A Dose Finding Study To Evaluate Safety, Drug Interaction, Tumor Markers Of Axitinib In Combination With MK-3475 In Adult Patients With Previously Untreated Advanced Renal Cell Cancer
A PHASE 1B, OPEN LABEL, DOSE FINDING STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AXITINIB (AG-013736) IN COMBINATION WITH PEMBROLIZUMAB (MK-3475) IN PATIENTS WITH ADVANCED RENAL CELL CANCER
2 other identifiers
interventional
52
1 country
19
Brief Summary
Despite substantial improvements of patients outcome in advanced RCC, durable and complete response is uncommon. The majority of patients eventually develop resistance and exhibit disease progression. Combining a PD-1 inhibitor, which has shown single-agent efficacy with axitinib may provide additional clinical benefit compared to axitinib alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2014
Longer than P75 for phase_1
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 6, 2014
CompletedFirst Posted
Study publicly available on registry
May 8, 2014
CompletedStudy Start
First participant enrolled
September 16, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2017
CompletedResults Posted
Study results publicly available
June 21, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
July 3, 2019
CompletedJuly 28, 2021
July 1, 2021
2.5 years
May 6, 2014
March 28, 2018
July 26, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With Dose-Limiting Toxicities (DLT): Dose Finding Phase
DLT was defined as any of the following adverse events (AEs) occurring in the first two cycles of treatment which were attributable to one or both the study drugs: 1) Grade 4 neutropenia, 2) Febrile neutropenia lasting greater than (\>) 1 hour, 3) Grade greater than or equal to (\>=) 3 neutropenia with infection, 4) Grade \>=3 thrombocytopenia with bleeding, 4) Grade 4 thrombocytopenia, 5) Any grade \>=3 non-hematologic: non-laboratory toxicities despite maximum supportive therapy or hypertension despite maximal medical therapy, 6) Grade \>=3 non-hematologic toxicities resulted in hospitalisation or medical intervention 7) Inability to complete at least 75 percent (%) of axitinib dosing or 2 infusions of pembrolizumab within the DLT observation period (up to 42 days) due to treatment related toxicity. Severity of AEs was graded according to NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Cycle 1 Day 1 to Cycle 2 Day 21 (up to 42 days)
Secondary Outcomes (23)
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Baseline up to 28 days after last dose of study drug (approximately up to 1552 days)
Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Baseline up to 28 days after last dose of study drug (approximately up to 1552 days)
Number of Participants With Adverse Events (AEs) According to Severity of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03
Baseline up to 28 days after last dose of study drug (approximately up to 1552 days)
Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology
Baseline up to a maximum of 1083 days
Number of Participants With Laboratory Test Abnormalities: Urinalysis
Baseline up to a maximum of 1083 days
- +18 more secondary outcomes
Study Arms (1)
Dose finding phase and dose expansion phase
EXPERIMENTALTo test the maximum tolerated dose of MK-3475 at 2 mg/kg every three weeks intravenous infusion in combination with approved axitinib dose
Interventions
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype with primary tumor resected
- At least one measureable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
- Eastern Cooperative Oncology Group performance status 0 or 1
- Controlled hypertension
You may not qualify if:
- Prior treatment with systemic therapy for advanced RCC
- Prior adjuvant or neoadjuvant therapy if disease progression or relapse has occurred during or within 12 months after the last dose of treatment
- Prior treatment with any agent specifically targeting T-cell co-stimulation or checkpoint pathways
- Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis
- Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of randomization except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low grade prostate cancer with no plans for treatment intervention
- In past 12 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
- In past 6 months: deep vein thrombosis or pulmonary embolism
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (19)
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
H. Lee Moffitt Cancer Center & Research Institute, Inc.
Tampa, Florida, 33612, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Attn. Alicia Sammarco, RPh, NYU Investigational Pharmacy
New York, New York, 10016, United States
NYU Langone Medical Center
New York, New York, 10016, United States
NYU Langone
New York, New York, 10016, United States
Investigational Drug Services
Columbus, Ohio, 43210, United States
James Cancer Hospital
Columbus, Ohio, 43210, United States
The Ohio State University Brain and Spine Hospital
Columbus, Ohio, 43210, United States
Martha Morehouse Medical Plaza
Columbus, Ohio, 43221, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Henry-Joyce Cancer Clinic
Nashville, Tennessee, 37232, United States
Vanderbilt Oncology Pharmacy
Nashville, Tennessee, 37232, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
Related Publications (3)
Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, Vaishampayan U, George S, Tarazi JC, Duggan W, Perini R, Thakur M, Fernandez KC, Choueiri TK. Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial. Eur J Cancer. 2021 Mar;145:1-10. doi: 10.1016/j.ejca.2020.12.009. Epub 2021 Jan 4.
PMID: 33412465DERIVEDMartini JF, Plimack ER, Choueiri TK, McDermott DF, Puzanov I, Fishman MN, Cho DC, Vaishampayan U, Rosbrook B, Fernandez KC, Tarazi JC, George S, Atkins MB. Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma. Clin Cancer Res. 2020 Nov 1;26(21):5598-5608. doi: 10.1158/1078-0432.CCR-20-1408. Epub 2020 Aug 18.
PMID: 32816890DERIVEDAtkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, Vaishampayan U, George S, Olencki TE, Tarazi JC, Rosbrook B, Fernandez KC, Lechuga M, Choueiri TK. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 2018 Mar;19(3):405-415. doi: 10.1016/S1470-2045(18)30081-0. Epub 2018 Feb 10.
PMID: 29439857DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer, Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 6, 2014
First Posted
May 8, 2014
Study Start
September 16, 2014
Primary Completion
March 31, 2017
Study Completion
July 3, 2019
Last Updated
July 28, 2021
Results First Posted
June 21, 2019
Record last verified: 2021-07
Data Sharing
- IPD Sharing
- Will not share
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.