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

Tracking Information
First Submitted Date ICMJE	December 13, 2013
First Posted Date ICMJE	January 10, 2014
Last Update Posted Date	January 17, 2018
Actual Study Start Date ICMJE	April 2, 2014
Actual Primary Completion Date	March 18, 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 8, 2014)	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. Subjects who do not complete definitive surgery for reasons other than withdrawal of consent will be considered not to have achieved pCR.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT02032277 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 12, 2018)	Event Free Survival (EFS) [ Time Frame: Up to 10 years from first dose of study drug. ]EFS will be defined as the time from random assignment to documentation of the first of the following events: failure to reach potential curative surgery; local, regional, or distant invasive recurrence of breast cancer following curative surgery; a contralateral breast cancer; a new onset malignancy; or death as a result of any cause.; Rate of eligibility for breast conservation after therapy (BCR). [ Time Frame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). ]Whether a subject is eligible for breast conserving surgery will be determined by the subject's surgeon prior to chemotherapy and after completion of chemotherapy.; Overall Survival (OS) [ Time Frame: Up to 10 years from first dose of study drug. ]OS will be defined as the number of days from the day the subject is randomized to the date of the subject's death.
Original Secondary Outcome Measures ICMJE; (submitted: January 8, 2014)	Rate of eligibility for breast conservation after therapy (BCR). [ Time Frame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). ]; Whether a subject is eligible for breast conserving surgery will be determined by the subject's surgeon prior to chemotherapy and after completion of chemotherapy.
Current Other Outcome Measures ICMJE; (submitted: January 12, 2018)	Breast cancer related quality of life (QoL). [ Time Frame: First day of treatment (Day 1) up to 6 months during the post-surgery follow-up period (approximately 15 months from first dose of study drug). ]Breast cancer related QoL will be assessed via the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), Breast Cancer module (EORTC QLQ-BR23) and European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) questionnaires.; Eastern Cooperative Oncology Group (ECOG) performance status. [ Time Frame: First day of treatment (Day 1) to Pre-Op Visit (approximately 22-32 weeks from first dose of study drug). ]ECOG performance status will be determined by the Investigator at each assessment.; pCR plus minimal residual disease (defined as residual cancer burden [RCB] class I) [ Time Frame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). ]RCB in the breast tissue and the lymph node tissue will be assessed upon completion of pre-operative systemic therapy and definitive surgery.; Clinical Response Rate (CRR) [ Time Frame: First day of treatment on Chemotherapy Segment 2 (approximately 12-16 weeks from first dose of study drug). ]CRR at 12 weeks and tumor sizes at 12 weeks will be summarized at the end of the Chemotherapy Segment 1 of the treatment (reported at visit AC1) to assess the objective response rate. CRR is defined as the proportion of subjects with complete or partial response of the primary tumor as determined by the central imaging vendor.
Original Other Outcome Measures ICMJE; (submitted: January 8, 2014)	Event Free Survival (EFS) [ Time Frame: Up to 10 years from first dose of study drug. ]EFS will be defined as the time from random assignment to documentation of the first of the following events: failure to reach potential curative surgery; local, regional, or distant invasive recurrence of breast cancer following curative surgery; a contralateral breast cancer; a new onset malignancy; or death as a result of any cause.; Overall Survival (OS) [ Time Frame: Up to 10 years from first dose of study drug. ]OS will be defined as the number of days from the day the subject is randomized to the date of the subject's death.; Clinical Response Rate (CRR) [ Time Frame: First day of treatment on Chemotherapy Segment 2 (approximately 12-16 weeks from first dose of study drug). ]CRR at 12 weeks and tumor sizes at 12 weeks will be summarized at the end of the Chemotherapy Segment 1 of the treatment (reported at visit AC1) to assess the objective response rate. CRR is defined as the proportion of subjects with complete or partial response of the primary tumor as determined by the central imaging vendor.; pCR plus minimal residual disease (defined as residual cancer burden [RCB] class I) [ Time Frame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug). ]RCB in the breast tissue and the lymph node tissue will be assessed upon completion of pre-operative systemic therapy and definitive surgery.; Eastern Cooperative Oncology Group (ECOG) performance status. [ Time Frame: First day of treatment (Day 1) to Pre-Op Visit (approximately 22-32 weeks from first dose of study drug). ]ECOG performance status will be determined by the Investigator at each assessment.; Breast cancer related quality of life (QoL). [ Time Frame: First day of treatment (Day 1) up to 6 months during the post-surgery follow-up period (approximately 15 months from first dose of study drug). ]Breast cancer related QoL will be assessed via the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), Breast Cancer module (EORTC QLQ-BR23) and European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) questionnaires.
Descriptive Information
Brief Title ICMJE	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
Official Title ICMJE	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)
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Triple Negative Breast Cancer
Intervention ICMJE	Drug: Cyclophosphamide Cyclophosphamide; Drug: Placebo Placebo for Carboplatin; Drug: Doxorubicin Doxorubicin; Drug: Paclitaxel Paclitaxel; Drug: Carboplatin Carboplatin; Drug: Veliparib Veliparib; Drug: Placebo Placebo for Veliparib
Study Arms	Active Comparator: Arm A Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC) Interventions: Drug: Cyclophosphamide Drug: Doxorubicin Drug: Paclitaxel Drug: Carboplatin Drug: Veliparib; Placebo Comparator: Arm C Placebo + placebo + paclitaxel followed by AC. Interventions: Drug: Cyclophosphamide Drug: Placebo Drug: Doxorubicin Drug: Paclitaxel Drug: Placebo; Placebo Comparator: Arm B Placebo + carboplatin + paclitaxel followed by AC Interventions: Drug: Cyclophosphamide Drug: Doxorubicin Drug: Paclitaxel Drug: Carboplatin Drug: Placebo
Publications *	Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):497-509. doi: 10.1016/S1470-2045(18)30111-6. Epub 2018 Feb 28.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: January 12, 2018)	634
Original Estimated Enrollment ICMJE; (submitted: January 8, 2014)	624
Estimated Study Completion Date	November 2, 2020
Actual Primary Completion Date	March 18, 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histologically confirmed invasive breast cancer by core needle or incisional biopsy (excisional biopsy is not allowed). Tumors must be clinical stage T2-3 N0-2 or T1 N1-2 per AJCC Staging Edition 7 or 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.
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years to 99 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Korea, Republic of, Netherlands, Russian Federation, Spain, Taiwan, United Kingdom, United States
Removed Location Countries	Czech Republic, Israel, Poland
Administrative Information
NCT Number ICMJE	NCT02032277
Other Study ID Numbers ICMJE	M14-011; 2013-002377-21 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement	Plan to Share IPD: No
Responsible Party	AbbVie
Study Sponsor ICMJE	AbbVie
Collaborators ICMJE	German Breast Group; NSABP Foundation Inc; Grupo Español de Investigación del Cáncer de Mama; US Oncology Research; Alliance for Clinical Trials in Oncology
Investigators ICMJE	Study Director: AbbVie Inc. AbbVie
PRS Account	AbbVie
Verification Date	January 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP