NCT00932893 · CITED IN SOURCE DOCUMENTS

An Investigational Drug, PF-02341066 Is Being Studied Versus Standard Of Care In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

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

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2017-01-02

This is a Phase 3 trial comparing the safety and anti-tumor activity of PF-02341066 versus pemetrexed or docetaxel in patients with advanced non-small cell lung cancer with specific gene profile involving the ALK gene after failure of one previous chemotherapy regimen that included one platinum drug.

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

Progression-Free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Overall Survival Probability at Months 6 and 12

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outcome · POSTED

Percentage of Participants With Objective Response (OR)

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outcome · POSTED

Percentage of Participants With Disease Control at Week 6

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outcome · POSTED

Percentage of Participants With Disease Control at Week 12

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outcome · POSTED

Duration of Response (DR)

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outcome · POSTED

Time to Tumor Response (TTR)

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outcome · POSTED

Plasma Concentration of Crizotinib

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outcome · POSTED

Number of Participants With Categorical Maximum QTcF for Crizotinib

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outcome · POSTED

Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins

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outcome · POSTED

Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough

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outcome · POSTED

European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

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outcome · POSTED

European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)

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outcome · POSTED

European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)

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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 non-small cell lung cancer * positive for the ALK fusion gene (test provided by a central laboratory) * must have had disease progression after only one prior chemotherapy and that regimen but must have included one platinum drug * tumors must be measurable Exclusion Criteria: * prior treatment with PF-02341066 * current treatment in another clinical trial
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: PF-02341066
label
PF-02341066
type
EXPERIMENTAL
description
Investigator selection of either pemetrexed or docetaxel as the active comparator
intervention Names
Drug: Pemetrexed
Drug: Docetaxel
label
Pemetrexed or Docetaxel
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
PF-02341066
description
PF-02341066, 250 mg BID will be administered orally on a continuous schedule
name
PF-02341066
type
DRUG
arm Group Labels
Pemetrexed or Docetaxel
description
Pemetrexed, 500 mg/m\^2, will be administered by i.v. infusion over 10 minutes on Day 1 of each 21-day cycle
name
Pemetrexed
type
DRUG
arm Group Labels
Pemetrexed or Docetaxel
description
Docetaxel, 75 mg/m\^2, will be administered by i.v. infusion over 1 hour on Day 1 of each 21-day cycle
name
Docetaxel
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 347
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
PFS: Time in months from randomization to first documentation of objective disease progression as determined by independent radiology review or to death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria version 1.1 (RECIST v1.1), as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
measure
Progression-Free Survival (PFS)
time Frame
Randomization until progressive disease (PD) or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)

secondary Outcomes

description
OS: Time in months from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 30.4.
measure
Overall Survival (OS)
time Frame
Randomization until death (up to 4.5 years)
description
Overall survival probability at Month 6 and 12 was defined as the probability of survival at 6 and 12 months respectively, after the randomization of study treatment. The survival probability was estimated using the Kaplan-Meier method.
measure
Overall Survival Probability at Months 6 and 12
time Frame
Month 6, 12
description
Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 millimeter \[mm\] short axis). PR: at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Objective response is based on independent radiology review.
measure
Percentage of Participants With Objective Response (OR)
time Frame
Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)
description
Disease control: participants with CR, PR, or stable disease (SD) according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis). PR: at least 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Disease control is based on independent radiology review.
measure
Percentage of Participants With Disease Control at Week 6
time Frame
Week 6
description
Disease control: participants with CR, PR, or SD according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis). PR: at least 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
measure
Percentage of Participants With Disease Control at Week 12
time Frame
Week 12
description
Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7.02. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
measure
Duration of Response (DR)
time Frame
Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)
description
Time from date of randomization to first documentation of objective tumor response. TTR was calculated for the subgroup of participants with objective tumor response. Objective tumor response was defined as CR or PR according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis). PR: at least 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
measure
Time to Tumor Response (TTR)
time Frame
Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)
description
Only participants receiving crizotinib were to be analyzed for this outcome measure as per planned analysis.
measure
Plasma Concentration of Crizotinib
time Frame
Pre-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of Cycles 2, 3, 5
description
QT interval corrected using Fridericia's formula (QTcF): QT interval (time corresponding to the beginning of depolarization to re-polarization of the ventricles) divided by cube root of RR interval. Maximum QTcF was categorized as less than (\<) 450 milliseconds (msec), 450 msec to \<480 msec, 480 msec to \<500 msec, and more than or equal to (\>=) 500 msec. A participant is reported only once under the maximum QTcF interval observed at any of the time-points. Only participants receiving crizotinib were to be analyzed for this outcome measure as per planned analysis.
measure
Number of Participants With Categorical Maximum QTcF for Crizotinib
time Frame
Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 1, 2
description
Descriptive statistics (absolute value and change from baseline as measured by ratio to baseline) for each best overall response category (CR, PR, SD, PD or combined) have been used to summarize the data from optional soluble c-Met ectodomain assays for crizotinib treated patients.
measure
Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins
time Frame
Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 2, end of treatment (up to 112 weeks)
description
TTD in pain (pain in chest from European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer \[EORTC QLQ-LC13\]), dyspnea (from EORTC QLQ-LC13), or cough (from EORTC QLQ-LC13) symptoms was defined as the time from randomization to the earliest time the participant's score showed a 10 point or higher increase from baseline in any of the three symptoms from the instrument. The transformed score of pain, dyspnea, and cough symptom scales of EORTC QLQ-LC13 range from 0 to 100, greater scores = higher symptom severity.
measure
Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough
time Frame
Baseline up to end of treatment (up to 112 weeks)
description
EORTC QLQ-C30: included global health status/quality of life (QoL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score for Global Qol/functional scales=better level of QoL/functioning or higher score for symptom scale=greater degree of symptoms.
measure
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
time Frame
Baseline, Day (D) 1 of each cycle (C) until disease progression, end of treatment (EOT, up to 112 weeks)

Full study description

brief Summary: This is a Phase 3 trial comparing the safety and anti-tumor activity of PF-02341066 versus pemetrexed or docetaxel in patients with advanced non-small cell lung cancer with specific gene profile involving the ALK gene after failure of one previous chemotherapy regimen that included one platinum drug.

Source references

references

citation
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pmid
30822515
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