talazoparib for neoadjuvant treatment of germline brca1/2 mutation patients with early human epidermal growth factor receptor 2 negative breast cancer

Conditions: Early Breast Cancer

Summary: 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.

Eligibility criteria:
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

Keywords: neoadjuvant therapy, human epidermal growth factor receptor 2 negative breast cancer, brca positive