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Erlotinib Is Being Studied With Or Without An Investigational Drug, PF-02341066, In Patients With Lung Cancer

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ClinicalTrials.gov Identifier: NCT00965731
Recruitment Status : Completed
First Posted : August 26, 2009
Results First Posted : January 14, 2013
Last Update Posted : October 28, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE August 24, 2009
First Posted Date  ICMJE August 26, 2009
Results First Submitted Date  ICMJE December 7, 2012
Results First Posted Date  ICMJE January 14, 2013
Last Update Posted Date October 28, 2015
Study Start Date  ICMJE January 2010
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
  • Number of Participants With Dose-Limiting Toxicities (DLT) (Phase 1) [ Time Frame: Baseline up to Day 28 ]
    Phase 1, first cycle DLT includes Grade (Gr) ≥4 hematologic possible drug-related toxicities and Gr ≥3 possible drug-related febrile neutropenia. Gr ≥3 non-hematological possible drug-related toxicities (except asymptomatic lab value elevation). Gr 3/4 nausea, vomiting or diarrhea. Gr 3 hypertension considered DLT if event unmanageable by approved pharmacologic agents or symptomatic sequelae despite medical intervention. Diagnosis of interstitial lung disease. Inability to deliver at least 80 percent (%) of planned dose during cycle 1 due to possible drug-related adverse events (AEs).
  • Progression-Free Survival (Phase 2) [ Time Frame: Baseline, every 42 days up to 20 months, disease progression, or unacceptable toxicity ]
    Time in weeks from phase 2 study randomization to first documentation of objective disease progression or death due to any cause. Progression-Free Survival was calculated as (first event date minus randomization date plus 1) divided by 7.02. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from AE data (where the outcome was "Death"; date of death reported in notice of death was used).
Original Primary Outcome Measures  ICMJE
 (submitted: August 24, 2009)
  • Phase 1 - determine the maximum tolerated dose and recommended Phase 2 dose for PF-03241066 in combination with erlotinib [ Time Frame: 12 mo ]
  • Phase 2 - Progression Free Survival (PFS) of single agent erlotinib vs Progression Free Survival (PFS) of erlotinib plus PF-02341066 [ Time Frame: 18 mo ]
Change History Complete list of historical versions of study NCT00965731 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
  • PF-02341066 (Crizotinib) Area Under the Concentration-Time Curve During Dosing Interval (AUCtau) (Phase 1) [ Time Frame: Cycle 1 (C1) Day 1 (D1) i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib ]
    AUCtau is a measure of the plasma exposure to PF-02341066. In this study, it is used to characterize PF-02341066 exposure after a single dose (Cycle 1 Day 1) and multiple doses (Cycle1 Day 15) of PF-02341066 were administered in combination of Erlotinib.
  • PF-02341066 (Crizotinib) Maximum Observed Plasma Concentration (Cmax) (Phase 1) [ Time Frame: C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib ]
    Cmax is a measure of the plasma exposure to PF-02341066. In this study, it is used to characterize PF-02341066 exposure after a single dose (Cycle 1 Day 1) and multiple doses (Cycle 1 Day 15) of PF-02341066 were administered in combination of Erlotinib
  • PF-02341066 (Crizotinib) Apparent Oral Clearance (CL/F) (Phase 1) [ Time Frame: C1D15 i.e., 15 days of giving crizotinib and erlotinib ]
    Apparent oral Clearance is a measure of combination of the rate at which a drug is removed from the blood (CL) and the bioavailability (F) after oral dose. In this study, It is used to characterize PF-02341066 CL/F after multiple doses (Cycle 1 Day 15) of PF-02341066 were administered in combination of Erlotinib.
  • PF-06260182 Area Under the Concentration-Time Curve During Dosing Interval (AUCtau) (Phase 1) [ Time Frame: C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib ]
    AUCtau is a measure of the plasma exposure to PF-06260182, a PF-02341066 metabolite. In this study, it is used to characterize the metabolite exposure after a single dose (Cycle 1 Day 1) and multiple doses (Cycle 1 Day 15) of PF-02341066 were administered in combination of Erlotinib.
  • PF-06260182 Maximum Observed Plasma Concentration (Cmax) (Phase 1) [ Time Frame: C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib ]
    Cmax is a measure of the plasma exposure to PF-06260182, a PF-02341066 metabolite. In this study, it is used to characterize the metabolite exposure after a single dose (Cycle 1 Day 1) and multiple doses (Cycle 1 Day 15) of PF-02341066 were administered in combination of Erlotinib.
  • Molecular Weight Adjusted PF-06260182-to-PF-02341006 Ratio of AUCtau (Phase 1) [ Time Frame: C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib ]
    Molecular weight adjusted PF-06260182-to-PF-02341006 ratio of AUCtau is a measure of how much PF-02341066 (parent drug) was converted to the metabolite PF-06260182 after PF-02341066 dosing. In this study, it is used to characterize the metabolite-to-parent ratio exposure after a single dose (Cycle 1 Day 1) and multiple doses (Cycle 1 Day 15) of PF-02341066 were administered in combination of Erlotinib.
  • Erlotinib Area Under the Concentration-Time Curve During Dosing Interval (AUCtau) (Phase 1) [ Time Frame: C1D-1 i.e., 1 day prior to initiation of continuous dosing of crizotinib; C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib ]
    AUCtau is a measure of the plasma exposure to erlotinib. In this study, it is used to characterize erlotinib exposure after multiple doses of erlotinib were administered alone (Day -1) and in combination of PF-02341066 (Cycle 1 Day 1 and Day 15).
  • Erlotinib Maximum Observed Plasma Concentration (Cmax) (Phase 1) [ Time Frame: C1D-1 i.e., 1 day prior to initiation of continuous dosing of crizotinib; C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib ]
    Cmax is a measure of the plasma exposure to erlotinib. In this study, it is used to characterize erlotinib exposure after multiple doses of erlotinib were administered alone (Day -1) and in combination of PF-02341066 (Cycle 1 Day 1 and Day 15).
  • Erlotinib Apparent Oral Clearance (CL/F) (Phase 1) [ Time Frame: C1D15 i.e., 15 days of giving crizotinib and erlotinib ]
    Apparent oral Clearance is a measure of combination of the rate at which a drug is removed from the blood (CL) and the bioavailability (F) after oral dose. In this study, it is used to characterize erlotinib CL/F after multiple doses in combination with PF-02341066 (Cycle 1 Day 15).
  • Ratio of Adjusted Means of Erlotinib AUCtau (Crizotinib + Erlotinib / Erlotinib Alone) (Phase 1) [ Time Frame: C1D-1 (i.e., 1 day prior to initiation of continuous dosing of crizotinib) to C1D15 (i.e., 15 days of giving crizotinib and erlotinib) ]
    Ratio of adjusted means of Erlotinib AUCtau (Crizotinib + Erlotinib / Erlotinib Alone) is a measure of the plasma exposure to erlotinib after erlotinib dosing with crizotinib compared with that after erlotinib dosing alone. In this study, it is used to characterize the effect magnitude of crizotinib on the erlotinib exposure after combinational use of crizotinib and erlotinib.
  • Ratio of Adjusted Means of Erlotinib Cmax (Crizotinib + Erlotinib / Erlotinib Alone) (Phase 1) [ Time Frame: C1D-1 (i.e., 1 day prior to initiation of continuous dosing of crizotinib) to C1D15 (i.e., 15 days of giving crizotinib and erlotinib) ]
    Ratio of adjusted means of Erlotinib Cmax (Crizotinib + Erlotinib / Erlotinib Alone) is a measure of the plasma exposure to erlotinib after erlotinib dosing with crizotinib compared with that after erlotinib dosing alone. In this study, it is used to characterize the effect magnitude of crizotinib on the erlotinib exposure after combinational use of crizotinib and erlotinib.
