Overview

This trial is active, not recruiting.

Condition nsclc (non-small cell lung cancer)
Treatments crizotinib, pemetrexed/cisplatin, pemetrexed/carboplatin
Phase phase 3
Targets ALK, c-MET, ROS1
Sponsor Pfizer
Start date September 2012
End date June 2015
Trial size 207 participants
Trial identifier NCT01639001, A8081029

Summary

This is a Phase III, Randomized, Open-label, Efficacy and Safety Study of Crizotinib single agent versus Chemotherapy Regimens (Pemetrexed/Cisplatin or Pemetrexed/Carboplatin) in First-Line ALK (Anaplastic Lymphoma Kinase) Positive East Asian Non-Small Cell Lung Cancer Patients. The objective of the study is to demonstrate that Crizotinib is superior to first-line chemotherapy pemetrexed/cisplatin or pemetrexed/carboplatin in prolonging Progression Free Survival (PFS) in East Asian patients with advanced Non-Squamous NSCLC whose tumors harbor a translocation or inversion event involving the ALK (Anaplastic Lymphoma Kinase) gene locus.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Crizotinib
crizotinib
250 mg two times daily [BID], oral, on a continuous daily dosing schedule. Cycles are defined in 21 day periods.
(Active Comparator)
Chemotherapy [Option at Investigator's Choice]
pemetrexed/cisplatin
Option 1: Pemetrexed/Cisplatin; Pemetrexed, 500 mg/m^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Cisplatin, 75 mg/m^2 will be administered by infusion after adequate hydration according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and cisplatin will be repeated every 3 weeks for a maximum of 6 cycles.
pemetrexed/carboplatin
Option 2: Pemetrexed/Carboplatin. Pemetrexed, 500 mg/m^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Carboplatin, at a dose calculated to produce an AUC of 5 or 6 mg.min/mL will be administered by infusion according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and carboplatin will be repeated every 3 weeks for a maximum of 6 cycles.

Primary Outcomes

Measure
Progression-Free Survival (PFS) based on Response Evaluation Criterion in Solid Tumors [RECIST] version 1.1 (documented by independent radiology laboratory)
time frame: From randomization to date of first documentation of objective tumor progression or death due to any cause, whichever occurs first. Follow-up will continue for 18 months after last patient is randomized or until required number of PFS events is observed.

Secondary Outcomes

Measure
Objective Response Rate (ORR) (confirmed by independent radiology review)
time frame: From randomization to complete response (CR) or partial response (PR). Up to 18 months follow-up or until required number of PFS events is observed.
Duration of Response (DR)
time frame: From first documentation of objective tumor response (CR or PR) to first documentation of objective tumor progression or to death. Up to 18 months follow-up or until required number of PFS events is observed.
Overall Survival (OS)
time frame: From randomization to the date of death due to any cause. Follow-up will continue until death or 36 months after the randomization of the last patient.
Time To Deterioration (TTD)
time frame: From randomization to deterioration while on study treatment. Up to 18 months follow-up or until required number of PFS events is observed.
Health Related Quality of Life (HRQoL)
time frame: Cycle 1 day 1 to end of treatment or withdrawal or crossover.
Time To Progression (TTP)
time frame: From the date of randomization to the date of the first documentation of objective tumor progression. Up to 18 months follow-up or until required number of PFS events is observed.
Intracranial Time To Progression (IC-TTP)
time frame: From the date of randomization to the date of the first documentation of objective tumor progression but only considering intracranial disease. Up to 18 months follow-up or until required number of PFS events is observed.
Extracranial Time To Progression (EC-TTP)
time frame: From the date of randomization to the date of the first documentation of objective tumor progression but only considering extracranial disease. Up to 18 months follow-up or until required number of PFS events is observed.
Survival Probabilities
time frame: At 1 year and at 18 months, after the date of randomization.
Disease Control Rate (DCR)
time frame: At 12 weeks, after the date of randomization. Up to 18 months follow-up or until required number of PFS events is observed.
Time to Tumor Response (TTR)
time frame: From randomization to the date of the first documentation of objective tumor progression. Up to 18 months follow-up or until required number of PFS events is observed.

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

Inclusion Criteria: - Histologically or cytologically proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung. - Positive for translocation or inversion events involving the ALK gene locus. - No prior systemic treatment for locally advanced or metastatic disease. Patients with brain metastases only if treated and neurologically stable for at least 2 weeks and are not taking any medications contraindicated in Exclusion Criteria - Evidence of a personally signed and dated informed consent document and willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of patient reported outcome [PRO] measures. Exclusion Criteria: - Current treatment on another therapeutic clinical trial. - Prior therapy directly targeting ALK. - Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack. Appropriate treatment with anticoagulants is permitted. - Ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, uncontrolled atrial fibrillation of any grade, or QTc interval >470 msec. - Pregnancy or breastfeeding. - Use of drugs or foods that are known potent CYP3A inducers/inhibitors Concurrent use of drugs that are CYP3A substrates with narrow therapeutic indices. - Known HIV infection - History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior radiation pneumonitis. - Other severe acute or chronic medical conditions (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or end-stage renal disease on hemodialysis, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study.

Additional Information

Official title Phase 3, Randomized, Open-Label Study Of The Efficacy And Safety Of Crizotinib Versus Pemetrexed/Cisplatin Or Pemetrexed/Carboplatin In Previously Untreated East Asian Patients With Non-Squamous Carcinoma Of The Lung Harboring A Translocation Or Inversion Event Involving The Anaplastic Lymphoma Kinase (ALK) Gene Locus
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Pfizer.