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Trial record 1 of 1 for:    b9991002
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A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT02493751
First received: July 7, 2015
Last updated: May 22, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Renal Cell Cancer
Drug: Avelumab (MSB0010718C)
Drug: Axitinib (AG-013736)
Phase 1

Study Type: Interventional
Study Design: Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]
    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.


Estimated Enrollment: 55
Actual Study Start Date: October 2015
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose finding phase and dose expansion phase.
To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02493751

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

Locations
United States, Arizona
Oncology Research Associates, PLLC d/b/a Pinnacle Oncology Hematology Active, not recruiting
Scottsdale, Arizona, United States, 85258
United States, District of Columbia
Georgetown University Medical Center Active, not recruiting
Washington, D.C., District of Columbia, United States, 20007
United States, Massachusetts
Brigham & Women's Hospital Active, not recruiting
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center Active, not recruiting
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute Active, not recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Drug Shipment address: Attn. Alicia Sammarco, RPh,NYU Investigational Pharmacy Active, not recruiting
New York, New York, United States, 10016
Laura & Isaac Perlmutter Cancer Center At NYU Langone Active, not recruiting
New York, New York, United States, 10016
NYU Langone Medical Center Active, not recruiting
New York, New York, United States, 10016
United States, Ohio
Cleveland Clinic Active, not recruiting
Cleveland, Ohio, United States, 44195
United States, Tennessee
Henry Joyce Cancer Clinic Active, not recruiting
Nashville, Tennessee, United States, 37232-5310
Vanderbilt University Oncology Pharmacy (ship drug only) Active, not recruiting
Nashville, Tennessee, United States, 37232
United States, Utah
University of Utah, Huntsman Cancer Hospital Active, not recruiting
Salt Lake City, Utah, United States, 84112
University of Utah, Huntsman Cancer Institute Active, not recruiting
Salt Lake City, Utah, United States, 84112
Japan
Niigata University Medical & Dental Hospital Active, not recruiting
Chuo-ku, Niigata, Niigata, Japan, 951-8520
Kinki University Hospital Active, not recruiting
Osakasayama, Osaka, Japan, 589-8511
Keio University Hospital Active, not recruiting
Shinjuku-ku, Tokyo, Japan, 160-8582
United Kingdom
Mount Vernon Cancer Center, East and North Herts. NHS Trust Recruiting
London, Middlesex, United Kingdom, HA6 2RN
St Helier Hospital Recruiting
Carshalton, Surrey, United Kingdom, SM5 1AA
St. Bartholomew's Hospital Recruiting
London, United Kingdom, EC1A 7BE
The Royal Marsden NHS Foundation Trust Recruiting
London, United Kingdom, SW3 6JJ
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
The Royal Marsden NHS Foundation Trust Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02493751     History of Changes
Other Study ID Numbers: B9991002
2015-001137-25 ( EudraCT Number )
Javelin Renal 100 ( Other Identifier: Alias Study Number )
Study First Received: July 7, 2015
Last Updated: May 22, 2017

Keywords provided by Pfizer:
Cancer, renal cell cancer, kidney disease, kidney neoplasms, axitinib

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 24, 2017