Erlotinib Therapy and Subsequent Development of Mechanisms of Secondary Resistance in Patients With NSCLC
Phase: Phase 2
Diagnosis: Lung Cancer
NCT ID: NCT00997334
(View complete trial on ClinicalTrials.gov)
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.
Beth-Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital
Lecia Sequist, MD,
Massachusetts General Hospital
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
- 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
- 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.
- 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
- Pregnant or breastfeeding. Women of child-bearing potential must agree to use
adequate contraception prior to study entry and for the duration of study