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

NCT ID: NCT02133742

Last Updated: 2021-07-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-16

Study Completion Date

2019-07-03

Brief Summary

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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.

Detailed Description

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Conditions

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Renal Cell Carcinoma

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 MK-3475 at 2 mg/kg every three weeks intravenous infusion in combination with approved axitinib dose

Group Type EXPERIMENTAL

Axitinib

Intervention Type DRUG

Axitinib at starting dose of 5 mg and 3 mg BID.

MK-3475

Intervention Type DRUG

MK-3475 with two dose levels: 2 mg/kg every three weeks to find the maximum tolerated dose and continue treatment in a dose expansion phase.

Interventions

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Axitinib

Axitinib at starting dose of 5 mg and 3 mg BID.

Intervention Type DRUG

MK-3475

MK-3475 with two dose levels: 2 mg/kg every three weeks to find the maximum tolerated dose and continue treatment in a dose expansion phase.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

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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Georgetown University Medical Center

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

Site Status

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Tampa, Florida, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, 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

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Attn. Alicia Sammarco, RPh, NYU Investigational Pharmacy

New York, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

NYU Langone

New York, New York, United States

Site Status

Investigational Drug Services

Columbus, Ohio, United States

Site Status

James Cancer Hospital

Columbus, Ohio, United States

Site Status

The Ohio State University Brain and Spine Hospital

Columbus, Ohio, United States

Site Status

Martha Morehouse Medical Plaza

Columbus, Ohio, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

Site Status

Vanderbilt Oncology Pharmacy

Nashville, Tennessee, United States

Site Status

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 33412465 (View on PubMed)

Martini 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.

Reference Type DERIVED
PMID: 32816890 (View on PubMed)

Atkins 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.

Reference Type DERIVED
PMID: 29439857 (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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KN-035

Identifier Type: OTHER

Identifier Source: secondary_id

A4061079

Identifier Type: -

Identifier Source: org_study_id

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