A Study Evaluating INIPARIB in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis

Brain Metastases Clinical Trial

Official title:

A Phase II Study of the PARP Inhibitor, INIPARIB (BSI-201), in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01173497
• Other study ID #: TCD11608
• Secondary ID: 20100210
• Status: Completed
• Phase: Phase 2
• First received: July 28, 2010
• Last updated: February 17, 2016
• Start date: July 2010
• Est. completion date: July 2013

Study information

• Verified date: February 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: July 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Breast Neoplasms
• Estrogen Receptor Negative (ER-Negative) Breast Cancer
• Human Epidermal Growth Factor Receptor 2 Negative (HER2-Negative) Breast Cancer
• Neoplasm Metastasis
• Progesterone Receptor Negative (PR-Negative) Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• INIPARIB + irinotecan
21 day cycle

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama At Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of North Carolina-CH Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	Duke University	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Vanderbilt University	Nashville	Tennessee
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of California At San Francisco	San Francisco	California
United States	Georgetown University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	UNC Lineberger Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy	AS measured by intra or extra cranial time to progression (TTP)	12 months	No
Secondary	Response Rate	as measured by RECIST	12 months	No