Study Evaluating HKI-272 (Neratinib) In Subjects With Advanced Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to learn whether neratinib is safe and effective in treating women with advanced human epidermal growth factor receptor 2 (HER2) positive breast cancer.

Detailed Description
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Arm A: HER2 gene amplification and disease progression following at least 6 weeks of standard doses of Herceptin; Arm B: HER2 gene amplification and no prior Herceptin or HER2-targeted treatment.

Official Title
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Phase 2 Study of HKI-272 In Subjects With Advanced Breast Cancer

Conditions
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Breast Neoplasms, Neoplasms

Intervention / Treatment
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* Drug: neratinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic diagnosis of breast cancer and current stage IIIB, IIIC, or IV Progression following at least 6 weeks of standard doses of Herceptin (Arm A only) Over-expression of HER2 Tumor tissue available and adequate for analysis at screening At least one measurable lesion Exclusion Criteria: Prior treatment with Herceptin (Arm B only) More than 4 prior cytotoxic chemotherapy regimens Subjects with bone or skin as the only site of measurable disease Inadequate cardiac function Major surgery, chemotherapy, radiotherapy, investigational agents or other cancer therapy within 1 week of treatment day 1 Active central nervous system metastases Pregnant or breastfeeding women Inability to swallow the HKI-272 capsules

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neratinib 240 mg, with prior trastuzumab<br>Neratinib administered with 80 mg capsules and 40 mg coated tablets taken orally in prescribed dose of 240 mg daily, as long as tolerated and disease does not worsen. | Drug: neratinib<br> <br> * Other names: HKI-272;|
| Experimental: Neratinib 240 mg, no prior trastuzumab<br>Neratinib administered with 80 mg capsules and 40 mg coated tablets taken orally in prescribed dose of 240 mg daily, as long as tolerated and disease does not worsen. | Drug: neratinib<br> <br> * Other names: HKI-272;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 16-week Progression Free Survival | 16 week progression-free survival (PFS) rate of neratinib in women with human epidermal growth factor receptor 2 (HER2) positive breast cancer, either with prior trastuzumab or no prior trastuzumab therapy, evaluated by independent assessment of tumor scans collected at baseline and then every 8 weeks. | From first dose to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Percentage of participants with Partial Response (PR) or Complete Response (CR) by independent assessment of tumor per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | From first dose date to progression or last tumor assessment, up to 46 months | 
| Clinical Benefit Rate | Percentage of participants who experienced Complete Response (CR), Partial Response (PR), or Stable Disease (SD) ≥ 24 weeks by independent assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. | From first dose date to progression or last tumor assessment, up to 46 months | 
| Duration of Response | Number of weeks between Complete Response (CR) or Partial Response (PR) and the first date of disease progression (PD) or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions | From start date of response to first PD/death, up to 46 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phase 2, HER2+ breast cancer, monotherapy neratinib, HKI-272, Neratinib, Nerlynx, PB-272