Erlotinib Therapy and Subsequent Development of Mechanisms of Secondary Resistance in Patients With NSCLC

Status: Recruiting
Phase: Phase 2
Diagnosis: Lung Cancer
NCT ID: NCT00997334 (View complete trial on
DFCI Protocol ID: 09-210


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.


Conducting Institutions:
Beth-Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
Lecia Sequist, MD, Massachusetts General Hospital

Site-responsible Investigators:
David Jackman, MD, Dana-Farber Cancer Institute
Daniel Costa, MD, Beth Israel Deaconess Medical Center

Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100
Dana-Farber Cancer Institute: Kelly Masone, 617-632-3383,
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060

Eligibility Criteria

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 prior systemic therapy for advanced non-small cell lung cancer (includes chemotherapy and EGFR inhibitors), though adjuvant therapy for resected NSCLC is acceptable as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. - 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. - Prior systemic chemotherapy for advanced non-small cell lung cancer, though adjuvant therapy for resected NSCLC is acceptable as long as it is completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. - 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.
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