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

NCT ID: NCT02493751

Last Updated: 2022-02-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-26

Study Completion Date

2021-03-04

Brief Summary

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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

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Conditions

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Renal Cell Cancer

Study Design

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Allocation Method

NA

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose finding phase and dose expansion phase.

To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)

Group Type EXPERIMENTAL

Avelumab (MSB0010718C)

Intervention Type DRUG

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.

Axitinib (AG-013736)

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Scottsdale Healthcare Hospitals d/b/a HonorHealth

Scottsdale, Arizona, United States

Site Status

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Laura & Isaac Perlmutter Cancer Center At NYU Langone

New York, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Henry Joyce Cancer Clinic

Nashville, Tennessee, United States

Site Status

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Site Status

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Niigata University Medical & Dental Hospital

Chuo-ku, Niigata, Niigata, Japan

Site Status

Kindai University Hospital

Sayama, Osaka, Japan

Site Status

Keio University Hospital

Shinjuku-ku, Tokyo, Japan

Site Status

Mount Vernon Cancer Center, East and North Herts. NHS Trust

London, Middlesex, United Kingdom

Site Status

St Helier Hospital

Carshalton, Surrey, United Kingdom

Site Status

St. Bartholomew's Hospital

London, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Site Status

Countries

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United States Japan United Kingdom

References

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Rini BI, Atkins MB, Choueiri TK, Teresi RE, Rosbrook B, Thakur M, Hutson TE. Plain language summary looking at how long side effects last after treatment with axitinib is stopped in people with advanced renal cell carcinoma. Future Oncol. 2023 Dec;19(40):2623-2629. doi: 10.2217/fon-2023-0233. Epub 2023 Aug 1.

Reference Type DERIVED
PMID: 37526095 (View on PubMed)

Larkin J, Oya M, Martignoni M, Thistlethwaite F, Nathan P, Ornstein MC, Powles T, Beckermann KE, Balar AV, McDermott D, Gupta S, Philips GK, Gordon MS, Uemura H, Tomita Y, Wang J, Michelon E, di Pietro A, Choueiri TK. Avelumab Plus Axitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: Long-Term Results from the JAVELIN Renal 100 Phase Ib Trial. Oncologist. 2023 Apr 6;28(4):333-340. doi: 10.1093/oncolo/oyac243.

Reference Type DERIVED
PMID: 36576173 (View on PubMed)

Masters JC, Khandelwal A, di Pietro A, Dai H, Brar S. Model-informed drug development supporting the approval of the avelumab flat-dose regimen in patients with advanced renal cell carcinoma. CPT Pharmacometrics Syst Pharmacol. 2022 Apr;11(4):458-468. doi: 10.1002/psp4.12771. Epub 2022 Feb 27.

Reference Type DERIVED
PMID: 35166465 (View on PubMed)

Rini BI, Atkins MB, Choueiri TK, Thomaidou D, Rosbrook B, Thakur M, Hutson TE. Time to Resolution of Axitinib-Related Adverse Events After Treatment Interruption in Patients With Advanced Renal Cell Carcinoma. Clin Genitourin Cancer. 2021 Oct;19(5):e306-e312. doi: 10.1016/j.clgc.2021.03.019. Epub 2021 Apr 5.

Reference Type DERIVED
PMID: 33947608 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29530667 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-001137-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Javelin Renal 100

Identifier Type: OTHER

Identifier Source: secondary_id

B9991002

Identifier Type: -

Identifier Source: org_study_id

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