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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01213381
First received: September 30, 2010
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Advance Solid Tumors
Drug: Iniparib (SAR240550 - BSI-201)
Drug: Gemcitabine
Drug: Carboplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Evaluating the Safety and Pharmacokinetics of SAR240550 Administered Twice Weekly in Patients With Advanced Solid Tumors.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Dose Limiting Toxicity in cycle 1 [ Time Frame: 3 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy assessment as tumor response defined by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 30 days after the last injection ] [ Designated as safety issue: No ]
  • Safety based on clinical and laboratory tests and Adverse Events (AEs) [ Time Frame: 30 days after the last injection ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of SAR240550 [ Time Frame: Cycle 1 and Cycle 2 ] [ Designated as safety issue: No ]
  • Pharmacodynamics of SAR240550 [ Time Frame: Cycle1, Cycle 2 and 30 days after the last injection ] [ Designated as safety issue: No ]
  • Pharmacogenomic analysis of glutathione S-transferase (GST) genotypes [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: September 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR240550
  • single cohort: SAR240550
  • combination cohort: SAR240550 in combination with Gemcitabine and Carboplatin
Drug: Iniparib (SAR240550 - BSI-201)

Pharmaceutical form:sterile aqueous solution

Route of administration: intravenous

Drug: Gemcitabine

Pharmaceutical form:sterile aqueous solution

Route of administration: intravenous

Drug: Carboplatin

Pharmaceutical form:sterile aqueous solution

Route of administration: intravenous


Detailed Description:

The duration of the study for each patient will include an up to 4-week screening phase, 21-day study cycle(s), followed by a 30 day follow-up.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

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

Exclusion criteria:

  • 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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01213381

Locations
Japan
Sanofi-Aventis Investigational Site Number 392001
Kobe-Shi, Japan
Sanofi-Aventis Investigational Site Number 392002
Matsuyama-Shi, Japan
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01213381     History of Changes
Other Study ID Numbers: TED11451, U1111-1117-3152
Study First Received: September 30, 2010
Last Updated: May 23, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Neoplasms
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 21, 2014