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A Phase 3 Randomized, Placebo-controlled Trial of Carboplatin and Paclitaxel With or Without Veliparib (ABT-888) in HER2-negative Metastatic or Locally Advanced Unresectable BRCA-associated Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by AbbVie
Sponsor:
Information provided by (Responsible Party):
AbbVie
ClinicalTrials.gov Identifier:
NCT02163694
First received: May 19, 2014
Last updated: October 6, 2016
Last verified: October 2016
  Purpose
The study seeks to evaluate the efficacy and tolerability of veliparib/placebo in combination with carboplatin and paclitaxel in HER2-negative metastatic or locally advanced, unresectable, BRCA-associated breast cancer.

Condition Intervention Phase
Metastatic Breast Cancer
Drug: Veliparib
Drug: Carboplatin
Drug: Paclitaxel
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2 Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Number of days from the date the subject is randomized to the date the subject experiences a confirmed event of disease progression or to the date of death if disease progression is not reached


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Number of days from the day the subject is randomized to the date of the subject's death

  • Clinical benefit rate (CBR) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Progression-free rate at 24 weeks from the Kaplan-Meier curve for time to progression

  • Objective response rate (ORR) [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Proportion of subjects with a complete or partial objective response

  • Progression-free survival 2 (PFS2) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Days from randomization to the second objective radiographic progression or death of any cause after the first objective radiographic progression, whichever occurs first

  • Duration of overall response (DOR) [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Number of days from the day the criteria are met for complete response or partial response (whichever is recorded first) to the date of progressive disease


Other Outcome Measures:
  • Change in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Change in ECOG performance status

  • Change in quality of life (QOL) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Assessed via survey


Estimated Enrollment: 500
Study Start Date: July 2014
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Veliparib with Carboplatin and Paclitaxel
Veliparib on Day -2 through 5 of a 21-day cycle. In addition, carboplatin and paclitaxel will be administered on Day 1 of a 21-day cycle.
Drug: Veliparib
Veliparib on Day -2 through 5 of a 21-day cycle. In addition, carboplatin and paclitaxel will be administered on Day 1 of a 21-day cycle.
Other Name: ABT-888
Drug: Carboplatin
Day 1 of 21-day cycle
Drug: Paclitaxel
Day 1 of 21-day cycle
Other Name: Taxol
Placebo Comparator: Placebo with Carboplatin and Paclitaxel
Placebo on Day -2 through 5 of a 21-day cycle. In addition, carboplatin and paclitaxel will be administered on Day 1 of a 21-day cycle.
Drug: Carboplatin
Day 1 of 21-day cycle
Drug: Paclitaxel
Day 1 of 21-day cycle
Other Name: Taxol
Other: Placebo
Placebo on Day -2 through 5 of a 21-day cycle. In addition, carboplatin and paclitaxel will be administered on Day 1 of a 21-day cycle.

  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed breast cancer that is either locally advanced or metastatic. Locally advanced breast cancer must not be amenable to surgical resection or radiation with curative intent.
  2. Suspected deleterious or deleterious BRCA1 and/or BRCA2 germline mutation.
  3. Breast cancer must be HER2-negative.
  4. Measurable or non-measurable (but radiologically evaluable) disease per Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1 on computed tomography (CT) scan (within 28 days of randomization) with at least one lesion outside previously irradiated areas.
  5. ECOG Performance status of 0 to 2.
  6. Adequate hematologic, renal, and hepatic function (within 28 days of randomization).

Exclusion Criteria:

  1. More than two prior lines of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin, capecitabine) for metastatic disease.

    • Regimens received in the adjuvant/neoadjuvant setting or for locally advanced breast cancer within the past 6 months will also be considered toward the maximum of 2 prior lines of therapy. Adjuvant/neoadjuvant chemotherapy for one cancer event will count as one prior line of therapy, if received within the past 6 months.
    • Previous treatments with hormonal therapy (tamoxifen, aromatase inhibitors) and signal transduction agents (e.g., erlotinib, gefitinib, everolimus, bevacizumab) are allowed and are not counted towards the prior line of therapy.
  2. Progressed or recurred within 12 months of completing platinum therapy or received > 1 prior line of platinum therapy for breast cancer in any setting (adjuvant or neoadjuvant).
  3. Prior therapy with PARP inhibitors.
  4. Prior taxane therapy administered for the treatment of metastatic breast cancer with the below exceptions.

    • Prior taxane therapy for metastatic breast cancer is allowed if the patient received ≤ 1 full cycle (i.e., therapy discontinued within 4 weeks for subjects receiving weekly paclitaxel or Abraxane; therapy discontinued within 3 weeks for subjects receiving paclitaxel or docetaxel every 3 weeks) in the absence of progression or if taxane therapy for metastatic disease was > 12 months prior to C1D-2.
    • Use of taxanes as adjuvant therapy or to treat locally advanced disease is permitted, if given more than 6 months prior to C1D-2
  5. Known history of allergic reaction to cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.
  6. Active CNS metastases or leptomeningeal disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02163694

Contacts
Contact: Andrew Coates, BS 847-937-8266 andrew.coates@abbvie.com
Contact: Melissa Shah, BS (847) 938-3885 melissa.shah@abbvie.com

  Show 239 Study Locations
Sponsors and Collaborators
AbbVie
Investigators
Study Director: Ewelina Morawa, MD AbbVie
  More Information

Additional Information:
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02163694     History of Changes
Other Study ID Numbers: M12-914  2014-000345-70 
Study First Received: May 19, 2014
Last Updated: October 6, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
Breast Cancer
Carboplatin
BRCA2
BRCA Mutation
BRCA1
ABT-888
Paclitaxel
Metastatic Breast Cancer
PARP
Genetic breast cancer
Veliparib
Locally recurrent
PARP Inhibitor
HER2-negative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Veliparib
Albumin-Bound Paclitaxel
Carboplatin
Poly(ADP-ribose) Polymerase Inhibitors
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

ClinicalTrials.gov processed this record on December 02, 2016