Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors
Condition: Advanced Breast Cancer; HER2/Neu Negative; Triple-Negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Talazoparib Tosylate
Intervention description: Participants receive Talazoparib tosylate at 1 mg by mouth daily.
Intervention MeSH terms: Talazoparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PALB2 mutation; BRIP1 mutation; BARD1 mutation; Rad51c mutation; PTEN mutation; CHEK2 mutation; ATM mutation; NBN mutation; Rad51d mutation; Rad50 mutation; MRE11 mutation; FANC mutation; HRD assay score; ATR mutation

Summary:

      The aim of this single-arm phase 2 clinical trial is to evaluate the anti-cancer activity of
      Talazoparib (also known as BMN 673) in patients with advanced breast cancer with specific
      genetic or tumor genomic alterations. Patients with either triple-negative or HER2-negative
      breast cancer are eligible.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  No deleterious germline BRCA1 or BRCA2 mutation based on full sequencing and
             comprehensive rearrangement testing at an external reference laboratory; patients with
             variants of unknown significance will be eligible

          -  Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version
             1.1

          -  Must have progressed on at least 1 prior chemotherapy regimen for the treatment of
             advanced breast cancer; there is no upper limit on the number of prior therapies

          -  If prior platinum agent (eg, carboplatin or cisplatin) has been administered, no
             evidence of progression, or within 8 weeks of stopping platinum treatment

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

          -  Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x
             upper limit of normal (ULN); if liver function abnormalities are due to hepatic
             metastasis, then AST and ALT ≤ 5 x ULN

          -  Total serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN for Gilbert's syndrome)

          -  Calculated creatinine clearance ≥ 30 mL/min or serum creatinine ≤ 1.5 mg/dL

          -  Hemoglobin ≥ 9.0 g/dL with last transfusion at least 14 days before day 1 of study
             drug

          -  Absolute neutrophil count (ANC) ≥ 1500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Able to take oral medications

          -  Willing and able to provide written, signed informed consent after the nature of the
             study has been explained, and prior to any research-related procedures

          -  Sexually active patients of childbearing potential must be willing to use an
             acceptable method of contraception such as an intrauterine device or double barrier
             contraception during treatment and for 30 days after the last dose of study drug

          -  Females of childbearing potential must have a negative serum pregnancy test at
             screening and be willing to have additional serum pregnancy tests during the study;
             females considered not of childbearing potential include those who have been in
             menopause at least 2 years, or had tubal ligation at least 1 year prior to screening,
             or who have had total hysterectomy

          -  Willing and able to comply with all study procedures

          -  COHORT A SPECIFIC ELIGIBILITY CRITERIA:

               -  Histologically-confirmed metastatic or recurrent triple-negative breast cancer
                  (defined as estrogen receptor ≤ 5%, progesterone receptor ≤ 5%, HER2-negative via
                  immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH])

               -  An homologous recombination deficiency (HRD) score ≥ 42 on the HRD Assay as
                  assessed on a tumor biopsy sample; in the case that obtaining an adequate
                  metastatic tumor biopsy is not possible, we will assess the HRD score from the
                  primary breast tumor

          -  COHORT B SPECIFIC ELIGIBILITY CRITERIA:

               -  Histologically-confirmed metastatic or recurrent HER2-negative (via IHC or FISH)
                  breast cancer or other histologically-confirmed metastatic solid tumor

               -  Deleterious germline or somatic mutation implicated in the homologous
                  recombination (HR) pathway, excluding BRCA1 or BRCA2, based on germline multiplex
                  gene testing or direct tumor next generation DNA sequencing. Genes of interest
                  include: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, Rad51c, Rad51d,
                  MRE11, ATR, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, plus other
                  HR-related genes at the discretion of the primary investigators.

        EXCLUSION CRITERIA:

          -  Any patient with a deleterious mutation in BRCA1 or BRCA2

          -  Hormone receptor positive and/or HER2 positive breast cancer (Cohort A only)

          -  HER2 positive breast cancer (Cohort B only)

          -  Prior treatment with a PARP inhibitor

          -  Non-measurable disease only

          -  Pregnant or nursing patients

          -  Any anti-cancer therapy within the past 21 days of the first day of treatment

          -  Brain or central nervous system (CNS) metastases

               -  Exception: Adequately treated brain metastases documented by baseline computed
                  tomography (CT) or magnetic resonance imaging (MRI) scan that have not progressed
                  since previous scans and do not require corticosteroids (except prednisone ≤ 5
                  mg/day or equivalent) for management of CNS symptoms. A repeated CT or MRI
                  following the identification of CNS metastases (obtained at least 2 weeks after
                  definitive therapy) must document adequately treated brain metastases

               -  Subjects with leptomeningeal carcinomatosis are not permitted

          -  Other malignancy that is either active or for which patient has received treatment in
             the last five years excluding non-melanoma skin cancer and carcinoma in situ of the
             cervix

          -  Radiation therapy in the last 14 days

          -  Known to be human immunodeficiency virus positive

          -  Known active hepatitis C virus

          -  Known active hepatitis B virus

          -  Use of any investigational product or investigational medical device within 28 days
             before day 1 of study drug

          -  Major surgery requiring a prolonged hospitalization or recovery within 21 days before
             day 1 of study drug

          -  Concurrent disease or condition that would interfere with study participation or
             safety, such as any of the following:

               -  Active, clinically significant infection either grade > 2 by National Cancer
                  Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version
                  4.0 or requiring the use of parenteral anti-microbial agents within 7 days before
                  day 1 of study drug

               -  Clinically significant bleeding diathesis or coagulopathy, including known
                  platelet function disorders

               -  Known hypersensitivity to any of the components of BMN 673