Clinical trial NCT00965731: Erlotinib Is Being Studied With Or Without An Investigational Drug, PF-02341066, In Patients With Lung Cancer
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Keywords: Lung Neoplasms
Crizotinib
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-08-26
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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)

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLT) (Phase 1)
timeFrame: Baseline up to Day 28
measure: Progression-Free Survival (Phase 2)
timeFrame: Baseline, every 42 days up to 20 months, disease progression, or unacceptable toxicity
Secondary outcomes:
measure: PF-02341066 (Crizotinib) Area Under the Concentration-Time Curve During Dosing Interval (AUCtau) (Phase 1)
timeFrame: 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
measure: PF-02341066 (Crizotinib) Maximum Observed Plasma Concentration (Cmax) (Phase 1)
timeFrame: C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib
measure: PF-02341066 (Crizotinib) Apparent Oral Clearance (CL/F) (Phase 1)
timeFrame: C1D15 i.e., 15 days of giving crizotinib and erlotinib
measure: PF-06260182 Area Under the Concentration-Time Curve During Dosing Interval (AUCtau) (Phase 1)
timeFrame: C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib
measure: PF-06260182 Maximum Observed Plasma Concentration (Cmax) (Phase 1)
timeFrame: C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib
measure: Molecular Weight Adjusted PF-06260182-to-PF-02341006 Ratio of AUCtau (Phase 1)
timeFrame: C1D1 i.e., 1 day of giving crizotinib and erlotinib; and C1D15, i.e., 15 days of giving crizotinib and erlotinib
measure: Erlotinib Area Under the Concentration-Time Curve During Dosing Interval (AUCtau) (Phase 1)
timeFrame: 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
measure: Erlotinib Maximum Observed Plasma Concentration (Cmax) (Phase 1)
timeFrame: 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
measure: Erlotinib Apparent Oral Clearance (CL/F) (Phase 1)
timeFrame: C1D15 i.e., 15 days of giving crizotinib and erlotinib
measure: Ratio of Adjusted Means of Erlotinib AUCtau (Crizotinib + Erlotinib / Erlotinib Alone) (Phase 1)
timeFrame: 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)
measure: Ratio of Adjusted Means of Erlotinib Cmax (Crizotinib + Erlotinib / Erlotinib Alone) (Phase 1)
timeFrame: 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)
measure: Progression-Free Survival (Phase 1)
timeFrame: Baseline, every 42 days until disease progression or unacceptable toxicity
measure: Duration of Response (Phase 1)
timeFrame: Baseline, every 42 days until disease progression or unacceptable toxicity
measure: Percentage of Participants With Objective Response (Phase 1)
timeFrame: Baseline, every 42 days until disease progression or unacceptable toxicity
measure: Plasma Level of Soluble Marker: c-Met Ectodomain (Phase 1)
timeFrame: Baseline and Day 50 (Cycle 3, Day 1)
measure: Plasma Level of Soluble Marker: Hepatocyte Growth Factor (HGF) Scatter Factor (Phase 1)
timeFrame: Baseline and Day 50 (Cycle 3, Day 1)
measure: Plasma Level of Soluble Marker: c-Met Ectodomain (Phase 2)
timeFrame: Baseline and Day 50 (Cycle 3, Day 1)
measure: Plasma Level of Soluble Marker: HGF Scatter Factor (Phase 2)
timeFrame: Baseline and Day 50 (Cycle 3, Day 1)
measure: Duration of Response (Phase 2)
timeFrame: Baseline, every 42 days up to 20 months, disease progression, or unacceptable toxicity
measure: Percentage of Participants With Confirmed CR, PR or Stable Disease (SD) at Phase 2
timeFrame: Week 6 and Week 12
measure: Percentage of Participants With Objective Response (Phase 2)
timeFrame: Baseline, every 42 days up to 20 months, disease progression, or unacceptable toxicity
measure: Overall Survival (OS) at Phase 2
timeFrame: Baseline until death, up to 20 months
measure: European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire (QLQ-C30) Score at Phase 2
timeFrame: Baseline and every 21 days, up to 20 months
measure: EORTC Quality of Life Questionnaire -Lung Cancer 13 (QLQ-LC13) Score at Phase 2
timeFrame: Baseline and every 21 days, up to 20 months
measure: Plasma Concentration of PF-02341066 and Erlotinib (Phase 2)
timeFrame: 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
measure: Plasma Concentration of Erlotinib (Phase 2)
timeFrame: Day 1 of cycles 1, 3, and 5 (i.e., up to 15 weeks) at 0 hours (pre-dose)
measure: Percentage of Participants With Mutations in Tumor Tissue (Phase 2)
timeFrame: Screening
Other outcomes:
measure: Maximum Tolerated Dose (MTD) of PF-02341066 When Administered in Combination With Erlotinib (Phase 1)
timeFrame: Baseline up to 28 days (Cycle 1)
measure: Recommended Phase 2 Dose (RP2D) of PF-02341066 When Administered in Combination With Erlotinib (Phase 1)
timeFrame: Baseline up to 28 days (Cycle 1)
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Orange
country: United States
facility: University of California, Irvine Medical Center Pharmacy
state: California
city: Orange
country: United States
facility: University of California, Irving - Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvin
state: California
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Creve Coeur
country: United States
facility: Siteman Cancer Center -West County
state: Missouri
city: St. Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: St. Louis
country: United States
facility: Washington University, School of Medicine
state: Missouri
city: St. Peters
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Columbus
country: United States
facility: OSU East
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University James Cancer Hospital
state: Ohio
city: Columbus
country: United States
facility: James Care in Kenny
state: Ohio
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center @ UTHSCSA
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: