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

Neoplasm Malignant Clinical Trial

Official title:

A Phase 1/1b Dose Escalation Study Evaluating Iniparib (BSI201/SAR240550) as a Single Agent and in Combination With Chemotherapeutic Regimens in Patients With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01455532
• Other study ID #: TED11746
• Secondary ID: U1111-1118-6091
• Status: Completed
• Phase: Phase 1
• First received: October 7, 2011
• Last updated: October 21, 2014
• Start date: November 2011
• Est. completion date: April 2014

Study information

• Verified date: October 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

The duration of the study for an individual patient will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (3 weeks or 4 weeks depending on regimen) of study treatment, and an end-of-treatment visit at least 30 days following the last administration of study drug. However, treatment may continue until precluded by toxicity, progression, or death.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: April 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• 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.

Exclusion criteria:

• 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.

• Not recovered to Grade =1 from adverse events (AE), per NCI-CTCAE Version 4.03 or to within 10% of pre-treatment baseline values, due to investigational drugs, radiation, or other medications administered more than 30 days before enrollment in this study. Alopecia at screening is not exclusionary.

• 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Malignant
• Neoplasms

Intervention

Drug:
• Iniparib (SAR240550-BSI-201)
Pharmaceutical form:Solution for infusion Route of administration: Intravenous
• Gemcitabine
Pharmaceutical form:Solution for infusion Route of administration: Intravenous
• Carboplatin
Pharmaceutical form:Solution for infusion Route of administration: Intravenous
• Placlitaxel
Pharmaceutical form:Solution for infusion Route of administration: Intravenous
• Pegylated liposomal doxorubicin
Pharmaceutical form:Solution for infusion Route of administration: Intravenous

Locations

Country	Name	City	State
United States	Investigational Site Number 840010	Augusta	Georgia
United States	Investigational Site Number 840001	Cincinnati	Ohio
United States	Investigational Site Number 840004	Los Angeles	California
United States	Investigational Site Number 840006	San Antonio	Texas
United States	Investigational Site Number 840002	Scottsdale	Arizona
United States	Investigational Site Number 840007	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of iniparib as single agent and in combination with chemotherapeutic agents related dose limiting toxicities (DLTs) observed at first cycle		3 - 4 weeks	Yes
Secondary	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	No
Secondary	Pharmakokinetic (PK) parameters: Cmax		0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose	No
Secondary	Pharmakokinetic (PK) parameters : tmax		0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose	No
Secondary	Pharmakokinetic (PK) parameters: tlast		0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose	No
Secondary	Pharmakokinetic (PK) parameters: AUC		0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose	No
Secondary	Pharmakokinetic (PK) parameters : t1/2z		0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose	No