An early phase study of ABT-199 in combination with tamoxifen in metastatic ER-positive breast cancer

Phase 1

• Conditions: Metastatic breast cancer; Cancer

• Registration Number: ISRCTN98335443
• Lead Sponsor: Melbourne Health

Brief Summary

2019 Results article in https://pubmed.ncbi.nlm.nih.gov/30518523/ results (added 05/06/2020)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-03-16
• Last Update Posted: 9 January 2023
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 57

Inclusion Criteria

1. Subjects >18 years of age
2. Signed informed consent
3. Histological or cytological confirmation of metastatic carcinoma of the breast with the following tumour molecular characteristics:
3.1. ER positive (>1% positive stained carcinoma cells)
3.2. Bcl-2 positive (defined as >10% cells with at least moderate cytoplasmic staining; intensity 2-3 on 0-3 scale)
3.3. HER2 non-amplified
4. Subjects must nor have received tamoxifen within the last 3 months.
5. Subject must have evaluable or measurable disease (bone-only metastases are allowed).
6. Eastern Cooperative Oncology Group (ECOG) performance score of 1 or above.
7. Subjects of childbearing potential must have a negative serum pregnancy test.
8. Subject must have adequate organ and marrow function.
9. Life expectancy >6 months
10. Subjects must be suitable for oral drug administration.

Exclusion Criteria

1. Subjects who have previously been exposed to ABT-199
2. Absolute contraindication to tamoxifen use
3. Subjects who are pregnant or lactating
4. Subjects with uncontrolled CNS metastases
5. Any anti-cancer therapy received within 21 days of study treatment including chemotherapy, radiotherapy or other investigational therapy
6. Subjects who are taking warfarin
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:
8.1. Steroid therapy for anti-neoplastic intent
8.2. CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin
8.3. Potent CYP3A inducers such as rifampicin, carbamazepine, phenytoin and St John's Wort
9. Subjects with active uncontrolled infection
10. Known history of HIV infection, Hepatitis B or C
11. History of other malignancies within the past 5 years except for treated BCC, SCC, malignant melanoma <1mm, localised thyroid cancer or cervical carcinoma in situ
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 effective contraception during and for up to 30 days after study drug discontinuation
14. Subjects on contraception that is oestrogen or progestin based (Mirena accepted).
15. Subjects who are on hormone replacement therapy

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Maximum tolerated dose (MTD)<br> 2. Dose-limiting toxicities (DLTs)<br> Both reported within the first 4 weeks of treatment with the combination of ABT-199 and tamoxifen. This will be measured by assessing side-effects experienced by subjects during the first 4 weeks of treatment.<br>