Proteomic Profiling in Predicting Response in Patients Receiving Erlotinib for Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
- Conditions
- Lung Cancer
- Interventions
- Genetic: gene expression analysisGenetic: protein expression analysisGenetic: proteomic profilingOther: laboratory biomarker analysis
- Registration Number
- NCT00550537
- Lead Sponsor
- Vanderbilt-Ingram Cancer Center
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 116
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment erlotinib hydrochloride Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. Treatment gene expression analysis Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. Treatment protein expression analysis Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. Treatment proteomic profiling Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. Treatment laboratory biomarker analysis Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. Treatment bevacizumab Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. Treatment carboplatin Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression. Treatment paclitaxel Erlotinib followed by paclitaxel + carboplatin (+ bevacizumab in non-squamous) at the time disease progression.
- Primary Outcome Measures
Name Time Method Pre-treatment Tumor Proteomic Profile as a Predictor of Response, Stable Disease, or Progressive Disease End of treatment date
- Secondary Outcome Measures
Name Time Method 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 Tumor Proteomic Profiles as Predictors of Response to Carboplatin and Paclitaxel After Failing Treatment With Erlotinib Hydrochloride End of treatment date 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
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 Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC Through study completion, an average of 1 year PFS is defined as the time from on erlotinib treatment date to progression or death (whichever comes first) before cross-over to PC or PC+B. For those did not progressed nor died, they were censored at the last follow up (either the off erlotinib treatment date or lost follow up date). The median survival time and 95% confidence interval were estimated using Kaplan-meier method.
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 Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC Through study completion, an average of 1 year Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), \>=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. The response rate is calculated as the percentage of PR+CR among patients assessed for response.
Number of Patients With Worst-grade Toxicities Per Grade Through study completion, an average of 1 year The intensity of the AE will be graded according to the Common Toxicity Criteria (CTC) of the (US) National Cancer Institute (NCI) - Cancer Therapy Evaluation Program (CTEP) \[version 3.0 of December 2003\] (Appendix B).
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AEOverall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC Through study completion, an average of 1 year The overall survival time is defined as the time from on treatment to death. Patients were censored of they were alive at the last follow up date. The median survival time and its confidence interval were estimated using Kaplan-meier method.
Trial Locations
- Locations (7)
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, 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 at Franklin
🇺🇸Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center - Cool Springs
🇺🇸Nashville, Tennessee, United States