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

Purpose

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

Condition	Intervention	Phase
Advanced Solid Tumors	Drug: Ombrabulin (AVE8062) Drug: Paclitaxel Drug: Carboplatin	Phase 1

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Paclitaxel Carboplatin

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

The number of of drug related adverse events meeting the defined dose limiting toxicity at Cycle 1 [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The number of treatment emergent adverse events [ Time Frame: 30 days after the last injection ] [ Designated as safety issue: Yes ]
The number of serious adverse events [ Time Frame: 30 days after the last injection ] [ Designated as safety issue: Yes ]
The number of laboratory abnormalities [ Time Frame: 30 days after the last injection ] [ Designated as safety issue: Yes ]
Pharmacokinetic parameter of ombrabulin: Cmax [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of RPR258063: tmax [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of paclitaxel: Cmax [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of carboplatin (free and total platinum): Cmax [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Investigator determination of response [ Time Frame: 30 days after the last injection ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of ombrabulin: AUC [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of ombrabulin: CL [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of ombrabulin: Vss [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of ombrabulin: t 1/2 [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of RPR258063: Cmax [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of RPR258063: AUC [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of RPR258063: t 1/2 [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of RPR258063: Metabolic Ratio [ Time Frame: Day 1-2 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of paclitaxel: AUC [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of paclitaxel: CL [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of paclitaxel: Vss [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of paclitaxel: t 1/2 [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of carboplatin (free and total platinum): AUC [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of carboplatin (free and total platinum): CL [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of carboplatin (free and total platinum): Vss [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]
Pharmacokinetic parameter of carboplatin (free and total platinum): t 1/2 [ Time Frame: Day 1-3 at Cycle 1 ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	December 2010
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Ages Eligible for Study:	20 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01293630

Locations

Japan
Investigational Site Number 392002
Akashi-Shi, Japan, 673-8558
Investigational Site Number 392001
Hidaka-Shi, Japan, 350-1241

Sponsors and Collaborators

Sanofi

Investigators

Study Director:

Clinical Sciences & Operations

Sanofi

More Information

No publications provided

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT01293630 History of Changes
Other Study ID Numbers:	TCD11270, U1111-1115-2568
Study First Received:	February 8, 2011
Last Updated:	April 3, 2013
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:

Neoplasms
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 22, 2013