A Dose Escalation Study of Iniparib as a Single Agent and in Combination in Solid Tumors

NCT01455532 | Completed Phase 1

• 2 other identifiers: TED11746U1111-1118-6091
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 6

Brief Summary

Primary Objective:

• To assess the safety and the maximum tolerated dose(MTD) of iniparib as a single agent and in combination with chemotherapeutic regimens in patients with advanced solid tumors that are refractory to standard therapy. Secondary Objectives:
• To assess the antitumor effect of iniparib (per Response Evaluation Criteria in Solid Tumors \[RECIST\]) Version 1.1 in patients with measurable disease.
• To characterize iniparib (and its metabolites, if possible) pharmacokinetics. Based on data generated by 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

Neoplasm Malignant

Outcome Measures

Primary Outcomes (1)

• Assessment of iniparib as single agent and in combination with chemotherapeutic agents related dose limiting toxicities (DLTs) observed at first cycle

  3 - 4 weeks

Secondary Outcomes (6)

• To assess the antitumor effect of iniparib according to the Response Evaluation Criteria in Solid Tumors [RECIST]) Version 1.1 in patients with measurable disease

  Up to 2 years

• Pharmakokinetic (PK) parameters: Cmax

  0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose

• Pharmakokinetic (PK) parameters : tmax

  0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose

• Pharmakokinetic (PK) parameters: tlast

  0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose

• Pharmakokinetic (PK) parameters: AUC

  0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose

Study Arms (4)

Iniparib, single agent

EXPERIMENTAL

Iniparib will be initially administered intravenously once weekly (days 1, 8, and 15) for 3 weeks, in a 21-day cycle. Then, iniparib will be administered twice weekly (days 1, 4, 8, 11, 15, and 18) in a 21-day cycle. Cycle1 (day 1 thru day 21) will be defined as the dose limiting toxicities (DLT) observation period. Starting dose is 15 mg/kg once weekly.

Drug: Iniparib (SAR240550-BSI-201)

Iniparib/Gemcitibine/Carboplatin

EXPERIMENTAL

Gemcitabine/carboplatin (GC) : Gemcitabine will be administered at 1,000 mg/m² as a 30min IV infusion and carboplatin area under the curve (AUC) 2 as a 60min IV infusion. Patients will receive gemcitabine/carboplatin infusions once weekly (days 1 and 8). Iniparib will be administered for two weeks, followed by a 1week of rest in a 21-day cycle (weekly schedule: days 1 and 8; twice weekly schedule: days: 1, 4, 8 and 11).

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

Iniparib/Paclitaxel

EXPERIMENTAL

Paclitaxel (P): Paclitaxel will be administered at the dose of 80 mg/m2 as a 60-minute intravenous infusion administered on days 1, 8, and 15 followed by a 1week of rest. Iniparib will be administered for three weeks, followed by 1week of rest in a 28-day cycle (weekly schedule: days 1, 8 and 15; twice weekly schedule: days 1, 4, 8, 11, 15 and 18).

Drug: Iniparib (SAR240550-BSI-201); Drug: Placlitaxel

Iniparib/Pegylated liposomal doxorubicin/Carboplatin

EXPERIMENTAL

Pegylated liposomal doxorubicin (Doxil)/Carboplatin (PLD) : Doxil will be administered at 30 mg/m² as a 30min IV infusion and carboplatin AUC 4 as a 60min IV infusion on day 1 every four weeks. Iniparib will be administered for two weeks in a 28-day cycle (weekly schedule: days 1, and 8; twice weekly schedule: days 1, 4, 8, and 11).

