Study Evaluating Neratinib Versus Lapatinib Plus Capecitabine For ErbB2 Positive Advanced Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This is a study of an experimental drug (neratinib) versus a combination of drugs (lapatinib and capecitabine) in women who have erbB-2 (HER-2) positive metastatic or locally advanced breast cancer. The goal of this study is to compare the two regimens in shrinking tumors and extending the lives of women with erbB2 (HER2) positive breast cancer. The study will also compare the safety of the two regimens and to compare quality of life of patients taking the two regimens.

Official Title
-----------------
A Phase 2 Randomized Open-Label Study of Neratinib Versus Lapatinib Plus Capecitabine For The Treatment Of ErbB-2 Positive Locally Advanced Or Metastatic Breast Cancer

Conditions
-----------------
Advanced Breast Cancer, Breast Cancer

Intervention / Treatment
-----------------
* Drug: Neratinib
* Drug: Lapatinib
* Drug: Capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Stage IIIB, IIIC, or IV erbB2 (HER2) positive breast cancer Prior use of Herceptin (trastuzumab), and a taxane Adequate cardiac and renal function Exclusion Criteria: More than 2 prior Herceptin (trastuzumab) regimens or prior use of Xeloda (capecitabine) and / or Tykerb (lapatinib) [Tyverb] Bone as the only site of disease Active central nervous system metastases (subjects should be stable and off anticonvulsants and steroids) Significant gastrointestinal disorder with diarrhea as major symptom

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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<br> | Drug: Neratinib<br>* Tablets 240 mg orally once per day until disease progression or unacceptable toxicity<br>* Other names: HKI-272;|
| Active Comparator: Lapatinib plus Capecitabine<br> | Drug: Lapatinib<br>* Tablets 1250 mg orally once per day until disease progression or unacceptable toxicity.<br>* Other names: Tykerb, Tyverb;Drug: Capecitabine<br>* Tablets 2000 mg/m² given orally in two evenly divided daily doses for first 14 days of each 21 day cycle. Given until disease progression or unacceptable toxicity.<br>* Other names: Xeloda;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression Free Survival, Measured in Months, for Subjects Randomized. Investigator assessment. The time interval from the date of randomization until the earliest date of progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) or death due to any cause. For subjects without death or progression, censorship was at the last valid tumor assessment. | From randomization date to progression or death, assessed up to 69 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall Survival (OS) was defined as the time from randomization to death due to any cause. Subjects last known to be alive were censored at the last date of last contact or the data cutoff employed for the analysis, whichever was earlier. | From randomization date to death, assessed up to 69 months | 
| Objective Response Rate (ORR). | Objective Response Rate, investigator assessment. The ORR was defined as the percentage of participants demonstrating a confirmed objective response, either Complete Response (CR) or Partial Response (PR) during the study per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: 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 randomization date to progression or last tumor assessment, assessed up to 69 months | 
| Clinical Benefit Rate | Clinical benefit rate (CR, PR, or SD = 24 weeks) for women For ErbB2 Positive Advanced Breast Cancer. Clinical benefit rate was the percentage of subjects who achieved overall tumor 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; 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. Clinical Benefit (CB) = CR + PR + SD >= 24 weeks. | From randomization date to progression or last tumor assessment, assessed up to 69 months | 
| Duration of Response | Duration of response was measured from the time at which response criteria were met for complete response (CR) or partial response (PR) (whichever status was recorded first) until the first date of recurrence or progressive disease (PD) or death. For subjects without death or progression, censorship was at the last valid tumor assessment 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. | From start date of response to first PD, assessed up to 69 months after the first subject was randomized. | 
| Frequency of CNS Metastases (Frequency) | The percent of patients with symptomatic or progressive CNS lesions was the proportion of subjects who had PD considering CNS lesions only, according to RECIST criteria. | From randomization date to first CNS symptom or lesions | 
| Time to CNS Metastases | Time to symptomatic or progressive Central nervous system (CNS) lesions. Time to symptomatic or progressive CNS lesions was the time from the date of randomization until the date of progressive disease (PD) considering CNS lesions only (ie, appearance of newly diagnosed CNS lesions or progressive CNS lesions). | From randomization date to first CNS symptom or lesions | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HER2, ErbB2, metastatic, neratinib, lapatinib, capecitabine, HKI-272, Nerlynx, PB-272