Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate whether neratinib can further reduce the risk of recurrence from previously diagnosed HER-2 positive breast cancer after adjuvant treatment with trastuzumab.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Trial Of Neratinib (HKI-272) After Trastuzumab In Women With Early-Stage HER-2/Neu Overexpressed/Amplified Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: neratinib
* Other: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Stage II through IIIC HER-2/erbB-2 positive breast cancer with node positive disease. Been treated for early breast cancer with standard of care duration of trastuzumab. Could have been treated neoadjuvantly but have not reached pathologic complete response. Exclusion Criteria: Positive clinical and radiologic assessments for local or regional recurrence of disease at the time of study entry. History of heart disease. Corrected QT (QTc) interval >0.45 seconds History of gastrointestinal disease with diarrhea as the 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neratinib<br>240 mg orally daily for one year | Drug: neratinib<br> <br> * Other names: Nerlynx;|
| Placebo Comparator: Placebo<br>orally daily for one year | Other: placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 2 | Invasive disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause. | From randomization until time of event up to 2 years | 
| Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms |  | From randomization until time of event up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from randomization to death due to any cause, censored at the last date known alive. | Randomization until death due to any cause (up to 119 Months) | 
| Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 2 | Disease-free survival including DCIS time is defined as the time from date of randomization until the first occurrence of DCIS or an iDFS event (an iDFS event including invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, or distant recurrence and death from any. | From randomization until time of event up to 2 years | 
| Kaplan-Meier Estimates of Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) at Year 2 by Treatment Arms |  | From randomization until time of event up to 2 years | 
| Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 2 | Distant disease-free survival time is defined as the time from date of randomization until the first occurrence of distant recurrence or death from any cause. | From randomization until time of event up to 2 years | 
| Kaplan-Meier Estimates of Distant Disease-free Survival (DDFS) at Year 2 by Treatment Arms |  | From randomization until time of event up to 2 years | 
| Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 2 | Percentage of Participants with TTDR events is reported. TTDR is defined as the time from date of randomization until the first occurrence of distant recurrence or death from breast cancer. | From randomization until time of event up to 2 years | 
| Kaplan-Meier Estimates of Time to Distant Recurrence (TTDR) Survival at Year 2 by Treatment Arms |  | From randomization until time of event up to 2 years | 
| Central Nervous System Recurrence in Neratinib Arm Compared to Placebo Arm at Year 2 | CNS recurrence is defined as the time from randomization to CNS as the first distant recurrence. Competing events include distant recurrence at other sites as the first distant recurrence and death from any cause prior to distant recurrence. | From randomization until time of event up to 2 years | 
| Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 2 | Cumulative incidence of Central Nervous System Recurrence (CNS) is estimated by Gray's method (Gray,1988). | From randomization until time of event up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HER-2/erbB-2 positive breast cancer, breast cancer, adjuvant therapy, neratinib, HKI-272, Nerlynx, PB-272