NCT01121588 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2025-01-23

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs)

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outcome · POSTED

Number of Participants With All-Causality TEAEs in the Pediatric Population

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outcome · POSTED

Number of Participants With Treatment-Related TEAEs

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outcome · POSTED

Number of Participants With Treatment-Related TEAEs in the Pediatric Population

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outcome · POSTED

Number of Participants With Laboratory Test Results Shifted From Grade <=2 At Baseline to Grade 3 or 4 Postbaseline (Hematology and Chemistries)

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outcome · POSTED

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

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outcome · POSTED

Objective Response Rate (ORR) - Percentage of Participants With Objective Response

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outcome · POSTED

Progression-Free Survival (PFS) Based on Investigator Assessement

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outcome · POSTED

Duration of Response (DR) Based on Investigator Assessement

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outcome · POSTED

Percentage of Participants Surviving at 6 Months and 1 Year

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Steady-State Pre-dose Concentration (Ctrough) for Crizotinib on Day 1 of Cycles 2, 3 and 5

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outcome · POSTED

Steady-State Ctrough for PF-06260182 on Day 1 of Cycles 2, 3 and 5

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outcome · POSTED

Ctrough Ratios of PF-06260182 to Crizotinib on Day 1 of Cycles 2, 3 and 5

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outcome · POSTED

Number of Participants With ALK Genetic Events

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outcome · POSTED

Phosphorylation Status of ALK in the Tumor Samples From Surgery or Biopsy Pre and Post Treatment

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 15 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: Crizotinib
label
Crizotinib
type
EXPERIMENTAL

interventions

arm Group Labels
Crizotinib
description
Crizotinib tablets, 250 mg BID, will be administered orally on a continuous dosing schedule
name
Crizotinib
other Names
PF-02341066
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 44
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs)
time Frame
From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)
description
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.
measure
Number of Participants With All-Causality TEAEs in the Pediatric Population
time Frame
From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)
description
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.
measure
Number of Participants With Treatment-Related TEAEs
time Frame
From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)
description
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.
measure
Number of Participants With Treatment-Related TEAEs in the Pediatric Population
time Frame
From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)
description
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.
measure
Number of Participants With Laboratory Test Results Shifted From Grade <=2 At Baseline to Grade 3 or 4 Postbaseline (Hematology and Chemistries)
time Frame
From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)
description
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.
measure
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
time Frame
From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)
description
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.
measure
Objective Response Rate (ORR) - Percentage of Participants With Objective Response
time Frame
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 Outcomes

description
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.
measure
Progression-Free Survival (PFS) Based on Investigator Assessement
time Frame
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)
description
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.
measure
Duration of Response (DR) Based on Investigator Assessement
time Frame
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)
description
The probability of survival at 6 months and 1 year, respectively, after the date of the first dose based on the Kaplan-Meier estimate.
measure
Percentage of Participants Surviving at 6 Months and 1 Year
time Frame
At 6 months and 1 year after first dose
description
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.
measure
Overall Survival (OS)
time Frame
From the first dose of study treatment to the date of death due to any cause (maximum 444 weeks)
description
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.
measure
Steady-State Pre-dose Concentration (Ctrough) for Crizotinib on Day 1 of Cycles 2, 3 and 5
time Frame
Predose within 1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5
description
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.
measure
Steady-State Ctrough for PF-06260182 on Day 1 of Cycles 2, 3 and 5
time Frame
Predose within 1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5
description
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.
measure
Ctrough Ratios of PF-06260182 to Crizotinib on Day 1 of Cycles 2, 3 and 5
time Frame
Predose within -1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5
description
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.
measure
Number of Participants With ALK Genetic Events
time Frame
From Screening 28 Days Prior to Dosing Up to End of Treatment/Withdrawal (Maximum Up to Approximately 11 Years)
description
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.
measure
Phosphorylation Status of ALK in the Tumor Samples From Surgery or Biopsy Pre and Post Treatment
time Frame
From Screening 28 Days Prior to Dosing Up to End of Treatment/Withdrawal (Maximum Up to Approximately 11 Years)

Full study description

brief Summary: 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.

Source references