Study Evaluating Neratinib Plus Paclitaxel VS Trastuzumab Plus Paclitaxel In ErbB-2 Positive Advanced Breast Cancer

Study Overview
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Brief Summary
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This study is investigating the effects of an experimental drug (neratinib) in combination with paclitaxel versus trastuzumab in combination with paclitaxel for the treatment of women who have not received previous treatment for erbB-2-positive locally recurrent or metastatic breast cancer. The study will compare the effectiveness of each regimen in shrinking tumors and extending the lives of women with erbB-2 (HER2) positive breast cancer. The study will also compare the safety of the two regimens and as well as the quality of life of subjects receiving either regimen.

Official Title
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A Randomized, Open-Label, Two-Arm Study Of Neratinib Plus Paclitaxel Versus Trastuzumab Plus Paclitaxel As First-Line Treatment For ErbB-2-Positive Locally Recurrent Or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Neratinib
* Drug: Trastuzumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ErbB-2 positive locally recurrent or metastatic breast cancer Eastern Cooperative Oncology Group (ECOG) 0-2 Measurable disease Availability of tumor tissue for HER2 status confirmation Exclusion Criteria: Prior systemic anti-cancer therapy other than endocrine therapy for locally recurrent or metastatic disease Prior erbB-2 inhibitor other than trastuzumab or lapatinib in the neoadjuvant or adjuvant setting Progression/recurrence within 12 months after completion of adjuvant or neoadjuvant therapy History of heart disease History of gastrointestinal disease

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 plus paclitaxel<br> | Drug: Neratinib<br>* Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.<br>Drug: Paclitaxel<br>* Paclitaxel - 80 mg/m² IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.<br>* Other names: Nov-onxol;|
| Active Comparator: trastuzumab plus paclitaxel<br> | Drug: Trastuzumab<br>* Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.<br>* Other names: Herclon;Drug: Paclitaxel<br>* Paclitaxel - 80 mg/m² IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.<br>* Other names: Nov-onxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | 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. | From randomization to disease progression or death, assessed up to 5.3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Defined as the percentage of subjects who achieved confirmed tumor response (complete or partial response) 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-Progressive Disease for non-target lesions, and no new lesions. | From randomization to disease progression or last tumor assessment, assessed up to 5.3 years | 
| Duration of Response | 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, disease progression (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 first response to first PD or death, assessed up to 5.3 years after first subject randomized | 
| Clinical Benefit Rate | Defined as the proportion of patients who achieved overall tumor response (CR or PR) or SD for at least 24 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 randomization to disease progression or death, assessed up to 5.3 years | 
| Symptomatic or Progressive Central Nervous System (CNS) Lesions | Defined as the time interval from the date of randomization until the first date of CNS symptoms, the imaging examination shows CNS progression or is censored at the last assessable evaluation on study or prior to new anti-cancer therapy, if applicable. If median time to Symptomatic or Progressive CNS Lesions is not estimable, cumulative incidence will be reported instead. | From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ErbB-2 positive advanced breast cancer, HKI-272, Neratinib, Nerlynx, HER2, PB-272, metastatic breast cancer