Safety and Pharmacokinetics of SAR240550 (BSI-201) Twice Weekly in Patients With Advanced Solid Tumors

NCT01213381 | Completed Phase 1

• 2 other identifiers: TED11451U1111-1117-3152
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objective: \- To determine a dose of SAR240550 to be further studied in combination with chemotherapy regimens Secondary Objectives:

• To determine the dose limiting toxicity (DLT) of SAR240550 and SAR240550 in combination with chemotherapy regimen (gemcitabine and carboplatin
• To assess safety profiles: significant laboratory changes and adverse events (AEs)
• To make a preliminary assessment of antitumor effect in study subjects per Response Evaluation Criteria in Solid Tumors (RECIST) with measurable disease
• To characterize SAR240550 and metabolites, 4-iodo-3-amino benzamide (IABM) and 4-iodo-3-amino-benzoic acid (IABA), pharmacokinetics
• To collect blood samples for glutathione S-transferase (GST) genotypes at baseline) 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.

Conditions

Advance Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity in cycle 1

  3 Weeks

Secondary Outcomes (5)

• Efficacy assessment as tumor response defined by Response Evaluation Criteria in Solid Tumors (RECIST)

  30 days after the last injection

• Safety based on clinical and laboratory tests and Adverse Events (AEs)

  30 days after the last injection

• Pharmacokinetics of SAR240550

  Cycle 1 and Cycle 2

• Pharmacodynamics of SAR240550

  Cycle1, Cycle 2 and 30 days after the last injection

• Pharmacogenomic analysis of glutathione S-transferase (GST) genotypes

  Cycle 1

Study Arms (1)

SAR240550

EXPERIMENTAL

* single cohort: SAR240550 * combination cohort: SAR240550 in combination with Gemcitabine and Carboplatin

Drug: Iniparib (SAR240550 - BSI-201); Drug: Gemcitabine; Drug: Carboplatin

Interventions

Iniparib (SAR240550 - BSI-201) DRUG

Pharmaceutical form:sterile aqueous solution Route of administration: intravenous

SAR240550

Gemcitabine DRUG

Pharmaceutical form:sterile aqueous solution Route of administration: intravenous

SAR240550

Carboplatin DRUG

Pharmaceutical form:sterile aqueous solution Route of administration: intravenous

SAR240550

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Histologically or cytologically documented advanced solid tumor that was refractory to standard therapy or for which no standard therapy is available

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of ≥2
• Known hematological malignancies
• Symptomatic or untreated brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and corticosteroids
• Myocardial infarction within 6 months of study Day 1, unstable angina, congestive heart failure with New York Heart Association \>class II, uncontrolled hypertension
• Active human immunodeficiency virus infection, hepatitis C virus, or chronic hepatitis B infection
• Major surgery within 28 days of study Day 1
• Not recovered from all previous therapies (i.e. radiation, surgery, and medications)
• Adverse events related to previous therapies must be Common Terminology Criteria for Adverse Events (CTCAE) grade ≤ 1 (except alopecia) at screening or returned to the subject's baseline prior to their most recent previous therapy
• Inadequate organ and bone marrow function Radiation therapy within 14 days of study Day 1
• Chemotherapy or antibody therapy for treatment of underlying malignancy within 21 days of study Day 1
• Concurrent or prior (within 7 days of study Day 1) anticoagulation therapy
• Currently enrolled or was enrolled within 30 days of completing other investigational drug study, or receiving other investigational agent not approved for any indications
• Subject who had been previously enrolled in this study . Not available for follow-up assessment
• Any kind of disorder that compromised the ability of the subject to give written informed consent and/or comply with the study procedures
• Patient who is judged by the investigator as not suitable for participation in the study

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

Sanofi-Aventis Investigational Site Number 392001

Kobe, Japan

Location

Sanofi-Aventis Investigational Site Number 392002

Matsuyama, Japan

Location

MeSH Terms

Interventions

iniparib; Gemcitabine; Carboplatin

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2010
• First Posted: October 4, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: May 24, 2013

Record last verified: 2013-05

Locations

JP (2)