Clinical trial NCT01293630: A Dose-escalation Study of Ombrabulin in Combination With Paclitaxel and Carboplatin in Patients With Advanced Solid Tumors
Official title: An Open-label, Dose-escalation, Safety and Pharmacokinetics Phase I Study of Ombrabulin in Combination With Paclitaxel and Carboplatin Every 3 Weeks in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-02-10
Enrollment: 18
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to determine the maximum tolerated dose (MTD) based on the incidence of dose limiting toxicity (DLT) and the maximum administered dose (MAD) of ombrabulin combined with paclitaxel and carboplatin administered every 3 weeks in patients with advanced solid tumors.

Secondary Objectives:

* To assess the overall safety profiles of the combination therapy
* To characterize the pharmacokinetic profile of ombrabulin, its active metabolite RPR 258063, paclitaxel, and carboplatin when used in combination
* To document the objective tumor response

Detailed description: The duration of the study for each patient will include an up to 4-week screening phase, 21-day study treatment cycles, an end of treatment visit and a follow-up period.

Eligibility criteria: Inclusion criteria:

* Patients with advanced solid tumor for which the combination paclitaxel and carboplatin is potentially effective such as lung cancer, epithelial ovarian cancer.
* Patients who have signed and dated an Institutional Review Board (IRB)-approved patient informed consent form prior to study enrollment or performance of any study-specific procedures.

Exclusion criteria:

* Less than 20 or above 75 years of age ECOG performance status ≥2.
* Patients with more than 1 line of previous chemotherapy for advanced or metastatic disease (adjuvant/neoadjuvant and targeted agents \[eg gefitinib\] excluded)
* Concurrent treatment with any other anticancer therapy (except palliative radiotherapy),
* Women of childbearing potential who does not agree with contraception.
* Washout period of less than 28 days from prior anticancer therapies
* Symptomatic brain metastases and carcinomatous leptomeningitis.
* Other serious illness or medical conditions
* Current peripheral neuropathy ≥grade 2 and ototoxicity,
* Absolute neutrophils counts\<1.5 x 10E9/L. - Platelets count\<100 x 10E9/L. - hemoglobin \<9.0 g/dL (without red blood cell transfusion within 28 days before the test). - Creatinine Clearance\<55 mL/min. - Total bilirubin \>upper normal limits of the institutional norms. - ALT/AST \>1.5 times the upper normal limits of the institutional norms. - AP\>2.5 times the upper normal limits of the institutional norms.
* Medical history of myocardial infarction, angina pectoris, congestive heart failure, coronary artery bypass graft , arrhythmia , stroke or history of arterial or venous thrombo-embolism within the past 180 days requiring anticoagulants.
* Patient with a LVEF \<50% by echocardiography.
* Patient with uncontrolled hypertension and patient with organ damage related to hypertension such as left ventricular hypertrophy or grade 2 ocular fundoscopic changes or kidney impairment.
* Hypertension defined as systolic BP \>140 mmHg or diastolic BP \>90 mmHg on two repeated measurements at 30 minutes interval.

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

Primary outcomes:
measure: The number of of drug related adverse events meeting the defined dose limiting toxicity at Cycle 1
timeFrame: 3 weeks
Secondary outcomes:
measure: The number of treatment emergent adverse events
timeFrame: 30 days after the last injection
measure: The number of serious adverse events
timeFrame: 30 days after the last injection
measure: The number of laboratory abnormalities
timeFrame: 30 days after the last injection
measure: Pharmacokinetic parameter of ombrabulin: Cmax
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of RPR258063: tmax
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of paclitaxel: Cmax
timeFrame: Day 1-3 at Cycle 1
measure: Pharmacokinetic parameter of carboplatin (free and total platinum): Cmax
timeFrame: Day 1-3 at Cycle 1
measure: Investigator determination of response
timeFrame: 30 days after the last injection
measure: Pharmacokinetic parameter of ombrabulin: AUC
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of ombrabulin: CL
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of ombrabulin: Vss
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of ombrabulin: t 1/2
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of RPR258063: Cmax
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of RPR258063: AUC
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of RPR258063: t 1/2
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of RPR258063: Metabolic Ratio
timeFrame: Day 1-2 at Cycle 1
measure: Pharmacokinetic parameter of paclitaxel: AUC
timeFrame: Day 1-3 at Cycle 1
measure: Pharmacokinetic parameter of paclitaxel: CL
timeFrame: Day 1-3 at Cycle 1
measure: Pharmacokinetic parameter of paclitaxel: Vss
timeFrame: Day 1-3 at Cycle 1
measure: Pharmacokinetic parameter of paclitaxel: t 1/2
timeFrame: Day 1-3 at Cycle 1
measure: Pharmacokinetic parameter of carboplatin (free and total platinum): AUC
timeFrame: Day 1-3 at Cycle 1
measure: Pharmacokinetic parameter of carboplatin (free and total platinum): CL
timeFrame: Day 1-3 at Cycle 1
measure: Pharmacokinetic parameter of carboplatin (free and total platinum): Vss
timeFrame: Day 1-3 at Cycle 1
measure: Pharmacokinetic parameter of carboplatin (free and total platinum): t 1/2
timeFrame: Day 1-3 at Cycle 1
Other outcomes:
Locations:
city: Akashi-Shi
country: Japan
facility: Investigational Site Number 392002
city: Hidaka-Shi
country: Japan
facility: Investigational Site Number 392001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: