Proteomic Profiling in Predicting Response in Patients Receiving Erlotinib for Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

A Feasibility Study Investigating Translational Science in Chemotherapy-Naive Patients With Stage IIIb or IV Non-Small Cell Lung Cancer (NSCLC) Treated With the EGFR-TKI, Erlotinib

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00550537
• Other study ID #: VICC-THO-0640
• Secondary ID: P30CA068485VU-VI
• Status: Active, not recruiting
• Phase: Phase 2
• First received: October 26, 2007
• Last updated: July 20, 2011
• Start date: October 2007

Study information

• Verified date: July 2011
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Vanderbilt University
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Studying samples of tumor tissue, blood, and urine in the laboratory from patients receiving erlotinib may help doctors predict how patients will respond to treatment.

PURPOSE: The phase II trial is studying proteomic profiling to see how well it predicts response in patients receiving erlotinib for stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Description:

OBJECTIVES:

Primary

• To define a pre-treatment tumor proteomic profile that predicts response, stable disease, or progressive disease in patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer treated with erlotinib hydrochloride.

Secondary

• To test and refine a pre-treatment serum proteomic expression pattern that predicts response to erlotinib hydrochloride and/or carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride.

• To test and refine tumor proteomic profiles that predict response to carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride.

• To analyze individual and pattern(s) of erlotinib hydrochloride-induced genomic and proteomic biomarker changes in relation to response or non-response to treatment.

• To correlate the efficacy and toxicity of erlotinib hydrochloride with expression of EGFR, EGFR pathway, ErbB family, and other related biomarkers.

• To determine a set of biomarkers to be evaluated in tumor tissue or surrogate tissues prior to treatment with erlotinib hydrochloride to enable patient selection for therapy.

• To estimate response rate and progression-free and overall survival of patients treated with erlotinib hydrochloride as initial therapy.

• To characterize the safety profile of erlotinib hydrochloride in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily until disease progression.

At the time of disease progression, patients receive standard chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Patients with non-squamous cell non-small cell lung cancer also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses.

Tumor tissue, plasma, serum, and urine samples are collected at baseline for proteomics analysis.

After the completion of study treatment, patients are followed every 8 weeks.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 125
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following criteria:

• Stage IIIB (with pleural effusion) or stage IV disease

• Recurrent disease after prior surgery

• Measurable or evaluable disease is desirable but not required

• No untreated symptomatic brain metastases

• Patients who are neurologically unstable despite radiotherapy for the brain metastases are not eligible

• No requirement for steroids to control neurological symptoms

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• ANC = 1,500/mm³

• Hemoglobin = 9 g/dL

• Platelet count = 100,000/mm³

• Creatinine = 2.0 mg/dL

• Total bilirubin = 1.5 mg/dL

• Normal hemostasis by history

• PT/PTT within 0.5 seconds of normal range

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Willing to undergo biopsy procedures

• No known severe hypersensitivity to erlotinib hydrochloride or any of the excipients of this product

• No other concurrent malignancies or malignancies diagnosed within the past 5 years, except basal cell carcinoma or cervical cancer in situ

• No significant cardiac disease, including any of the following:

• NYHA class III or IV heart disease

• Uncontrolled dysrhythmia

• Myocardial infarction within the past 6 months

• No evidence of clinically active interstitial lung disease

• Chronic stable radiographic changes that are asymptomatic allowed

• No evidence of any other severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)

• No evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial

• No uncontrolled hypertension

• Blood pressure must be = 150/90 mmHg on a stable antihypertensive regimen

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 6 months since prior adjuvant chemotherapy

• No unresolved chronic toxicity > CTC grade 2 from prior anticancer therapy (except alopecia)

• More than 30 days since prior non-approved or investigational drugs

• No prior chemotherapy for advanced NSCLC

• No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or St. John's wort

• No concurrent administration of other drugs known to inhibit EGFR

• No other concurrent anti-neoplastic or anti-tumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy

• No other concurrent investigational agents

• Concurrent cardioprotective doses of aspirin, as recommended by the physician, for cardiovascular disease allowed

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• bevacizumab
15 mg/m2 given through a vein for every 3 weeks
• carboplatin
AUC = 6 given through a vein on day 1 of each cycle.
• erlotinib hydrochloride
150 mg taken by mouth daily
• paclitaxel
200 mg/m2 given through a vein on day 1 of each cycle.

Genetic:
• gene expression analysis
Blood and tissue collection.
• protein expression analysis
Blood and tissue collection.
• proteomic profiling
Blood and tissue collection.

Other:
• laboratory biomarker analysis
Blood and tissue collection.

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center - Cool Springs	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center at Franklin	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pre-treatment tumor proteomic profile as a predictor of response, stable disease, or progressive disease		End of treatment date	No
Secondary	Pre-treatment serum proteomic expression pattern as a predictor of response to erlotinib hydrochloride and/or carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride		End of treatment date	No
Secondary	Tumor proteomic profiles as predictors of response to carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride		End of treatment date	No
Secondary	Analysis of individual and pattern(s) of erlotinib hydrochloride-induced genomic and proteomic biomarker changes in relation to response or non-response to treatment	End of treatment date	End of treatment date	No
Secondary	Correlation of the efficacy and toxicity of erlotinib hydrochloride with expression of EGFR, EGFR pathway, ErbB family, and other related biomarkers		End of treatment date	Yes
Secondary	Determination of a set of biomarkers to be evaluated in tumor tissue or surrogate tissues prior to treatment with erlotinib hydrochloride to enable patient selection for therapy		End of treatment date	No
Secondary	Response rate		End of treatment date	No
Secondary	Progression-free and overall survival		Off study date	No
Secondary	Safety profile		30 days after completing treatment	Yes