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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00965731
First received: August 24, 2009
Last updated: July 14, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Erlotinib
Drug: PF-02341066
Phase 1

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 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.

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Dose-Limiting Toxicities (DLT) (Phase 1) [ Time Frame: Baseline up to Day 28 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • Plasma Level of Soluble Marker: c-Met Ectodomain (Phase 2) [ Time Frame: Baseline and Day 50 (Cycle 3, Day 1) ] [ Designated as safety issue: No ]
  • Plasma Level of Soluble Marker: HGF Scatter Factor (Phase 2) [ Time Frame: Baseline and Day 50 (Cycle 3, Day 1) ] [ Designated as safety issue: No ]
  • Duration of Response (Phase 2) [ Time Frame: Baseline, every 42 days up to 20 months, disease progression, or unacceptable toxicity ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Maximum Tolerated Dose (MTD) of PF-02341066 When Administered in Combination With Erlotinib (Phase 1) [ Time Frame: Baseline up to 28 days (Cycle 1) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 27
Study Start Date: January 2010
Study Completion Date: January 2014
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Erlotinib Drug: Erlotinib
Erlotinib, 150 mg, QD will be administered orally on a continuous schedule (Phase 2 only)
Experimental: Erlotinib + PF-02341066 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  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: NCT00965731

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California, Irving - Medical Center
Orange, California, United States, 92868-3298
University of California, Irvine Medical Center Pharmacy
Orange, California, United States, 92868-3298
University of California Irvin
Orange, California, United States, 92868
United States, Florida
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
United States, Missouri
Siteman Cancer Center -West County
Creve Coeur, Missouri, United States, 63141
Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110-1094
Washington University, School of Medicine
St. Louis, Missouri, United States, 63110
Siteman Cancer Center
St. Peters, Missouri, United States, 63376
United States, Ohio
James Care in Kenny
Columbus, Ohio, United States, 43221
OSU East
Columbus, Ohio, United States, 43205
The Ohio State University James Cancer Hospital
Columbus, Ohio, United States, 43210
United States, Texas
Cancer Therapy & Research Center @ UTHSCSA
San Antonio, Texas, United States, 78229
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
University of Washington Medical Center
Seattle, Washington, United States, 98195
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: NCT00965731     History of Changes
Other Study ID Numbers: A8081002, 2009-012377-35
Study First Received: August 24, 2009
Results First Received: December 7, 2012
Last Updated: July 14, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Lung Neoplasms
Crizotinib

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Crizotinib
Erlotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 03, 2015