weeks up to 1 year from start date, then every 12 weeks ]
    Disease Control is defined as OR (CR or PR) or stable disease (SD) per RECIST v1.1 from the start date until the first documentation of objective disease progression or death due to any cause.
  • Overall Survival [ Time Frame: Every 30 days (up to 90 days after the last administration) and then every 3 months up to 5 years ]
    Overall survival (OS) is the time from the start date to the date of death due to any cause.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2015)
  • Number of participants with Objective Response [ Time Frame: Every 6 weeks up to 1 year from patient enrollment in the study, then every 12 weeks ]
    Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1).
  • Duration of response (DR) [ Time Frame: Every 6 weeks up to 1 year from patient enrollment in the study, then every 12 weeks ]
    For participant to the expansion cohort only. DR is the time from the first documentation of objective tumor response (CR or PR) and the date of tumor progression or death due to any cause, whichever occurred first.
  • Progression Free Survival (PFS) [ Time Frame: Every 6 weeks up to 1 year from patient enrollment in the study, then every 12 weeks ]
    For participant to the expansion cohort only. Progression Free Survival (PFS) is the time from the first dose of study treatment to date of first documentation of progression (by RECIST version 1.1), death due to any cause or symptomatic deterioration (global deterioration of health status requiring discontinuation of treatment).
  • Time to Response (TTR) [ Time Frame: Every 6 weeks up to 1 year from patient enrollment in the study, then every 12 weeks ]
    For participant to the expansion cohort only. Time to Tumor Response (TTR) is the time from first dose of study treatment to the first documentation of objective tumor response (CR or PR) by RECIST version 1.1 that is subsequently confirmed.
  • Maximum plasma concentration (Cmax) of MSB0010718C [ Time Frame: 0, 1, 96 hours post-dose ]
    Cmax defined as the maximum plasma concentration of MSB0010718C
  • Maximum plasma concentration (Cmax) of AG-013736 [ Time Frame: 0, 1, 2, 3, 4, 6, 8 hours post-dose ]
    Cmax defined as the maximum plasma concentration of AG-013736
  • Time to reach the maximum plasma concentration (Tmax) of AG-013736 [ Time Frame: 0, 1, 2, 3, 4, 6, 8 hours post-dose ]
    Tmax is the time needed to reach the maximum plasma concentration of AG-013736
  • Trough plasma concentration (Ctrough) of MSB0010718C [ Time Frame: 0, 1, 96 hours post-dose ]
    Ctrough is defined as the concentration at the end of MSB0010718C dosage interval
  • AUC0-12 is the area under the curve from time 0 to 12 hours for AG-013736 [ Time Frame: 0, 1, 2, 3, 4, 6, 8 hours post-dose ]
    AUC0-12 is area under the concentration-time curve from time of dosing to 12 hours for AG-013736
  • Elimination half-life (t1/2) of AG-013736 [ Time Frame: 0, 1, 2, 3, 4, 6, 8 hours post-dose ]
    T1/2 is defined as the time required for the concentration of AG-013736 to reach half of its original value
  • Tumor tissue biomarkers [ Time Frame: baseline ]
    Tumor tissue biomarkers, including, but not limited to, PD L1 expression, tumor infiltrating CD8+ T lymphocytes, and T cell receptor gene sequence quantitation.
  • Anti-Drug Antibody (ADA) levels of MSB0010718C/Neutralizing antibodies titers for MSB0010718C [ Time Frame: Every 2 weeks up to week 7, every 4 weeks up to week 15, then Q12W ]
    Immunogenicity assessment of MSB0010718C
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)
Official Title  ICMJE A PHASE 1B, OPEN-LABEL, DOSE-FINDING STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AXITINIB (AG-013736) IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED RENAL CELL CANCER
Brief Summary This is a Phase 1b, open-label, multi-center, multiple-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D) of avelumab (MSB0010718C) in combination with axitinib (AG-013736). Once the MTD of avelumab administered in combination with axitinib is estimated (dose finding portion), the dose expansion phase will be opened to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarker modulation.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Renal Cell Cancer
Intervention  ICMJE
  • Drug: Avelumab (MSB0010718C)
    Avelumab with two dose levels: 10 mg/kg IV and 5 mg/kg IV every two weeks to find the maximum tolerated dose in combination with axitinib and continue treatment in a dose expansion.
  • Drug: Axitinib (AG-013736)
    Axitinib with two dose levels: 5 mg and 3 mg oral BID to find the maximum tolerated dose in combination with avelumab and continue treatment in a dose expansion.
Study Arms  ICMJE Experimental: Dose finding phase and dose expansion phase.
To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)
Interventions:
  • Drug: Avelumab (MSB0010718C)
  • Drug: Axitinib (AG-013736)
Publications * Choueiri TK, Larkin J, Oya M, Thistlethwaite F, Martignoni M, Nathan P, Powles T, McDermott D, Robbins PB, Chism DD, Cho D, Atkins MB, Gordon MS, Gupta S, Uemura H, Tomita Y, Compagnoni A, Fowst C, di Pietro A, Rini BI. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol. 2018 Apr;19(4):451-460. doi: 10.1016/S1470-2045(18)30107-4. Epub 2018 Mar 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 7, 2015)
55
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 22, 2020
Actual Primary Completion Date April 3, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced RCC with clear cell component
  • Primary tumor resected
  • Availability of a recent 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 enrollment AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and enrollment onto the current study. If an FFPE tissue block cannot be provided as per documented regulations,, 15 unstained slides (10 minimum) will be acceptable.
  • Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided, 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.
  • Age ≥18 years (≥ 20 years in Japan).
  • 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 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 as well as any prior therapies with other VEGF pathway inhibitors.
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis.
  • Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02493751
Other Study ID Numbers  ICMJE B9991002
2015-001137-25 ( EudraCT Number )
Javelin Renal 100 ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date December 2018

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