Erlotinib Is Being Studied With Or Without An Investigational Drug, PF-02341066, In Patients With Lung Cancer
This study is ongoing, but not recruiting participants.
Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00965731
First received: August 24, 2009
Last updated: April 23, 2013
Last verified: April 2013
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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 |
| Estimated Study Completion Date: | October 2013 |
| 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
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: | April 23, 2013 |
| 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 May 16, 2013