Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer
Condition: Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Paclitaxel; Carboplatin; Doxorubicin; Cyclophosphamide; Veliparib
Intervention description: Given IV; Given IV; Given IV; Given IV; Given PO
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Carboplatin; Doxorubicin; Liposomal doxorubicin; Veliparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well carboplatin and combination chemotherapy with
      or without veliparib works in treating patients with stage IIB-IIIC breast cancer. Drugs used
      in chemotherapy, such as paclitaxel, carboplatin, doxorubicin hydrochloride, and
      cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing
      the cells or by stopping them from dividing. Veliparib may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth. It is not yet known whether giving
      carboplatin and combination chemotherapy are more effective with or without veliparib is more
      effective in treating breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent must be obtained prior to any study-related procedures.

          2. Histologically confirmed adenocarcinoma of the breast with the following markers:
             Estrogen receptor negative (<1%), progesterone receptor negative (<1%), and Her-2/neu
             negative (Her-2/neu 0-1+ IHC or FISH ratio <1.8 or average HER2 gene copy number of
             <four signal/nucleus for test systems without internal control probe).

          3. Female ≥ 18 years old.

          4. Clinical stage IIA (T2N0), IIB (T2N1, T3N0) or stage IIIA (T1N2, T2N2, T3N1, T3N2),
             IIIB, or IIIC breast cancer with no prior treatment.

          5. Complete radiology or tumor assessment within 28 days prior to enrollment

               1. Breast MRI

               2. Unilateral Breast Ultrasound

               3. Distant metastatic work-up completed with PET/CT.

               4. If enlarged axillary lymph nodes are found during staging scans, FNA must be
                  performed to determine whether the node is involved with cancer.

               5. If axillary lymph nodes are clinically negative during initial work-up, sentinel
                  node biopsy will be performed prior to initiation of chemotherapy.

          6. ECOG Performance Status of 0 or 1

          7. Adequate organ and hematologic function as evidenced by the following laboratory
             studies within 4 weeks of study enrollment:

               1. Cardiac Ejection Fraction >/= lower limit of normal as determined by 2-D echo or
                  MUGA scan according to institutional standards.

               2. Hematologic function, as follows: Absolute neutrophil count ≥ 1.5 x 109/L,
                  Platelet count ≥ 100 x 109/L and ≤ 850 x 109/L, Hemoglobin ≥ 9 g/dL, PTT and INR
                  < 1.5 x ULN.

               3. Renal function, as follows: Serum creatinine </= 1.4 mg/dL).

               4. Hepatic function, as follows:Aspartate aminotransferase (AST) ≤ 2.5 x ULN,
                  Alanine aminotransferase (ALT) ≤ 2.5 x ULN , Total bilirubin ≤ 2 x ULN (except
                  for patients with UGT1A1 promoter polymorphism, i.e. Gilbert syndrome, confirmed
                  by genotyping or Invader UGT1A1 molecular assay prior to study enrollment.
                  Patients enrolled with Gilbert syndrome must have total bilirubin < 3 ULN).

          8. Patient must be willing and able to undergo MRI as outlined in protocol.

        Exclusion Criteria:

          1. Known hypersensitivity to doxorubicin, cyclophosphamide, paclitaxel, cremophor or
             medications containing cremophor(miconazole, docetaxel, sandimmune, nelfinavir
             mesylate, propofol, diazepam injection, vitamin K injection, ixabepilone, aci-jel) or
             carboplatin.

          2. Known HIV or active Hepatitis B or C infection.

          3. Prior treatment for the currently diagnosed breast cancer.

          4. Prior treatment with doxorubicin up to 400 mg/m2.

          5. Pre-existing Grade 3 or 4 sensory neuropathy.

          6. History of bleeding diathesis or extensive bleeding requiring blood transfusion within
             14 days of enrollment.

          7. Major surgical procedure within 4 weeks (28 days) prior to enrollment (port placement
             is not considered a major surgical procedure).

          8. Clinically significant cardiac disease within 12 months of study enrollment, including
             myocardial infarction, unstable angina, congestive heart failure, or ongoing
             arrhythmias requiring medication or pacemaker.

          9. Non-healing wound, ulcer or fracture.

         10. Ongoing or active infection.

         11. Pregnant (i.e., positive beta-human chorionic gonadotropin test) or lactating

         12. Not willing to use a highly effective method of birth control (i.e. those which result
             in low failure rates, less than 1% per year), defined as intrauterine devices, barrier
             methods (condoms, contraceptive sponges, diaphragms, vaginal rings used with
             spermicidal jellies or creams), oral contraceptive pills, or sexual abstinence.
             Contraception must be used during the study.

         13. T0 tumors

         14. Active dental infection