A Phase II Single-Arm Trial Assessing the Use of an Ex Vivo Sensitivity Assay to Predict Response of Relapsed Metastatic Non-Small Cell Lung Cancer Patients to Erlotinib
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Lung Cancer
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Quantitative assessment of phospho-ERK
- Status
- Completed
- Last Updated
- 15 years ago
Overview
Brief Summary
RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors learn how well patients will respond to treatment.
PURPOSE: This phase II trial is studying how well a laboratory test predicts response to erlotinib in patients with metastatic or unresectable non-small cell lung cancer that did not respond to previous treatment.
Detailed Description
OBJECTIVES: Primary * Determine whether the extent of inhibition of ERK phosphorylation in lung cancer cells exposed ex vivo and in vivo to erlotinib hydrochloride significantly differs between responding and nonresponding patients with relapsed, metastatic or unresectable non-small cell lung cancer. Secondary * Determine whether the extent of inhibition of epidermal growth factor receptor (EGFR) and AKT phosphorylation in lung cancer cells exposed ex vivo and in vivo to erlotinib hydrochloride significantly differs between these 2 groups of patients. * Correlate the extent of inhibition of EGFR, ERK, and AKT phosphorylation in lung cancer cells exposed ex vivo with erlotinib hydrochloride with in vivo objective tumor response to erlotinib hydrochloride in these patients. * Correlate EGFR gene mutation and amplification status with pharmacodynamic evidence of response to erlotinib hydrochloride in these patients. OUTLINE: This is an open-label, pilot study. Patients receive oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor fine-needle aspiration biopsies under ultrasound or CT scan guidance at baseline and between days 12-15 for laboratory studies. Laboratory studies include quantitative western blot and enzyme-linked immunosorbent assays, gene mutation and amplification, and ex vivo assays. Tumor cells are also analyzed for changes in phosphorylation status and/or expression levels of pharmacodynamic markers, including total- and phospho-epidermal growth factor receptor, total- and phospho-ERK, and total- and phospho-AKT. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Quantitative assessment of phospho-ERK
Extent of inhibition of ERK phosphorylation by erlotinib hydrochloride
Clinical response
Secondary Outcomes
- Extent of inhibition of epidermal growth factor receptor (EGFR) and AKT phosphorylation by erlotinib hydrochloride
- Toxicity
- Frequency and proportion of patients with complete response, partial response, stable disease, and progressive disease
- Comparison of ex vivo and in vivo effects of erlotinib hydrochloride
- Proportion of patients with EGFR gene amplification and gene mutation with an ex vivo response and clinical response