  • Progression-Free Survival (Phase 1) [ Time Frame: Baseline, every 42 days until disease progression or unacceptable toxicity ]
    Time in weeks from phase 1 randomization to first documentation of objective disease progression or death due to any cause. Progression-Free Survival was calculated as (first event date minus randomization date plus 1) divided by 7.02. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD), or from AE data (where the outcome was "Death"; date of death reported in notice of death was used).
  • Duration of Response (Phase 1) [ Time Frame: Baseline, every 42 days until disease progression or unacceptable toxicity ]
    Median duration (50 percent [%]) of tumor response. Duration of response (DR) defined as time from start of first documented objective tumor response [Complete Response (CR) or Partial Response (PR)] to first documented objective tumor progression or death due to any cause, whichever occurs first. DR calculated as (Weeks) = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.02. CR: disappearance of a target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.
  • Percentage of Participants With Objective Response (Phase 1) [ Time Frame: Baseline, every 42 days until disease progression or unacceptable toxicity ]
    Percentage of participants during phase 1 with objective response based assessment of confirmed CR or confirmed PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Confirmed responses: persist on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of nontarget disease. No new lesions.
  • Plasma Level of Soluble Marker: c-Met Ectodomain (Phase 1) [ Time Frame: Baseline and Day 50 (Cycle 3, Day 1) ]
    Levels of soluble protein biomarker c-MET was analyzed at Baseline and at Day 50.
  • Plasma Level of Soluble Marker: Hepatocyte Growth Factor (HGF) Scatter Factor (Phase 1) [ Time Frame: Baseline and Day 50 (Cycle 3, Day 1) ]
  • Plasma Level of Soluble Marker: c-Met Ectodomain (Phase 2) [ Time Frame: Baseline and Day 50 (Cycle 3, Day 1) ]
  • Plasma Level of Soluble Marker: HGF Scatter Factor (Phase 2) [ Time Frame: Baseline and Day 50 (Cycle 3, Day 1) ]
  • Duration of Response (Phase 2) [ Time Frame: Baseline, every 42 days up to 20 months, disease progression, or unacceptable toxicity ]
    Median duration (50%) of tumor response. DR defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurs first. DR calculated as (Weeks) = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.02. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of nontarget disease. No new lesions.
  • Percentage of Participants With Confirmed CR, PR or Stable Disease (SD) at Phase 2 [ Time Frame: Week 6 and Week 12 ]
    Percentage of participants during phase 2 with confirmed CR, confirmed PR or SD according to RECIST 1.1. Also known as Disease Control Rate (DCR). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of nontarget disease. No new lesions. SD: neither sufficient shrinkage or increase to qualify for PR or PD.
  • Percentage of Participants With Objective Response (Phase 2) [ Time Frame: Baseline, every 42 days up to 20 months, disease progression, or unacceptable toxicity ]
    Percentage of participants during phase 2 with objective response based assessment of confirmed CR or confirmed PR according to RECIST (1.1). Confirmed responses: persist on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of nontarget disease. No new lesions.
  • Overall Survival (OS) at Phase 2 [ Time Frame: Baseline until death, up to 20 months ]
    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.
  • European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire (QLQ-C30) Score at Phase 2 [ Time Frame: Baseline and every 21 days, up to 20 months ]
    Phase 2 EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, 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=better level of functioning or greater degree of symptoms.
