Studying An Investigational Drug Crizotinib (PF-02341066) In Non Non-Small Cell Lung Cancer Tumors That Are Positive For Anaplastic Lymphoma Kinase (ALK)

PHASE 1B OPEN-LABEL STUDY OF THE SAFETY AND CLINICAL ACTIVITY OF CRIZOTINIB (PF-02341066) IN TUMORS WITH GENETIC EVENTS INVOLVING THE ANAPLASTIC LYMPHOMA KINASE (ALK ) GENE LOCUS

This is a Phase 1 trial evaluating the safety and efficacy of crizotinib in patients with tumors except non-small cell lung cancer that are positive for ALK.

Study Overview

• Status: Terminated
• Conditions: Neoplasms Malignant
• Intervention / Treatment: Drug: Crizotinib

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Chaoyang District
    • Beijing, Chaoyang District, China, 100021
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
• Italy
  • Monza, Italy, 20090
    • Centro di Ricerca di Fase 1 ASST-Monza
  • Monza, Italy, 20900
    • PO San Gerardo, ASST Monza-U.O Ematologia
• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Russian Federation
  • Saint-Petersburg, Russian Federation, 197022
    • GBOU VPO "First Saint-Petersburg State Medical University n.a.I.P Pavlov" Ministry of Health
  • Saint-Petersburg, Russian Federation, 197101
    • Institute of Pedriatric Oncology, Hematology and Transplantation n.a R.M Gorbacheva
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital, Department of Internal Medicine
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group
    • Springdale, Arkansas, United States, 72762
      • Highland Oncology Group
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
    • Portland, Oregon, United States, 97239
      • OHSU Center for Health and Healing 2
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System, Institute for Translational Oncology Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• histologically or cytologically proven diagnosis of malignancy other than NSCLC
• positive for translocation or inversion event involving the ALK gene locus
• positive for ALK amplification events
• positive for ALK activating point mutations

Exclusion Criteria:

• mutations of amplifications involving the c-Met gene but not the ALK gene
• concurrent treatment on another therapeutic clinical trial
• prior therapy specifically directed against ALK

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crizotinib	Drug: Crizotinib; Crizotinib tablets, 250 mg BID, will be administered orally on a continuous dosing schedule; Other Names: PF-02341066

