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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain Metastases; 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
• Intervention / Treatment: Drug: INIPARIB + irinotecan

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • University of Alabama at Birmingham
  • California
    • San Francisco, California, United States
      • University of California at San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States
      • Georgetown University
  • Illinois
    • Chicago, Illinois, United States
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States
      • Indiana University Simon Cancer Center
  • Maryland
    • Baltimore, Maryland, United States
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States
      • University of Michigan
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • University of North Carolina-CH Lineberger Comprehensive Cancer Center
    • Durham, North Carolina, United States
      • Duke University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INIPARIB, irinotecan	Drug: INIPARIB + irinotecan; 21 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	AS measured by intra or extra cranial time to progression (TTP)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	as measured by RECIST	12 months

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: UNC Lineberger Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: July 28, 2010
• First Submitted That Met QC Criteria: July 29, 2010
• First Posted (Estimate): August 2, 2010

Study Record Updates

• Last Update Posted (Estimate): March 17, 2016
• Last Update Submitted That Met QC Criteria: February 17, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Triple negative breast cancer; Brain metastasis; BSI-201; iniparib
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Iniparib
• Other Study ID Numbers: TCD11608; 20100210 (Other Identifier: BiPar)