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

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.

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.