A Dose Escalation Study of Iniparib as a Single Agent and in Combination in Solid Tumors
- Conditions
- Neoplasm Malignant
- Interventions
- Registration Number
- NCT01455532
- Lead Sponsor
- Sanofi
- 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 59
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Iniparib, single agent Iniparib (SAR240550-BSI-201) 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. Iniparib/Gemcitibine/Carboplatin Iniparib (SAR240550-BSI-201) 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). Iniparib/Paclitaxel Iniparib (SAR240550-BSI-201) 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). Iniparib/Paclitaxel Placlitaxel 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). Iniparib/Pegylated liposomal doxorubicin/Carboplatin Carboplatin 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). Iniparib/Gemcitibine/Carboplatin Gemcitabine 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). Iniparib/Pegylated liposomal doxorubicin/Carboplatin Iniparib (SAR240550-BSI-201) 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). Iniparib/Pegylated liposomal doxorubicin/Carboplatin Pegylated liposomal doxorubicin 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). Iniparib/Gemcitibine/Carboplatin Carboplatin 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).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Pharmakokinetic (PK) parameters: Cmax 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 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 : tmax 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 Pharmakokinetic (PK) parameters : t1/2z 0, 0.5, 1, 1.33, 1.67, 2, 4, 5, 7 and 10 h post dose
Trial Locations
- Locations (6)
Investigational Site Number 840004
🇺🇸Los Angeles, California, United States
Investigational Site Number 840010
🇺🇸Augusta, Georgia, United States
Investigational Site Number 840007
🇺🇸St Louis, Missouri, United States
Investigational Site Number 840001
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840006
🇺🇸San Antonio, Texas, United States
Investigational Site Number 840002
🇺🇸Scottsdale, Arizona, United States