A Study Evaluating Safety and Efficacy of the Addition of ABT-888 Plus Carboplatin Versus the Addition of Carboplatin to Standard Chemotherapy Versus Standard Chemotherapy in Subjects With Early Stage Triple Negative Breast Cancer

Study Overview
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Brief Summary
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This is a 3 arm Phase 3 study to evaluate the safety and efficacy of the addition of veliparib plus carboplatin versus the addition of carboplatin to standard neoadjuvant chemotherapy versus standard neoadjuvant chemotherapy in subjects with early stage TNBC.

Official Title
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A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study Evaluating Safety and Efficacy of the Addition of Veliparib Plus Carboplatin Versus the Addition of Carboplatin to Standard Neoadjuvant Chemotherapy Versus Standard Neoadjuvant Chemotherapy in Subjects With Early Stage Triple Negative Breast Cancer (TNBC)

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Placebo
* Drug: Doxorubicin
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Veliparib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive breast cancer by core needle or incisional biopsy (excisional biopsy is not allowed). Clinical stage T2-3 N0-2 or T1 N1-2 by physical exam or radiologic studies. Documented Breast Cancer Gene (BRCA) germline mutation testing. Estrogen Receptor (ER)-, Progesterone Receptor (PR)-, and Human Epidermal Growth Factor Receptor (HER)2-negative (triple-negative) cancer of the breast. ECOG Performance status of 0 to 1. Women must be determined to be not of childbearing potential (surgically sterile, or postmenopausal defined as amenorrheic for at least 12 months) by the Investigator OR they must have a negative serum pregnancy test prior to randomization. Exclusion Criteria: Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic therapy radiotherapy or investigational agents) with therapeutic intent for current breast cancer. Previous treatment with carboplatin, paclitaxel, doxorubicin, cyclophosphamide and a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor. Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Subjects must have discontinued use of such agents prior to beginning study treatment. A history of seizure within 12 months prior to study entry. Pre-existing neuropathy from any cause in excess of Grade 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC) | Drug: Cyclophosphamide<br>* Cyclophosphamide<br>Drug: Doxorubicin<br>* Doxorubicin<br>Drug: Paclitaxel<br>* Paclitaxel<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Veliparib<br>* Veliparib<br>* Other names: ABT-888;|
| Placebo Comparator: Arm C<br>Placebo + placebo + paclitaxel followed by AC. | Drug: Cyclophosphamide<br>* Cyclophosphamide<br>Drug: Placebo<br>* Placebo for Carboplatin<br>Drug: Doxorubicin<br>* Doxorubicin<br>Drug: Paclitaxel<br>* Paclitaxel<br>Drug: Placebo<br>* Placebo for Veliparib<br>|
| Placebo Comparator: Arm B<br>Placebo + carboplatin + paclitaxel followed by AC | Drug: Cyclophosphamide<br>* Cyclophosphamide<br>Drug: Doxorubicin<br>* Doxorubicin<br>Drug: Paclitaxel<br>* Paclitaxel<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Placebo<br>* Placebo for Veliparib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR). | Pathological complete response (pCR) in the breast tissue and the lymph node tissue will be assessed upon completion of pre-operative systemic therapy and definitive surgery. | At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival (EFS) | EFS will be defined as the time from random assignment to documentation of the first of the following events: discontinuation of study therapy due to protocol-defined progression prior to surgery; local, regional, or distant recurrence of breast cancer following curative surgery; a new breast cancer; another new onset malignancy; or death as a result of any cause. | Up to 4 years from the date of definitive surgery. | 
| Overall Survival (OS) | OS will be defined as the number of days from the day the subject is randomized to the date of the subject's death. | Up to 4 years from the date of definitive surgery. | 
| Rate of eligibility for breast conservation after therapy (BCR). | Whether a subject is eligible for breast conserving surgery for whom mastectomy was planned at diagnosis will be determined by the subject's surgeon prior to chemotherapy and after completion of chemotherapy. | At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alliance - AFT-04, Oncology, Triple negative breast cancer, German Breast Group - GBG 81, United States Oncology - 12152, National Surgical Adjuvant Breast and Bowel Project - B-56-I, Grupo Español de Investigación en Cáncer de Mama - GEICAM/2014-02