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)
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- AbbVie
- Enrollment
- 634
- Locations
- 158
- Primary Endpoint
- Pathological Complete Response (pCR).
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
- •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.
Arms & Interventions
Arm C
Placebo + placebo + paclitaxel followed by AC.
Intervention: Placebo
Arm C
Placebo + placebo + paclitaxel followed by AC.
Intervention: Doxorubicin
Arm A
Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC)
Intervention: Cyclophosphamide
Arm A
Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC)
Intervention: Doxorubicin
Arm A
Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC)
Intervention: Paclitaxel
Arm A
Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC)
Intervention: Carboplatin
Arm A
Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC)
Intervention: Veliparib
Arm C
Placebo + placebo + paclitaxel followed by AC.
Intervention: Cyclophosphamide
Arm C
Placebo + placebo + paclitaxel followed by AC.
Intervention: Paclitaxel
Arm B
Placebo + carboplatin + paclitaxel followed by AC
Intervention: Cyclophosphamide
Arm B
Placebo + carboplatin + paclitaxel followed by AC
Intervention: Doxorubicin
Arm B
Placebo + carboplatin + paclitaxel followed by AC
Intervention: Paclitaxel
Arm B
Placebo + carboplatin + paclitaxel followed by AC
Intervention: Carboplatin
Arm B
Placebo + carboplatin + paclitaxel followed by AC
Intervention: Placebo
Outcomes
Primary Outcomes
Pathological Complete Response (pCR).
Time Frame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug).
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.
Secondary Outcomes
- Event Free Survival (EFS)(Up to 4 years from the date of definitive surgery.)
- Overall Survival (OS)(Up to 4 years from the date of definitive surgery.)
- Rate of eligibility for breast conservation after therapy (BCR).(At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug).)