A Dose-escalation Study of Ombrabulin in Combination With Paclitaxel and Carboplatin in Patients With Advanced Solid Tumors

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

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

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Ombrabulin (AVE8062); Drug: Paclitaxel; Drug: Carboplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Akashi-Shi, Japan
    • Investigational Site Number 392002
  • Hidaka-Shi, Japan
    • Investigational Site Number 392001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort - 1 through 5; AVE8062 combined with paclitaxel and carboplatin will be administered once every 3 weeks	Drug: Ombrabulin (AVE8062); Pharmaceutical form:solution Route of administration: intravenous; Drug: Paclitaxel; Pharmaceutical form:solution Route of administration: intravenous; Drug: Carboplatin; Pharmaceutical form:solution Route of administration: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of of drug related adverse events meeting the defined dose limiting toxicity at Cycle 1	3 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The number of treatment emergent adverse events	30 days after the last injection
The number of serious adverse events	30 days after the last injection
The number of laboratory abnormalities	30 days after the last injection
Pharmacokinetic parameter of ombrabulin: Cmax	Day 1-2 at Cycle 1
Pharmacokinetic parameter of RPR258063: tmax	Day 1-2 at Cycle 1
Pharmacokinetic parameter of paclitaxel: Cmax	Day 1-3 at Cycle 1
Pharmacokinetic parameter of carboplatin (free and total platinum): Cmax	Day 1-3 at Cycle 1
Investigator determination of response	30 days after the last injection
Pharmacokinetic parameter of ombrabulin: AUC	Day 1-2 at Cycle 1
Pharmacokinetic parameter of ombrabulin: CL	Day 1-2 at Cycle 1
Pharmacokinetic parameter of ombrabulin: Vss	Day 1-2 at Cycle 1
Pharmacokinetic parameter of ombrabulin: t 1/2	Day 1-2 at Cycle 1
Pharmacokinetic parameter of RPR258063: Cmax	Day 1-2 at Cycle 1
Pharmacokinetic parameter of RPR258063: AUC	Day 1-2 at Cycle 1
Pharmacokinetic parameter of RPR258063: t 1/2	Day 1-2 at Cycle 1
Pharmacokinetic parameter of RPR258063: Metabolic Ratio	Day 1-2 at Cycle 1
Pharmacokinetic parameter of paclitaxel: AUC	Day 1-3 at Cycle 1
Pharmacokinetic parameter of paclitaxel: CL	Day 1-3 at Cycle 1
Pharmacokinetic parameter of paclitaxel: Vss	Day 1-3 at Cycle 1
Pharmacokinetic parameter of paclitaxel: t 1/2	Day 1-3 at Cycle 1
Pharmacokinetic parameter of carboplatin (free and total platinum): AUC	Day 1-3 at Cycle 1
Pharmacokinetic parameter of carboplatin (free and total platinum): CL	Day 1-3 at Cycle 1
Pharmacokinetic parameter of carboplatin (free and total platinum): Vss	Day 1-3 at Cycle 1
Pharmacokinetic parameter of carboplatin (free and total platinum): t 1/2	Day 1-3 at Cycle 1

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: February 8, 2011
• First Submitted That Met QC Criteria: February 9, 2011
• First Posted (Estimate): February 10, 2011

Study Record Updates

• Last Update Posted (Estimate): October 30, 2015
• Last Update Submitted That Met QC Criteria: October 29, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: TCD11270; U1111-1115-2568 (Other Identifier: UTN)