Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer
Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer
A PHASE 2, NON RANDOMIZED, OPEN LABEL, SINGLE ARM, MULTI CENTER STUDY OF TALAZOPARIB FOR
 NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH
 FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER
TALAZOPARIB (PARP INHIBITOR) FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS
 WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER. THIS IS A
 MONOTHERAPY TREATMENT FOR 24 WKS FOLLOWED BY SURGERY TO EVALUATE PATHOLOGICAL COMPLETE
 RESPONSE.
Inclusion Criteria:

 -  Germline BRCA 1/2 Mutation Positive

 -  Women and men at least 18 years of age or older.

 -  Histologically confirmed invasive adenocarcinoma of the breast

 -  HER2 negative breast cancer as defined by ASCO-CAP criteria

 -  Tumor greater than or equal toT1, N0-3

 -  No evidence of distant metastasis

 -  Adequate bone marrow, hepatic, and renal function

 -  ECOG performance status 0 or 1

 Exclusion Criteria:

 -  Any other previous antitumor therapies for the current cancer event. Treatment for
 ductal carcinoma in situ (DCIS) is allowed; ie, surgery, hormonal therapy and
 radiation.

 -  Evidence of distant metastasis apparent prior to randomization

 -  Patients with inflammatory breast carcinoma

 -  Malignancy within the last 3 years, except: Stage 1 melanoma which does not require
 any further treatment after adequate surgical excision; adequately treated non
 melanoma skin cancer; Curatively treated in situ cancer of the cervix; Stage 1, Grade
 1 endometrial carcinoma; or Adequately treated contralateral breast carcinoma which
 has been disease free for a year; Other solid tumors including lymphomas (without bone
 marrow involvement) curatively treated with no evidence of disease for 5 years.

 -  Previous or concomitant systemic anti cancer therapies used for the treatment of
 cancer in the last 3 years.

 -  Prior treatment with a PARP inhibitor in any disease setting

 -  Concomitant use of Strong P gp inhibitors or inducers or BCRP inhibitors

 -  Patients who are unwilling or unable to use a highly effective method of contraception
 as outlined in this protocol

 -  Major surgery within 14 days prior to study entry

 -  Known history of cardiac disease, for example : Myocardial infarction or symptomatic
 cardiac ischemia within 24 weeks before screening; Congestive heart failure New York
 Heart Association Class III or IV; History of clinically significant ventricular
 arrhythmias within one year prior to randomization; History of Mobitz II second degree
 or third degree heart block, uncontrolled hypertension.

 -  Active clinically significant infection

 -  Clinically significant bleeding diathesis or coagulopathy

 -  Non healing wound, ulcer or bone fracture

 -  Known hypersensitivity to any of the components of talazoparib

 -  Patients with myelodysplastic syndrome/acute myeloid leukemia

 -  Patients with uncontrolled seizures.

 -  Any evidence of other disease or any concomitant medical or psychiatric problems which
 in the opinion of the Investigator would prevent completion of treatment