Study Evaluating the Safety Of HKI-272 (Neratinib) In Subjects With Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to learn whether HKI-272 is safe and effective in treating non-small cell lung cancer.

Official Title
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A Phase 2 Study of HKI-272 In Subjects With Advanced Non-Small Cell Lung Cancer

Conditions
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Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

Intervention / Treatment
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* Drug: HKI-272


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic diagnosis of NSCLC and current stage IIIB (with pleural effusion) or IV, not curable with conventional therapy. For Arm C, less than or equal to 20 pack-years smoking history and current non smoker. A pack year = number of packs of cigarettes smoked per day x years smoked. Progression following at least 12 weeks of treatment with Tarceva or Iressa. (Arms A and B only) ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2 (not declining within past 2 weeks). Tumor sample available and adequate for analysis. At least one measurable target lesion. Adequate cardiac, kidney, and liver function Adequate blood counts Exclusion Criteria: More than 3 prior cytotoxic chemotherapy treatments for relapsed or metastatic disease. Significant cardiac disease or dysfunction. Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2. Active central nervous system metastases, as indicated by clinical symptoms and/or progressive growth. Use of Tarceva or Iressa within 14 days of treatment day 1 (Arms A and B only). Major surgery, chemotherapy, radiotherapy, investigational drugs, or other cancer therapy within 3 weeks of treatment day 1. Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom. Inability or unwillingness to swallow HKI-272 capsules. Pregnant or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prior Tarceva or Iressa With EGFR Mutation<br>HKI-272 administered to patients whose disease has progressed following > or = 12 weeks of treatment with Tarceva or Iressa and who have a tumor with an EGFR mutation demonstrated at screening | Drug: HKI-272<br>* 320mg or 240mg daily by mouth. The starting dose was reduced from 320mg to 240mg per amendment #1 to the protocol for subject safety and tolerability.<br>* Other names: Neratinib;|
| Experimental: Prior Tarceva or Iressa w/o EGFR Mutation<br>HKI-272 administered to patients whose disease has progressed following > or = 12 weeks of treatment with Tarceva or Iressa and who have a tumor without an EGFR mutation demonstrated at screening | Drug: HKI-272<br>* 320mg or 240mg daily by mouth. The starting dose was reduced from 320mg to 240mg per amendment #1 to the protocol for subject safety and tolerability.<br>* Other names: Neratinib;|
| Experimental: No Prior EGFR Tyrosine Kinase Inhibitor Treatment<br>HKI-272 administered to patients with no prior EGFR tyrosine kinase inhibitor treatment, adenocarcinoma, < or = 20 pack-year smoking history, and current non-smoker (no requirement for EGFR mutation) | Drug: HKI-272<br>* 320mg or 240mg daily by mouth. The starting dose was reduced from 320mg to 240mg per amendment #1 to the protocol for subject safety and tolerability.<br>* Other names: Neratinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate for Neratinib in Patients With Non-small Cell Lung Cancer | Objective response rate as reported by Independent Assessment (radiographic review by independent radiologists) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions. | From first dose date to progression/death or last tumor assessment, up to three years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate for Neratinib in Patients With Non-small Cell Lung Cancer | Clinical benefit rate is the percentage of patients with Partial or Complete Response, or with Stable Disease >= 12 Weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | From first dose date to progression/death or last tumor assessment, up to three years. | 
| Duration of Response for Neratinib in Patients With Non-small Cell Lung Cancer | Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, PD, or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions. | From start date of response to first PD, assessed up to three years after the first randomization. | 
| Progression Free Survival for Neratinib in Patients With Non-small Cell Lung Cancer | Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v 1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From first dose date to progression/death, assessed up to three years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, HKI-272, Neratinib, Nerlynx