  • EORTC Quality of Life Questionnaire -Lung Cancer 13 (QLQ-LC13) Score at Phase 2 [ Time Frame: Baseline and every 21 days, up to 20 months ]
    QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
  • Plasma Concentration of PF-02341066 and Erlotinib (Phase 2) [ Time Frame: Day 1 of cycles 1, 3, and 5 (i.e., up to 15 weeks) at 0 (pre-dose) and 2 to 6 hours post dose ]
    Plasma concentration of PF-02341066 and erlotinib when administered in combination during phase 2
  • Plasma Concentration of Erlotinib (Phase 2) [ Time Frame: Day 1 of cycles 1, 3, and 5 (i.e., up to 15 weeks) at 0 hours (pre-dose) ]
    Plasma concentration of erlotinib when administered as a single agent during phase 2
  • Percentage of Participants With Mutations in Tumor Tissue (Phase 2) [ Time Frame: Screening ]
    Tumor tissue samples collected for molecular profiling were to be analyzed to assess Kirsten rat sarcoma (KRAS) mutations, mutations, amplification and expression of Epidermal Growth Factor Receptor (EGFR) and c-Met, and echinoderm microtubule-associated protein-like 4-anaplastic large cell receptor kinase (EML4-ALK) fusion in tumors.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2009)
  • Phase 1 - Pharmacokinetic parameters of PF-02341066 and erlotinib [ Time Frame: 12 mo ]
  • Phase 2 - Duration of Response (DR), disease control rate at 6 and 12 weeks, Objective Rate Response (ORR) and Overall Survival (OS) (erlotinib vs erlotinib plus PF-02341066) [ Time Frame: 18 mo ]
Current Other Pre-specified Outcome Measures
 (submitted: July 14, 2015)
  • Maximum Tolerated Dose (MTD) of PF-02341066 When Administered in Combination With Erlotinib (Phase 1) [ Time Frame: Baseline up to 28 days (Cycle 1) ]
    MTD: the combination dose level of PF-02341066 and erlotinib in which 0/6 or 1/6 participants experienced DLT after 28 days of treatment (Cycle 1) with the next higher dose level having at least 2/3 or 2/6 participants with DLT during Cycle 1 of treatment.
  • Recommended Phase 2 Dose (RP2D) of PF-02341066 When Administered in Combination With Erlotinib (Phase 1) [ Time Frame: Baseline up to 28 days (Cycle 1) ]
    If no more than 1/6 participants presented with a DLT during Cycle 1 at the MTD, then this dose level was considered the RP2D. If >1/6 participants experienced a DLT, then the previous lower level was considered the MTD and RP2D.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Erlotinib Is Being Studied With Or Without An Investigational Drug, PF-02341066, In Patients With Lung Cancer
Official Title  ICMJE Phase 1/2, Open Label, Randomized Study Of The Safety, Efficacy, And Pharmacokinetics Of Erlotinib With Or Without Pf 02341066 In Patients With Advanced Non Small Cell Adenocarcinoma Of The Lung.
Brief Summary This is a Phase 1/2 study comparing the safety and anti-tumor activity of erlotinib alone versus erlotinib in combination with PF-02341066 in patients with advanced non-small cell lung cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Erlotinib
    Erlotinib, 150 mg, QD will be administered orally on a continuous schedule (Phase 2 only)
  • Drug: Erlotinib
    For Phase 1 - escalating doses of erlotinib will be administered orally on a continuous schedule. The planned doses to be evaluated are 100 and 150 mg QD. The dose determined in Phase 1 will be used in Phase 2
  • Drug: PF-02341066
    For Phase 1 - escalating doses of PF-02341066 will be administered orally on a continuous schedule. The planned doses to be evaluated are 200 and 250 mg BID. The dose determined in Phase 1 will be used in Phase 2
Study Arms  ICMJE
  • Active Comparator: Erlotinib
    Intervention: Drug: Erlotinib
  • Experimental: Erlotinib + PF-02341066
    Interventions:
    • Drug: Erlotinib
    • Drug: PF-02341066
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 7, 2012)
27
Original Estimated Enrollment  ICMJE
 (submitted: August 24, 2009)
175
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • histologically proven diagnosis of Non-Small Cell Lung Cancer (NSCLC) that is locally advanced or metastatic and of the adenocarcinoma subtype (including mixed adenosquamous histology)
  • evident disease progression by Response Evaluation Criterion in Solid Tumors (RECIST) after at least one but no more than 2 chemotherapy regimens for advanced disease
  • tumors must have measurable disease as per RECIST

Exclusion Criteria:

  • known interstitial lung disease
  • prior treatment with an agent that is known or proposed to be active by action on EGFR tyrosine kinase or c-Met/HGF (Phase 2 Portion)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00965731
Other Study ID Numbers  ICMJE A8081002
2009-012377-35 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP