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Crizotinib Plus Pembrolizumab In Alk-Positive Advanced Non Small Cell Lung Cancer Patients

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ClinicalTrials.gov Identifier: NCT02511184
Recruitment Status : Terminated (Decision based on the low enrollment mainly due to high efficacy drugs available in 1st line ALK-positive NSCLC (eg alectinib), not due to any safety concerns)
First Posted : July 29, 2015
Last Update Posted : March 26, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Pfizer

Brief Summary:
The purpose of this study has 2 phases, a Dose Finding Phase will determine the maximum tolerated dose . The Dose Expansion Phase will explore the safety, tolerability, and anti-tumor activity of the combination.

Condition or disease Intervention/treatment Phase
ALK-positive Advanced NSCLC Drug: Crizotinib Drug: Pembrolizumab Phase 1

Detailed Description:

The patients will be screened for up to 28 days before they start treatment to determine if they meet eligibility criteria. The screening procedures will include physical examination, blood work and radiological scans.

In the dose finding phase, patients who meet eligibility criteria will receive crizotinib at the dose level assigned that will be taken on daily basis and pembrolizumab 200 mg intravenous infusion every 3 weeks.

Once a Crizotinib dose level is decided, the dose expansion cohort will start enrolling patients who meet eligibility criteria.

All patients will be followed up every three weeks. Blood samples will be drawn to test for safety and tumor activities and radiological scans will be performed on certain timepoints to determine the antitumor activities.

There will be a quality of life questionnaire administered at certain time points during the study.

The study will have a quality assurance plan that addresses data validation and registry procedures. There is a plan to visit the investigator site for routine monitoring and auditing.

The team will conduct source data verification to assess the accuracy, completeness, or representativeness of registry data by comparing the data to external data sources (e.g., medical records, paper or electronic case report forms, or interactive voice response systems).

The study will also include a statistical analysis plan describing the analytical principles and statistical techniques to be employed in order to address the primary and secondary objectives of this study, as specified in the study protocol or statistical plan.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study Of Crizotinib In Combination With Pembrolizumab (Mk-3475) In Patients With Untreated Advanced Alk-translocated Non Small Cell Lung Cancer
Actual Study Start Date : October 19, 2015
Actual Primary Completion Date : December 20, 2017
Actual Study Completion Date : December 20, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose finding and dose expansion phases
Find and expand the maximum tolerated dose of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks.
Drug: Crizotinib
To test 3 dose levels of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks

Drug: Pembrolizumab
To test pembrolizumab at 200 mg every 3 weeks in combination with crizotinib at 3 dose levels.




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


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 3 years ]
    Percentage of participants with objective response (OR) based assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).

  2. Duration of Response (DR) [ Time Frame: 3 Years ]
    Time in months 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.

  3. Time to Tumor Response (TTR) [ Time Frame: 3 years ]
    The timeframe that participants reach an objective response (OR) based assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).

  4. Progression-Free Survival (PFS) [ Time Frame: 3 years ]
    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.

  5. PDL1 Expression [ Time Frame: 3 years ]
    Association between tumor PD L1 expression assessed by PD L1 and endpoints of clinical outcome

  6. Pembrolizumab Ctrough [ Time Frame: 3 years ]
    To characterize the predose concentration of pembrolizumab

  7. Crizotinib (Ctrough) [ Time Frame: 3 years ]
    The predose concentration of crizotinib

  8. Crizotinib Cmax [ Time Frame: 3 years ]
    Maximum plasma concentration

  9. Crizotinib Tmax [ Time Frame: 3 years ]
    The time to maximum plasma concentration

  10. Crizotinib AUC(0-8) [ Time Frame: 3 years ]
    area under the plasma concentration time curve from 0 to 8 hours

  11. Crizotinib AUC Tau [ Time Frame: 3 years ]
    The area under the plasma concentration time curve over the dosing interval

  12. Crizotinib CL/F [ Time Frame: 3 years ]
    The apparent plasma clearance

  13. PF--06260182 Cmax [ Time Frame: 3 years ]
    Maximum plasma concentration

  14. PF--06260182 Tmax [ Time Frame: 3 years ]
    The time to maximum plasma concentration

  15. PF--06260182 Ctrough [ Time Frame: 3 years ]
    The pre-dose concentration

  16. PF--06260182 AUC [ Time Frame: 3 years ]
    The area under the plasma concentration time curve over the dosing interval

  17. PF--06260182 MRCmax [ Time Frame: 3 years ]
    Maximum plasma concentration; metabolite to parent ratio

  18. PF--06260182 MRAUCtau [ Time Frame: 3 years ]
    The area under the plasma concentration time curve over the dosing interval; metabolite to parent ratio

  19. PF--06260182 AUCtau [ Time Frame: 3 years ]
    The area under the plasma concentration time curve over the dosing interval



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
Criteria

Inclusion Criteria:

  • Histologically or cytologically proved diagnosis of locally advanced recurrent or metastatic non-squamous NSCLC that is not suitable for local curative treatment.
  • Alk-positive NSCLC as determined by a test that is approved or validated for use as a companion diagnostic test.
  • No prior systemic therapy for metastatic disease.
  • Adjuvant chemotherapy more than 12 months prior to study enrollment.
  • Measurable disease as per RECIST 1.1
  • ECOG PS 0 or 1.

Exclusion Criteria:

  • Prior exposure to ALK receptor tyrosine kinase inhibitor, anti-PD1, anti-PDL1 or any drug targeting T-cell checkpoint pathways.
  • known diagnosis of immunodeficiency or is receiving systemic steroid therapy or other form of immunosuppressive therapy within 7 days of clinical trial treatment.
  • Active autoimmune disease that has required systemic treatment in the past 3 months.
  • History of extensive disseminated interstitial fibrosis or any grade of interstitial lung disease.

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 ClinicalTrials.gov identifier (NCT number): NCT02511184


Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham, IDS Pharmacy
Birmingham, Alabama, United States, 35249
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
UC San Diego Moores Cancer Center - Investigational Drug Services
La Jolla, California, United States, 92037-0845
UC San Diego Medical Center - La Jolla(Thornton Hospital)
La Jolla, California, United States, 92037
University Of California / San Diego Moores Cancer Center
La Jolla, California, United States, 92093
UC San Diego Medical Center - Hillcrest
San Diego, California, United States, 92103
United States, Georgia
Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308
Emory University Hospital
Atlanta, Georgia, United States, 30322
The Emory Clinic
Atlanta, Georgia, United States, 30322
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Ohio
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Washington
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Swedish Investigational Drug Services Pharmacy
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Pfizer
Merck Sharp & Dohme Corp.
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02511184     History of Changes
Other Study ID Numbers: A8081054
KEYNOTE 050 ( Other Identifier: Merck Sharp & Dohme Corp )
CRIZOTINIB ( Other Identifier: Alias Study Number )
First Posted: July 29, 2015    Key Record Dates
Last Update Posted: March 26, 2018
Last Verified: March 2018

Keywords provided by Pfizer:
crizotinib
pembrolizumab
ALK-positive NSCLC
Lung Cancer
ALK-translocated NSCLC
Non Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Crizotinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action