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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02133742
Recruitment Status : Active, not recruiting
First Posted : May 8, 2014
Last Update Posted : March 14, 2018
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: Axitinib Drug: MK-3475 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 2014
Actual Primary Completion Date : March 2017
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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
Drug: Axitinib
Axitinib at starting dose of 5 mg and 3 mg BID.

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.

Primary Outcome Measures :
  1. Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: Baseline up to 6 weeks ]
    Baseline up to 6 weeks of the combination treatment that are considered related to study medication.

Secondary Outcome Measures :
  1. Duration of Response (DR) [ Time Frame: 18 months ]
    Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

  2. Percentage of Participants With Objective Response [ Time Frame: 18 months ]
    Percentage of participants with OR based assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed remission are those with repeat bone marrow showing less than 5 percent (%) myeloblasts with normal maturation of all cell lines and absolute values of the peripheral blood lasting at least 2 months. PR are those with all CR criteria except at least 50% decrease in the blasts over the pretreatment.

  3. Progression-Free Survival (PFS) [ Time Frame: 18 months ]
    Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (Weeks) = (first event date minus first dose date plus 1) divided by 7

  4. Overall Survival (OS) [ Time Frame: five years ]
    Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.

  5. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: up to 2.5 years ]
    Cmax, based PK parameters on Lead in Day 7 and Day 1 Cycle 7

  6. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: up to 2.5 years ]
    Summarized by dose, cycle, day and time

  7. Apparent Oral Clearance (CL/F) [ Time Frame: up to 2.5 years ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  8. Immunogenicity [ Time Frame: Up to 2.5 years ]
    anti-drug antibodies of MK-3475

  9. Eastern Cooperative Oncology Group [ECOG] performance status [ Time Frame: Up to 2.5 years ]

    ECOG-PS measured on-therapy (time between first dose and last dose date with a 30-day lag) assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction;

    1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hrs), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead.

  10. Presence (rate) or absence of blood biomarkers [ Time Frame: Up to 2.5 years ]
    To identify biomarkers (FGF, IL8, VEGF...) of complete response and relapse/progression if occurs

Information from the National Library of Medicine

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02133742

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United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute, Inc.
Tampa, Florida, United States, 33612
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Drug Shipment Address: Attn. Alicia Sammarco, RPh, NYU Investigational Pharmacy
New York, New York, United States, 10016
NYU Langone Medical Center
New York, New York, United States, 10016
NYU Langone
New York, New York, United States, 10016
United States, Ohio
Investigational Drug Services (Drug Management Only)
Columbus, Ohio, United States, 43210
James Cancer Hospital
Columbus, Ohio, United States, 43210
The James Cancer Hospital
Columbus, Ohio, United States, 43210
Martha Morehouse Medical Plaza
Columbus, Ohio, United States, 43221
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Henry-Joyce Cancer Clinic
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
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Study Director: Pfizer Call Center Pfizer

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Pfizer Identifier: NCT02133742     History of Changes
Other Study ID Numbers: A4061079
First Posted: May 8, 2014    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018

Keywords provided by Pfizer:
Axitinib and MK-3475
patients with advanced Renal Cell Cancer.

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