Erlotinib Therapy and Subsequent Development of Mechanisms of Secondary Resistance in Patients With NSCLC
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Erlotinib
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: erlotinib; EGFR mutation; NSCLC

Summary:

      Erlotinib is a drug which targets non small cell lung cancer with a genetic change (mutation)
      in the epidermal growth factor receptor (EGFR). This drug has been used in other cancer
      research studies and information from those studies suggests that Erlotinib can control the
      growth of these cancer cells.
    

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 (the oncogene from
             the Kirsten rat sarcoma virus) 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.

          -  Incomplete healing from previous surgery

          -  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.