Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatment erlotinib
Phase phase 2
Target EGFR
Sponsor David M. Jackman, MD
Collaborator Beth Israel Deaconess Medical Center
Start date December 2009
End date January 2015
Trial size 60 participants
Trial identifier NCT00997334, 09-210

Summary

The purpose of this research study is to assess the frequency of the development of mutations (especially EGFR mutations) that lead to resistance to erlotinib in people with non-small cell lung cancer (NSCLC). The investigators will also be looking to see if the participant's NSCLC improves with erlotinib and why it may eventually stop responding to erlotinib.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive standard dose erlotinib, with blood draws for correlative science every 2 cycles.
erlotinib Tarceva
Taken orally once daily

Primary Outcomes

Measure
To prospectively assess the frequency of different genetic mechanisms of secondary resistance in patients' tumors during treatment with erlotinib.
time frame: 2 years

Secondary Outcomes

Measure
To measure the steady-state plasma concentrations of erlotinib during the course of patients' treatment.
time frame: 3 years
To analyze from both free plasma DNA and DNA from circulating tumor cells of erlotinib-treated patients for the orginal sensitizing EGFR mutations and genetic changes associated with secondary resistance.
time frame: 3 years
To measure clinical outcomes in patients with known sensitizing mutations in their tumor EGFR when treated with first-line erlotinib.
time frame: 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically confirmed non-small cell lung cancer, stage IV or IIIB with a malignant pleural or pericardial effusion. Patients with stage I or II non-small cell lung cancer who have undergone surgical resection but who subsequently relapse with metastatic disease or a malignant pleural effusion are also eligible. - Documentation of a sensitizing mutation of the epidermal growth factor receptor. In addition, there must be a sufficient tissue for analysis of KRAS mutations and MET amplification. - At least one measurable or evaluable site of disease as defined by revised RECIST (version 1.1) criteria. - 18 years of age or older - No more than one prior systemic therapy regimen for advanced non-small cell lung cancer. Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC will not count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen. - 3 or more weeks since prior major surgery - 2 or more weeks since prior radiation - ECOG performance status 0-1 - Life expectancy > 8 weeks - Adequate hematologic, renal, and hepatic function - Willingness to undergo repeat tumor biopsy at the time of disease progression. Exclusion Criteria: - Untreated and/or uncontrolled central nervous system metastases. Patients with prior brain metastases must have had definitive treatment (radiation or surgery) and must be clinically stable off steroids for at least 1 week prior to enrollment. - More than one prior systemic chemotherapy for advanced non-small cell lung cancer. , Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC willnot count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen. - Prior exposure to erlotinib or other treatments targeting the HER family axis. - Active malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. - Any process that compromises the ability to swallow and/or absorb oral medication. - A history of any of the following autoimmune skin disorders: Sjogren's syndrome, scleroderma, dermatomyositis, and systemic lupus erythematosus. - Significant medical history or unstable medical conditions. - Concurrent use of warfarin. Patients must be off warfarin for at least one week prior to initiation of erlotinib. Other non-warfarin anticoagulants are permitted. - Patients who require ongoing concomitant use of one of the strong inhibitors/inducers of CYP3A4. - Pregnant or breastfeeding. Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.

Additional Information

Official title First-Line Erlotinib Therapy and the Subsequent Development of Mechanisms of Secondary Resistance in Patients With Non-Small Cell Lung Cancer and Known Sensitizing EGFR Mutations
Principal investigator David Jackman, MD
Description - Participants will take erlotinib orally once a day. Each treatment cycle lasts 28 days. - While on the study, participants will be required to be seen in the clinic on Day 1 of each treatment cycle. During these visit, the following tests and procedures will be done: physical exam and blood tests. They will also return for blood work during Cyle 1 Day 8. - At the end of every two cycles an assessment of the participant's tumor will be done by CT and/or MRI (this is part of regular cancer care) as well as the following: Urine test and blood tests. - At the end of study treatment the following procedures will be done: blood tests, assessment of the tumor by CT and/or MRI and a new biopsy of the tumor or removal of fluid containing tumor cells.
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by Dana-Farber Cancer Institute.