Brain Metastases, Estrogen Receptor Negative (ER-Negative) Breast Cancer, Human Epidermal Growth Factor Receptor 2 Negative (HER2-Negative) Breast Cancer, Progesterone Receptor Negative (PR-Negative) Breast Cancer
Conditions
Keywords
Triple negative breast cancer, Brain metastasis, BSI-201, iniparib
Brief summary
The purpose of the study is to investigate the response rate for triple negative breast cancer patients with brain metastasis when INIPARIB is used in combination with irinotecan. Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.
Interventions
DRUGINIPARIB + irinotecan
21 day cycle
Sponsors
UNC Lineberger Comprehensive Cancer Center
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- 1. Histologically-confirmed, ER negative, PR negative and Her2 negative adenocarcinoma of the breast with brain lesion on radiographic imaging. 2. ECOG Performance Status of 0-2. 3. Life expectancy of \>12 weeks. 4. No limit to prior therapies with last anti-cancer treatment ≥ 2 weeks from initiation of protocol-based therapy provided all toxicities (other than alopecia) have resolved to ≤Grade 1 or baseline. 5. No active serious infection or other comorbid illness which would impair ability to participate in the trial. 6. Stable or decreasing dose of steroids for ≥ 7 days. 7. Interval ≥ 4 weeks between open brain biopsy and initiation of protocol-based therapy. 8. Patients must have adequate organ function.
Exclusion criteria
- 1. Pregnant or breast-feeding 2. Prior allergic reaction to INIPARIB 3. Prior allergic reaction to irinotecan. 4. Evidence of hemorrhage or impending herniation on baseline brain imaging 5. Evidence of diffuse leptomeningeal disease on brain MRI or by previously documented CSF cytology-NOTE: discrete dural metastases are permitted. 6. Clinically significant cardiac, renal, hepatic, infectious or pulmonary disease which might affect trial participation. 7. Concurrent or planned radiation, hormonal, chemotherapeutic, experimental or targeted biologic therapy. 8. Contraindication to gadolinium-enhanced MRI imaging. 9. Inability to comply with study and/or follow-up procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy | 12 months | AS measured by intra or extra cranial time to progression (TTP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 12 months | as measured by RECIST |
Countries
United States
Outcome results
None listed