Clinical trial NCT01173497: A Study Evaluating INIPARIB in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Estrogen Receptor Negative (ER-Negative) Breast Cancer
Progesterone Receptor Negative (PR-Negative) Breast Cancer
Human Epidermal Growth Factor Receptor 2 Negative (HER2-Negative) Breast Cancer
Brain Metastases
Keywords: Triple negative breast cancer
Brain metastasis
BSI-201
iniparib
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: UNC Lineberger Comprehensive Cancer Center
First posted: 2010-08-02
Enrollment: 44
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy
timeFrame: 12 months
Secondary outcomes:
measure: Response Rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama At Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California At San Francisco
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Chapel Hill
country: United States
facility: University of North Carolina-CH Lineberger Comprehensive Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: