Erlotinib Therapy and Subsequent Development of Mechanisms of Secondary Resistance in Patients With NSCLC
This trial is active, not recruiting.
|Condition||non-small cell lung cancer|
|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|
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.
|Endpoint classification||efficacy study|
|Intervention model||single group assignment|
Patients receive standard dose erlotinib, with blood draws for correlative science every 2 cycles.
To prospectively assess the frequency of different genetic mechanisms of secondary resistance in patients' tumors during treatment with erlotinib.
time frame: 2 years
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
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.
|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.|
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