Clinical Trials /

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

NCT02163694

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: M12-914
  • SECONDARY ID: 2014-000345-70
  • NCT ID: NCT02163694

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
VeliparibABT-888Veliparib with Carboplatin and Paclitaxel
CarboplatinVeliparib with Carboplatin and Paclitaxel
PaclitaxelTaxolVeliparib with Carboplatin and Paclitaxel

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.

Trial Arms

NameTypeDescriptionInterventions
Veliparib with Carboplatin and PaclitaxelExperimentalVeliparib 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.
  • Veliparib
  • Carboplatin
  • Paclitaxel
Placebo with Carboplatin and PaclitaxelPlacebo ComparatorPlacebo 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.
  • Carboplatin
  • Paclitaxel

Eligibility 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.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Measured up to 5 years after the last subject has enrolled in the study.
Safety Issue:
Description: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

Measure:Overall survival (OS)
Time Frame:Measured up to 5 years after the last subject has enrolled in the study.
Safety Issue:
Description:Number of days from the day the subject is randomized to the date of the subject's death
Measure:Clinical benefit rate (CBR)
Time Frame:Measured up to 5 years after the last subject has enrolled in the study.
Safety Issue:
Description:Progression-free rate at 24 weeks from the Kaplan-Meier curve for time to progression
Measure:Objective response rate (ORR)
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:Proportion of subjects with a complete or partial objective response
Measure:Progression-free survival 2 (PFS2)
Time Frame:Measured up to 5 years after the last subject has enrolled in the study.
Safety Issue:
Description:Days from randomization to the second objective radiographic progression or death of any cause after the first objective radiographic progression, whichever occurs first
Measure:Duration of overall response (DOR)
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description: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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Breast Cancer
  • Carboplatin
  • BRCA2
  • BRCA Mutation
  • BRCA1
  • ABT-888
  • Paclitaxel
  • Metastatic Breast Cancer
  • PARP
  • Genetic breast cancer
  • Veliparib
  • Locally recurrent
  • PARP Inhibitor
  • HER2-negative

Last Updated

April 5, 2017