Drug: Iniparib (SAR240550-BSI-201); Drug: Carboplatin; Drug: Pegylated liposomal doxorubicin

Interventions

Iniparib (SAR240550-BSI-201) DRUG

Pharmaceutical form:Solution for infusion Route of administration: Intravenous

Iniparib, single agent; Iniparib/Gemcitibine/Carboplatin; Iniparib/Paclitaxel; Iniparib/Pegylated liposomal doxorubicin/Carboplatin

Gemcitabine DRUG

Pharmaceutical form:Solution for infusion Route of administration: Intravenous

Iniparib/Gemcitibine/Carboplatin

Carboplatin DRUG

Pharmaceutical form:Solution for infusion Route of administration: Intravenous

Iniparib/Gemcitibine/Carboplatin; Iniparib/Pegylated liposomal doxorubicin/Carboplatin

Placlitaxel DRUG

Pharmaceutical form:Solution for infusion Route of administration: Intravenous

Iniparib/Paclitaxel

Pegylated liposomal doxorubicin DRUG

Pharmaceutical form:Solution for infusion Route of administration: Intravenous

Iniparib/Pegylated liposomal doxorubicin/Carboplatin

Eligibility Criteria

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

You may qualify if:

• Capable of understanding and complying with the protocol requirements, and have signed the informed consent document
• ≥18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• To have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease; that is refractory to standard therapy and/or therapies known to provide clinical benefit or for which no standard therapy exists
• For phase 1b, patients for whom the backbone chemotherapy (dose and schedule) can be considered as a standard therapeutic regime for their cancer.
• Have measurable disease or non-measurable disease, defined according to RECIST Version 1.1. Patients with skin only metastases are eligible, if the appropriate photography documentation (including measurement) of the skin metastases is provided.
• Adequate organ and bone marrow function
• Willingness, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ an effective barrier method of contraception during the study drug administration and for a period of 6 months following the last dose.
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment, and at least 6 months after the last dose of study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. Sexually active men must agree to use a medically acceptable form of birth control during treatment and at least 6 months after the last dose. If a female partner becomes pregnant during course of study the treating physician should be informed immediately.

You may not qualify if:

• Systemic anticancer therapy within 14 days before the first dose of study drug.
• Known allergy or hypersensitivity to components of the iniparib, gemcitabine, paclitaxel, PLD,or carboplatin formulation.
• Prior radical (curative) radiation therapy for treatment of cancer ≥25% of the bone marrow (1). Prior radiation to the whole pelvis is not allowed. Prior radical radiotherapy must be completed at least 4 weeks before study entry.
• Patients who have received palliative radiation therapy for symptomatic metastases must have completed treatment ≥14 days prior to initiation of study treatment.
• Active brain metastases. Patients with treated brain metastases are eligible, if 1. Radiation therapy was completed at least 2 weeks prior to study treatment; 2. Follow-up scan shows no disease progression; and 3. Patient does not require steroids. Screening for brain metastases is not required if the patient is asymptomatic.
• Clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or IV), including pre-existing ventricular arrhythmia or conduction abnormality requiring medication, or cardiomyopathy or history of a myocardial infarction within the last 6 months
• Other major medical condition (eg, uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection) which the Investigator feels might compromise the patient's effective and safe participation in the trial.
• Pregnant or breastfeeding
• Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or Hepatitis C Antibodies (HCAb). Testing is not required unless circumstances warrant confirmation.
• Patients with acute or chronic leukemia or with any other disease likely to have a significant bone marrow infiltration (screening not required).
• Prior treatment with gemcitabine, carboplatin, paclitaxel, or Pegylated liposomal doxorubicin.
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (6)

Investigational Site Number 840002

Scottsdale, Arizona, 85258, United States

Location

Investigational Site Number 840004

Los Angeles, California, 90048, United States

Location

Investigational Site Number 840010

Augusta, Georgia, 30912, United States

Location

Investigational Site Number 840007

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840001

Cincinnati, Ohio, 45267-0542, United States

Location

Investigational Site Number 840006

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

iniparib; Gemcitabine; Carboplatin; liposomal doxorubicin

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: October 7, 2011
• First Posted: October 20, 2011
• Study Start: November 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: April 1, 2014
• Last Updated: October 22, 2014

Record last verified: 2014-10

Locations

US (6)