NCT00540358

Brief Summary

The purpose of this clinical trial was to determine whether combining iniparib (BSI-201) with standard chemotherapy in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer patients improve clinical benefit compared to treatment with standard chemotherapy alone. Based on data generated by BiPar/Sanofi, it was concluded that iniparib does not possess characteristics typical of the poly (ADP-ribose) polymerase (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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
123

participants targeted

Target at P75+ for phase_2 breast-cancer

Timeline
Completed

Started Oct 2007

Geographic Reach
1 country

18 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2007

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

October 4, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 8, 2007

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2009

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2010

Completed
Last Updated

December 28, 2012

Status Verified

December 1, 2012

Enrollment Period

2.1 years

First QC Date

October 4, 2007

Last Update Submit

December 21, 2012

Conditions

Keywords

Triple negative breast cancer

Outcome Measures

Primary Outcomes (1)

  • Clinical benefit rate

    Clinical benefit rate was defined as the percentage of patients with complete response, partial response or stable disease ≥6 months.

    until cut-off date established so that all patients were evaluable for primary outcome measure

Secondary Outcomes (2)

  • Objective response rate

    until cut-off date established so that all patients were evaluable for primary outcome measure

  • Progression-free survival

    until cut-off date established so that all patients were evaluable for primary outcome measure

Study Arms (2)

Arm G/C

ACTIVE COMPARATOR

Standard chemotherapy with gemcitabine/carboplatin on Days 1 and 8 of 21-day cycle(s)

Drug: gemcitabine/carboplatin

Arm G/C/I

EXPERIMENTAL

Standard chemotherapy with gemcitabine/carboplatin on Days 1 and 8, plus iniparib on Days 1, 4, 8, and 11 of 21-day cycle(s)

Drug: gemcitabine/carboplatinDrug: iniparib

Interventions

Gemcitabine and carboplatin administered according to instructions in the package inserts.

Arm G/CArm G/C/I

Body weight adjusted dose 1 hour intravenous infusion

Also known as: BSI-201, SAR240550
Arm G/C/I

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • At least 18 years of age;
  • Metastatic breast cancer (Stage IV) with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria;
  • prior chemotherapy regimens in the metastatic setting;
  • Histologically documented (either primary or metastatic site) breast cancer that was ER-negative, PR-negative, and HER-2 nonoverexpressing by immunohistochemistry (0,1) or non-gene amplification by fluorescence in situ hybridization (FISH);
  • Completion of prior chemotherapy at least 2 weeks prior to trial entry and recovery from toxicity of prior chemotherapy;
  • Radiation therapy must have been completed at least 2 weeks prior to trial entry, and radiated lesions may not have served as measurable disease;
  • Patient may have had central nervous system (CNS) metastases if he/she did not require steroids, whole brain radiation therapy (XRT), gamma/cyber knife, and brain metastases were clinically stable without symptomatic progression;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
  • Adequate organ function defined as: absolute neutrophil count (ANC)≥1,500/mm3, platelets ≥100,000/mm3, creatinine clearance \>50mL/min, ALT and AST \<2.5 x upper limit of normal (ULN) (or \<5 x ULN in case of liver metastases); total bilirubin \<1.5 mg/dL.
  • Tissue block (primary or metastatic) available for PARP and PG studies was recommended, although its absence did not exclude subjects from participating;
  • Woman of child bearing potential must have had documented negative pregnancy test within two weeks of trial entry and agreed to acceptable birth control during the duration of the trial therapy;
  • Signed, IRB approved written informed consent.

You may not qualify if:

  • Lesions identifiable only by positron emission tomography (PET);
  • Prior treatment with gemcitabine, carboplatin, cisplatin or iniparib;
  • Major medical conditions that might have affected trial participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection);
  • Significant history of uncontrolled cardiac disease; i.e. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy that was either symptomatic or asymptomatic but with decreased ejection fraction \<45%;
  • Other significant comorbid condition which the investigator felt might compromise effective and safe participation in the trial;
  • Patient enrolled in another investigational device or drug trial, or was receiving other investigational agents;
  • Concurrent or prior (within 7 days of trial day 1) anticoagulation therapy (low dose for port maintenance allowed);
  • Concurrent radiation therapy was not permitted throughout the course of the trial;
  • Inability to comply with the requirements of the trial;
  • Pregnant or lactating woman;
  • Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Research Site

Birmingham, Alabama, United States

Location

Research Site

Denver, Colorado, United States

Location

Research Site

Torrington, Connecticut, United States

Location

Research Site

Ocoee, Florida, United States

Location

Research Site

Indianapolis, Indiana, United States

Location

Research Site

Overland Park, Kansas, United States

Location

Research Site

Henderson, Nevada, United States

Location

Research Site

Hooksett, New Hampshire, United States

Location

Research Site

Raleigh, North Carolina, United States

Location

Research Site

Bedford, Texas, United States

Location

Research Site

Dallas, Texas, United States

Location

Research Site

El Paso, Texas, United States

Location

Research Site

Fort Worth, Texas, United States

Location

Research Site

Houston, Texas, United States

Location

Research Site

Tyler, Texas, United States

Location

Research Site

Fairfax, Virginia, United States

Location

Research Site

Vancouver, Washington, United States

Location

Research Site

Yakima, Washington, United States

Location

Related Publications (1)

  • O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011 Jan 20;364(3):205-14. doi: 10.1056/NEJMoa1011418. Epub 2011 Jan 5.

MeSH Terms

Conditions

Breast NeoplasmsTriple Negative Breast Neoplasms

Interventions

GemcitabineCarboplatininiparib

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingCoordination ComplexesOrganic Chemicals

Study Officials

  • Clinical Sciences & Operations

    Sanofi

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

October 4, 2007

First Posted

October 8, 2007

Study Start

October 1, 2007

Primary Completion

November 1, 2009

Study Completion

June 1, 2010

Last Updated

December 28, 2012

Record last verified: 2012-12

Locations