A Study Of Crizotinib Versus Chemotherapy In Previously Untreated ALK Positive East Asian Non-Small Cell Lung Cancer Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01639001
First received: July 10, 2012
Last updated: July 4, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
NSCLC (Non-small Cell Lung Cancer)
Drug: Crizotinib
Drug: Pemetrexed/Cisplatin
Drug: Pemetrexed/Carboplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Health Related Quality of Life (HRQoL) [ Time Frame: Cycle 1 day 1 to end of treatment or withdrawal or crossover. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Survival Probabilities [ Time Frame: At 1 year and at 18 months, after the date of randomization. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: September 2012
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Crizotinib
Crizotinib
Drug: Crizotinib
250 mg two times daily [BID], oral, on a continuous daily dosing schedule. Cycles are defined in 21 day periods.
Active Comparator: Chemotherapy
Chemotherapy [Option at Investigator's Choice]
Drug: 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.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01639001

  Show 40 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01639001     History of Changes
Other Study ID Numbers: A8081029
Study First Received: July 10, 2012
Last Updated: July 4, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Crizotinib
ALK positive
ALK
Anaplastic Lymphoma Kinase
NSCLC
Non-Small Cell Lung Cancer
Frontline
1L
Previously Untreated
East Asian
Non-Squamous

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Cisplatin
Crizotinib
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2015