NCT00687765

Brief Summary

The phase I portion of study is designed to determine the Maximum Tolerated Dose (MTD) of BSI-201 with two clinically relevant dosing regimens of temozolomide (TMZ). Secondary objectives in the phase I trial include determining the PK of BSI-201 in malignant glioma patients and correlating BSI-201 PK with degree of PARP-1 inhibition. A safety run-in will confirm the safety of BSI-201 added to standard TMZ and radiation therapy and the phase II portion of the study will assess the efficacy and tolerability of the MTD dose of BSI-201 with daily TMZ and radiation therapy followed by adjuvant TMZ in patients with newly diagnosed GBM and assess overall survival as the primary outcome measure. Information on each phase of the study will be listed when each phase opens for enrollment. 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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
126

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jul 2008

Longer than P75 for phase_1

Geographic Reach
1 country

8 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

First Submitted

Initial submission to the registry

May 28, 2008

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 2, 2008

Completed
29 days until next milestone

Study Start

First participant enrolled

July 1, 2008

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2015

Completed
Last Updated

September 14, 2022

Status Verified

July 1, 2015

Enrollment Period

6.9 years

First QC Date

May 28, 2008

Last Update Submit

September 8, 2022

Conditions

Glioblastoma

Keywords

patients with newly diagnosed glioblastoma

Outcome Measures

Primary Outcomes (1)

  • To determine the Maximum Tolerated Dose (MTD) of BSI-201, administered as an IV infusion in patients with newly diagnosed malignant glioma when given with temozolomide (TMZ) after the completion of standard radiation therapy and concomitant TMZ

    10 weeks

Study Arms (1)

1

EXPERIMENTAL
Drug: bsi-201 plus temozolomide

Interventions

bsi-201 plus temozolomideDRUG

BSI-201 given iv. 2x weekly, temozolomide given orally

1

Eligibility Criteria

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

You may qualify if:

  • Patients must be at least 18 years of age
  • Patients must have a Karnofsky performance status \> 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • Patients must have the following hematologic, renal and liver function (i.e. Absolute neutrophil count \> 1500/mm3, Platelets \> 100,000/mm3, creatinine \< 1.7 mg/dl, total bilirubin ≤ 1.5 mg/dl, transaminases \< 4 times above the upper limits of the institutional normal
  • Patients must be able to provide written informed consent
  • Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug as well as the standard drug (temozolomide) may be harmful to the developing fetus or nursing infant
  • Patients must have a Mini Mental Status Exam score of \> 15
  • Patients must have tumor tissue form completed and signed by a pathologist. See section 9.6 for details
  • Phase I Criteria (Phase I Patients ONLY)
  • Patients must have histologically proven supratentorial malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or glioblastoma multiforme)
  • Patients must have received at least 80% of planned temozolomide and radiation therapy with no grade 3 or grade 4 toxicity attributed to the temozolomide
  • Patients must have received planned treatment with radiation therapy and concomitant temozolomide at least 28 days but no more than 49 days prior to starting treatment on this study
  • Patients must have Gadolinium MRI or contrast CT scan within 28 days of starting treatment

You may not qualify if:

  • Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
  • Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug and temozolomide may be harmful to the developing fetus or nursing infant
  • Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents)
  • Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for greater than five years are eligible for this study
  • Patients cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) and must not have taken them for at least 10 days
  • Phase I Ineligibility Criteria (Phase I Patients ONLY)
  • Patients who have had repeat craniotomy for tumor therapy after receiving RT and TMZ treatment
  • Patients who received other chemotherapeutics or investigational agents in addition to their radiation therapy and concomitant temozolomide treatment. Patients who have received Gliadel wafers are eligible for this study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Research Site

Birmingham, Alabama, 35294, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Baltimore, Maryland, United States

Location

Research Site

Boston, Massachusetts, 92114, United States

Location

Research Site

Detroit, Michigan, 48202, United States

Location

Research Site

Winston-Salem, North Carolina, 27157, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

iniparibTemozolomide

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

DacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Clinical Sciences & Operations

    Sanofi

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

May 28, 2008

First Posted

June 2, 2008

Study Start

July 1, 2008

Primary Completion

June 1, 2015

Study Completion

June 1, 2015

Last Updated

September 14, 2022

Record last verified: 2015-07

Locations

US(8)