m-BEP: This phase I trial is assessing the safety and effect of combining ABT-199 with tamoxifen (a hormone therapy) in the treatment of oestrogen recepter positive breast cancerA Phase 1b Study of Bcl-2 inhibition with ABT-199 in combination with Tamoxifen in Metastatic ER-Positive Breast Cancer

Exclusion

1. Subjects who have previously been exposed to ABT-199
2. Absolute contraindication to tamoxifen use (e.g. life-threatening thromboembolic complications)
3. Subjects who are pregnant or lactating
4. Subjects with uncontrolled CNS metastases. Subjects who have had previous treatment of brain metastases with surgery or radiotherapy may be eligible if:
a) Treatment was administered > 4 weeks prior to study entry;
b) Subject is asymptomatic from CNS metastases; and
c) If subject is on steroid medication for the purpose of controlling CNS metastases, this must be stable (i.e. no change in dose for at least 2 weeks from the date of first dose of ABT-199).
5. Any anti-cancer therapy received within 21 days of the first dose of study drug including chemotherapy, radiotherapy or other investigational therapy. Exceptions: a) Bisphosphonate therapy or denosumab is allowed for subjects with bone metastases. b) Radiotherapy with palliative intent to non-target sites is allowed.
6. Subjects who are taking warfarin. The use of alternative anticoagulation therapy such as systemic low-molecular weight heparin should be discussed with the investigator.
7. Subjects who have had major surgery within 21 days of the first dose of study drug.
8. Subject has received the following agents within 7 days prior to the first dose of study drug:
a) Steroid therapy for anti-neoplastic intent;
b) CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin;
c) Potent CYP3A inducers such as rifampicin, carbamazepine, phenytoin and St. John’s Wort.
9. Subjects with active uncontrolled infection.
10. Known history of human immunodeficiency virus (HIV) infection, chronic Hepatitis B or C.
11. History of other malignancies within the past 5 years except for treated skin basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma less than or equal to 1.0 mm without ulceration, localised thyroid cancer, or cervical carcinoma in situ. Other malignancies considered to be at low risk of recurrence may also be included according to the discretion of the Chief Investigator.
12. Other history of medical or psychiatric condition that may interfere with the subject’s participation in the study.
13. Subjects with childbearing potential who refuse to use at least one of the following methods of contraception during and for a period of 30 days after study drug discontinuation:
a) Total abstinence from sexual intercourse as the preferred lifestyle of the subject; periodic abstinence is not acceptable;
b) Surgically sterile partner(s) e.g. vasectomy
c) Intrauterine device (IUD) or Mirena
d) Double-barrier method (contraceptive sponge, diaphragm or cervical cap with spermicidal jellies or cream AND a condom)
14. Subjects on contraception that is estrogen or progestin based (Mirena accepted)
15. Subjects who are on Hormone Replacement Therapy