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

• ClinicalTrials.gov Identifier: NCT02032277
• Recruitment Status: Completed
• First Posted: January 10, 2014
• Last Update Posted: January 20, 2021
• Sponsor: AbbVie
• Collaborators: German Breast Group; NSABP Foundation Inc; Grupo Español de Investigación del Cáncer de Mama; US Oncology Research
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: December 13, 2013
• First Posted Date: January 10, 2014
• Last Update Posted Date: January 20, 2021
• Actual Study Start Date: April 2, 2014
• Actual Primary Completion Date: March 18, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 8, 2018)

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.

Original Primary Outcome Measures (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.

Current Secondary Outcome Measures (submitted: July 8, 2020)

• Event Free Survival (EFS) [ Time Frame: Up to 4 years from the date of definitive surgery. ]
  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.
• Overall Survival (OS) [ Time Frame: Up to 4 years from the date of definitive surgery. ]
  OS will be defined as the number of days from the day the subject is randomized to the date of the subject's death.
• 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 for whom mastectomy was planned at diagnosis will be determined by the subject's surgeon prior to chemotherapy and after completion of chemotherapy.

Original Secondary Outcome Measures (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 Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (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: 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: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Triple Negative Breast Cancer

Intervention

• Drug: Cyclophosphamide
  Cyclophosphamide
• Drug: Placebo
  Placebo for Carboplatin
• Drug: Doxorubicin
  Doxorubicin
• Drug: Paclitaxel
  Paclitaxel
• Drug: Carboplatin
  Carboplatin
• Drug: Veliparib
  Veliparib
  Other Name: ABT-888
• 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 *

• Filho OM, Stover DG, Asad S, Ansell PJ, Watson M, Loibl S, Geyer CE Jr, Bae J, Collier K, Cherian M, O'Shaughnessy J, Untch M, Rugo HS, Huober JB, Golshan M, Sikov WM, von Minckwitz G, Rastogi P, Maag D, Wolmark N, Denkert C, Symmans WF. Association of Immunophenotype With Pathologic Complete Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: A Secondary Analysis of the BrighTNess Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):603-608. doi: 10.1001/jamaoncol.2020.7310.
• Golshan M, Loibl S, Wong SM, Houber JB, O'Shaughnessy J, Rugo HS, Wolmark N, McKee MD, Maag D, Sullivan DM, Metzger-Filho O, Von Minckwitz G, Geyer CE Jr, Sikov WM, Untch M. Breast Conservation After Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Surgical Results From the BrighTNess Randomized Clinical Trial. JAMA Surg. 2020 Mar 1;155(3):e195410. doi: 10.1001/jamasurg.2019.5410. Epub 2020 Mar 18. Erratum In: JAMA Surg. 2021 May 1;156(5):503.
• Golshan M, Wong SM, Loibl S, Huober JB, O'Shaughnessy J, Rugo HS, Wolmark N, Ansell P, Maag D, Sullivan DM, Metzger-Filho O, Von Minckwitz G, Geyer CE Jr, Sikov WM, Untch M. Early assessment with magnetic resonance imaging for prediction of pathologic response to neoadjuvant chemotherapy in triple-negative breast cancer: Results from the phase III BrighTNess trial. Eur J Surg Oncol. 2020 Feb;46(2):223-228. doi: 10.1016/j.ejso.2019.10.002. Epub 2019 Oct 5.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 12, 2018): 634
• Original Estimated Enrollment (submitted: January 8, 2014): 624
• Actual Study Completion Date: November 12, 2020
• Actual Primary Completion Date: March 18, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 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.
2. Documented Breast Cancer Gene (BRCA) germline mutation testing.
3. Estrogen Receptor (ER)-, Progesterone Receptor (PR)-, and Human Epidermal Growth Factor Receptor (HER)2-negative (triple-negative) cancer of the breast.
4. ECOG Performance status of 0 to 1.
5. 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:

1. Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic therapy radiotherapy or investigational agents) with therapeutic intent for current breast cancer.
2. Previous treatment with carboplatin, paclitaxel, doxorubicin, cyclophosphamide and a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.
3. 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.
4. A history of seizure within 12 months prior to study entry.
5. 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, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT02032277
• Other Study ID Numbers: 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: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current

Collaborators

• German Breast Group
• NSABP Foundation Inc
• Grupo Español de Investigación del Cáncer de Mama
• US Oncology Research

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: January 2021