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious AE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care activity of daily living (ADL); Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.	From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)
Number of Participants With All-Causality TEAEs in the Pediatric Population	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious AE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication.Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.	From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)
Number of Participants With Treatment-Related TEAEs	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.	From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)
Number of Participants With Treatment-Related TEAEs in the Pediatric Population	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.	From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)
Number of Participants With Laboratory Test Results Shifted From Grade <=2 At Baseline to Grade 3 or 4 Postbaseline (Hematology and Chemistries)	Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Both hematology and clinical chemistry parameters were analyzed. Grades of severity were defined by CTCAE v4.0. Grade 1 = mild adverse event; Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated.	From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)
Number of Participants With Laboratory Test Results Shifted From Grade <=2 At Baseline to Grade 3 or 4 Postbaseline (Hematology and Chemistries) in the Pediatric Population	Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Both hematology and chemistry laboratory assessments were analyzed. Grades of severity were defined by CTCAE v4.0. Grade 1 = mild adverse event; Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Unplanned laboratory test results were also included.	From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)
Objective Response Rate (ORR) - Percentage of Participants With Objective Response	Percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) as determined by the investigators. CR = disappearance of all target lesions. PR = greater than equal to (>=) 30% decrease in sum of target lesions taking as reference baseline sum diameters. ORR based on Cheson criteria was defined similarly however, confirmation of response was not required. If participant had tumor response assessed only by RECIST or Cheson, then ORR was based on the single result. If tumor response was assessed by both RECIST and Cheson, then ORR was reported based on tumor response by Cheson criteria unless the Cheson has indeterminate result, in which case the RECIST result was reported. Participant(s) who did not have tumor assessment results from either RECIST 1.1 or Cheson criteria reported at baseline were to be excluded from the analysis.	From the date of first dose of study medication to the date of the first documentation of objective tumor progression or death on treatment due to any cause, whichever occured first (maximum 374 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) Based on Investigator Assessement	PFS was defined as the time from the date of first dose of study medication to the date of the first documentation of objective tumor progression (at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study [this includes the baseline sum if that is the smallest on study]). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered a sign of progression) or death on treatment due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. The median PFS was estimated using Kaplan-Meier method.	From the date of first dose of study medication to the date of the first documentation of objective tumor progression or death on treatment due to any cause, whichever occurs first (maximum 444 weeks)
Duration of Response (DR) Based on Investigator Assessement	DR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. CR: disappearance of all lesions; any pathological lymph nodes (target lesions [TLs]) or non-target lesions (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; PR: >=30% decrease in sum of diameter of all TLs, taking as reference baseline sum of diameters; DR (in weeks) was calculated as (first date of PD or death - first date of CR or PR +1)/7. The median DR was estimated using Kaplan-Meier estimates.	From the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum 374 weeks)
Percentage of Participants Surviving at 6 Months and 1 Year	The probability of survival at 6 months and 1 year, respectively, after the date of the first dose based on the Kaplan-Meier estimate.	At 6 months and 1 year after first dose
Overall Survival (OS)	OS is defined as the time from the date of first dose of study medication to the date of death due to any cause. OS (in months) was calculated as (date of death - date of first dose +1)/30.42. For participants still alive at the time of the analysis, for those who were lost to follow-up, and those who withdrew consent for additional follow up, the OS was censored on the last date that participants were known to be alive. Participants lacking data beyond the first dose had their OS censored at the date of first dose. The median OS was estimated using Kaplan-Meier method.	From the first dose of study treatment to the date of death due to any cause (maximum 444 weeks)
Steady-State Pre-dose Concentration (Ctrough) for Crizotinib on Day 1 of Cycles 2, 3 and 5	Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection.	Predose within 1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5
Steady-State Ctrough for PF-06260182 on Day 1 of Cycles 2, 3 and 5	Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection.	Predose within 1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5
Ctrough Ratios of PF-06260182 to Crizotinib on Day 1 of Cycles 2, 3 and 5	Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection. The ratio is calculated as: (PF-06260182 concentration/464.33)/(Crizotinib concentration/450.34), where 464.33 is molecular weight for PF-06260182 and 450.33 is molecular weight for Crizotinib.	Predose within -1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5
Number of Participants With ALK Genetic Events	Number of participants with ALK translocation/fusion, amplification, mutation and overexpression at baseline assessed by technologies including fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC), quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), ALK Fusion partners assessed by FISH or PCR; ALK gene amplification assessed by FISH or array Comparative Genomic Hybridization (aCGH), ALK Mutation assessed by PCR or direct sequencing were reported.	From Screening 28 Days Prior to Dosing Up to End of Treatment/Withdrawal (Maximum Up to Approximately 11 Years)
Phosphorylation Status of ALK in the Tumor Samples From Surgery or Biopsy Pre and Post Treatment	Tumor sample was planned to be provided to the designated central laboratory for retrospective confirmation of ALK phosphorylation status by a Pfizer designated central laboratory. The molecular profiling results were planned to include ALK fusion/translocation, mutations, amplification and overexpression.	From Screening 28 Days Prior to Dosing Up to End of Treatment/Withdrawal (Maximum Up to Approximately 11 Years)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2011
• Primary Completion (Actual): September 7, 2023
• Study Completion (Actual): September 7, 2023

Study Registration Dates

• First Submitted: May 10, 2010
• First Submitted That Met QC Criteria: May 10, 2010
• First Posted (Estimated): May 12, 2010

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: lymphoma; anaplastic lymphoma kinase; neuroblastoma; ALK; Crizotinib; neoplasm malignant
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms; Lymphoma; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: A8081013; 2010-022978-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No