Clinical trial NCT02511184: Crizotinib Plus Pembrolizumab In Alk-Positive Advanced Non Small Cell Lung Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: ALK-positive Advanced NSCLC
Keywords: crizotinib
pembrolizumab
ALK-positive NSCLC
Lung Cancer
ALK-translocated NSCLC
Non Small Cell Lung Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2015-07-29
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicity (DLT)
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: 2 years
measure: Objective Response Rate (ORR)
timeFrame: Baseline, Week 9 and every 6 weeks thereafter, for about 2 years
measure: Duration of Response
timeFrame: Baseline, Week 9 and every 6 weeks thereafter, for about 2 years
measure: Time to Tumor Response
timeFrame: Baseline, Week 9 and every 6 weeks thereafter, for about 2 years
measure: Progression Free Survival
timeFrame: Baseline, Week 9 and every 6 weeks thereafter, for about 2 years
measure: 6-Month, 12-Month and 18-Month Progression Free Survival Probabilities
timeFrame: Month 6, Month 12, and Month 18
measure: Overall Survival
timeFrame: Day 1 to end of study (for about 2 years)
measure: 12-Month and 18-Month Overall Survival Probabilities
timeFrame: Month 12 and Month 18
measure: Number of Participants With Maximum Grade in Laboratory Hematology Test Shifting From Grade 0, 1 or 2 at Baseline to Grade 3 or 4 During Treatment
timeFrame: 2 years
measure: Number of Participants With Maximum Grade in Laboratory Chemistry Test Shifting From Grade 0, 1 or 2 at Baseline to Grade 3 or 4 During Treatment
timeFrame: 2 years
measure: Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Time to Maximum Plasma Concentration (Tmax) of Crizotinib for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Time to Maximum Plasma Concentration (Tmax) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Apparent Plasma Clearance (CL/F) of Crizotinib for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Apparent Plasma Clearance (CL/F) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group
timeFrame: Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)
measure: Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group
timeFrame: Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)
measure: Serum Concentration of Pembrolizumab
timeFrame: Prior to and at end of pembrolizumab infusion, 120 hours and 336 hours post Day 1 dosing of Cycle 1; pre-dose on Day 1 of Cycles 2, 4,6, 8, 12 and 16; end of Day 1 dosing of Cycle 8; End of Treatment visit
measure: Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria
timeFrame: Screening
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, IDS Pharmacy
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center - Investigational Drug Services
state: California
city: La Jolla
country: United States
facility: UC San Diego Medical Center - La Jolla(Thornton Hospital)
state: California
city: La Jolla
country: United States
facility: University Of California / San Diego Moores Cancer Center
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center - Hillcrest
state: California
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Swedish Investigational Drug Services Pharmacy
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: