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: March 6, 2014
Last verified: March 2014
  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
Phase 2

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) [ 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:
  • Area Under the Concentration-Time Curve (AUC) [ Time Frame: Days 1 and 15 of Cycle 1 at 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours post dose ] [ Designated as safety issue: No ]
    Phase 1 AUC is a measure of the serum concentration of PF-02341066 in combination treatment with erlotinib over time. It is used to characterize drug absorption.

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Days 1 and 15 of Cycle 1 at 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours post dose ] [ Designated as safety issue: No ]
    Phase 1 Cmax of PF-02341066 in combination treatment with erlotinib

  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: Days 1 and 15 of Cycle 1 at 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours post dose ] [ Designated as safety issue: No ]
    Phase 1 Cmin of PF-02341066 in combination treatment with erlotinib

  • Apparent Oral Clearance (CL/F) [ Time Frame: Days 1 and 15 of Cycle 1 at 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours post dose ] [ Designated as safety issue: No ]
    Phase 1 clearance of PF-02341066 is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Plasma Decay Half-Life (t1/2) [ Time Frame: Days 1 and 15 of Cycle 1 at 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours post dose ] [ Designated as safety issue: No ]
    Phase 1 plasma decay half-life is the time measured for the plasma concentration of PF-02341066 to decrease by one half.

  • Area Under the Concentration-Time Curve (AUC) (Phase 1) [ Time Frame: Days -1, 1, and 15 of Cycle 1 at 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours post dose ] [ Designated as safety issue: No ]
    Phase 1 AUC is a measure of the serum concentration of erlotinib alone and in combination treatment with PF-02341066 over time. It is used to characterize drug absorption.

  • 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 all 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: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target 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 ]
  • 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: 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: 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: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.

  • Percentage of Participants With Confirmed CR, PR or Stable Disease (SD) [ 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: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target 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: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.

  • Overall Survival (OS) [ 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 [ Time Frame: Baseline and every 21 days ] [ 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 [ Time Frame: Baseline and every 21 days ] [ 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 [ Time Frame: Day 1 of Cycles 1, 3, and 5 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 [ Time Frame: Day 1 of Cycles 1, 3, and 5 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 [ 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 [ 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 [ Time Frame: Baseline up to 28 days (Cycle 1) ] [ Designated as safety issue: No ]
    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
Pfizer Investigational Site
Birmingham, Alabama, United States, 35294
Pfizer Investigational Site
Birmingham, Alabama, United States, 35233
United States, California
Pfizer Investigational Site
Orange, California, United States, 92868-3298
United States, Florida
Pfizer Investigational Site
Fort Lauderdale, Florida, United States, 33308
United States, Missouri
Pfizer Investigational Site
Creve Coeur, Missouri, United States, 63141
Pfizer Investigational Site
St. Louis, Missouri, United States, 63110-1094
Pfizer Investigational Site
St. Louis, Missouri, United States, 63110
Pfizer Investigational Site
St. Peters, Missouri, United States, 63376
United States, Ohio
Pfizer Investigational Site
Columbus, Ohio, United States, 43205
Pfizer Investigational Site
Columbus, Ohio, United States, 43221
Pfizer Investigational Site
Columbus, Ohio, United States, 43210
United States, Texas
Pfizer Investigational Site
San Antonio, Texas, United States, 78229
United States, Washington
Pfizer Investigational Site
Seattle, Washington, United States, 98195
Pfizer Investigational Site
Seattle, Washington, United States, 98109
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
Study First Received: August 24, 2009
Results First Received: December 7, 2012
Last Updated: March 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Lung Neoplasms
Crizotinib

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

ClinicalTrials.gov processed this record on July 24, 2014