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
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Veliparib Placebo; Veliparib; Carboplatin; Paclitaxel
Intervention description: Supplied as 40 mg, 50 mg, or 100 mg capsules for oral administration twice daily (BID) on Days -2 through 5 of a 21-day cycle.; Supplied as 40 mg, 50 mg, or 100 mg capsules for oral administration twice daily (BID) on Days -2 through 5 of a 21-day cycle.; Administered intravenously over approximately 15 to 30 minutes at an area under the curve (AUC) of 6 mg/mL/min immediately following paclitaxel infusion on Day 1 of every cycle. The duration of carboplatin infusion may be lengthened according to institutional guidelines.; Administered by intravenous infusion over approximately 1 hour at a dose of 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel is to be infused prior to carboplatin on Day 1. Dosing of veliparib/placebo is to be completed before the carboplatin or paclitaxel infusions.
Intervention MeSH terms: Paclitaxel; Carboplatin; Veliparib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 509.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PARP Inhibitor; Veliparib; BRCA1; BRCA2; HER2-negative; Locally recurrent; Breast Cancer; Metastatic Breast Cancer; ABT-888; Genetic breast cancer; Paclitaxel; BRCA Mutation; PARP; Carboplatin; BROCADE3

Summary:

      The primary objective of the study is to assess the progression-free survival (PFS) of
      veliparib in combination with carboplatin and paclitaxel (C/P) compared to placebo plus C/P
      in participants with a Breast Cancer Gene 1 or 2 (BRCA1; BRCA2) mutation in Human Epidermal
      Growth Factor Receptor 2 (HER2)-negative metastatic or locally advanced unresectable breast
      cancer. The secondary objectives of the study are to assess overall survival (OS), clinical
      benefit rate (CBR) through the end of Week 24, objective response rate (ORR) and PFS on
      subsequent therapy (PFS2) in participants treated with veliparib in combination with C/P
      versus placebo in combination with C/P.
    

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 Breast Cancer Gene 1 (BRCA1) and/or Breast Cancer
             Gene 2 (BRCA2) germline mutation.

          3. Breast cancer must be Human Epidermal Growth Factor Receptor 2 (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. Eastern Cooperative Oncology Group (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,
             neoadjuvant, or metastatic).

          3. Prior therapy with Poly(ADP-ribose)-Polymerase (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
                  Cycle 1 Day-2 (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.