Dose Escalation, Safety and Pharmacokinetic Study of AVE8062 Combined With Cisplatin in Patients With Solid Tumors

June 10, 2011 updated by: Sanofi

An Open Label, Dose Escalation, Safety and Pharmacokinetics Phase 1 Study With Ombrabulin Administered as a 30-minute Intravenous Infusion in Combination With Cisplatin Administered as an Intravenous Infusion Every 3 Weeks in Patients With Advanced Solid Tumors

Primary Objective:

  • To determine the maximum tolerated dose based on the incidence of dose limiting toxicity and the maximum administered dose of ombrabulin in combination with cisplatin administered every 3 weeks in patients with advanced solid tumors.

Secondary Objectives:

  • To assess the overall safety profile of the combination therapy.
  • To characterize the pharmacokinetic profile of ombrabulin, its active metabolite RPR 258063, and cisplatin in combination.
  • To evaluate anti-tumor activity of the combination therapy.

Study Overview

Status

Completed

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 30 days after the last infusion of ombrabulin. The patient will continue treatment until disease progression, unacceptable toxicity, patient's refusal of further treatment.

Study Type

Interventional

Enrollment (Anticipated)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Tokyo, Japan
        • Sanofi-Aventis Administrative Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 :

  • Advanced solid tumor that has become refractory to conventional treatment or for which no standard therapy exists.

Exclusion criteria :

  • Eastern Cooperative Oncology Group performance status ≥ 2.
  • Concurrent treatment with any other anticancer therapy
  • Male or female patients who do not agree with contraception.
  • Washout period of less than 28 days from prior anticancer therapies (chemotherapy, targeted agents, immunotherapy and radiotherapy) or any investigational treatment, except for nitrosoureas, mitomycin which may not be used up to 42 days prior to the first cycle.No washout period is required for hormonal therapy that has to be discontinued before the first cycle.
  • Not recovered from all previous therapies (radiation, surgery, and medications). Adverse events related to previous therapies must be National Cancer Institute Common Terminology Criteria (NCI-CTCAE V3.0) grade≤1 (or alopecia≤grade 2) at screening or returned to the subject's baseline prior to their most recent previous therapy.
  • Symptomatic brain metastases and carcinomatous leptomeningitis.
  • Other serious illness or medical conditions not controlled by adequate treatment
  • Previous cumulative carboplatin dose higher than 3,000 mg/m2 or cisplatin higher than 600 mg/m2.
  • Patients whose disease has progressed or has recurred in less than 6 months from the completion of the previous platinum containing chemotherapy
  • Known platinum compound hypersensitivity.
  • Neuropathy and ototoxicity due to previous platinum chemotherapy.
  • Inadequate organ function
  • Documented medical history of myocardial infarction, documented angina pectoris, arrhythmia especially severe conduction disorder such as second or third degree atrio-ventricular block, stroke, or history of arterial or venous thrombo-embolism within the past 180 days requiring anticoagulants.
  • Patient with a left ventricular ejection fraction<50% by echocardiography.
  • Patients with a baseline QTc interval>0.45, or family history of Long QT Syndrome.
  • Patient with uncontrolled hypertension and patient with organ damage related to hypertension such as left ventricular hypertrophy or grade 2 ocular fundscopic changes or kidney impairment.
  • Patients with growing vessel disease (eg age-related macular degeneration, diabetic retinopathy, rheumatoid arthritis), or ongoing wound healing process. Patients should be enrolled in the study at least 28 days after surgery
  • 12-lead Electrocardiogram: ST- and T-wave changes suggesting ischemia
  • Hypertension defined as systolic blood pressure (BP)>140 mmHg or diastolic BP>90 mmHg on two repeated measurements at 30 minutes intervals.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ombrabulin/cisplatin
AVE8062 combined with 75 mg/m2 of cisplatin will be administered once in every 3 weeks, with 30-minute intravenous infusion

Pharmaceutical form:injection solution

Route of administration: intravenous infusion

Pharmaceutical form: injection solution

Route of administration: intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose limiting toxicity
Time Frame: 3 weeks (cycle 1)
3 weeks (cycle 1)

Secondary Outcome Measures

Outcome Measure
Time Frame
Global safety profile based on treatment emergent adverse events, serious adverse events, and laboratory abnormalities
Time Frame: on-treatment period + 30 days
on-treatment period + 30 days
Pharmacokinetic parameters of AVE8062
Time Frame: Cycle 1 : Day 1 and 2; up to Cycle 4 : Day 1
Cycle 1 : Day 1 and 2; up to Cycle 4 : Day 1
Pharmacokinetic parameters of cisplatin
Time Frame: Day 1 to 4 of Cycle 1
Day 1 to 4 of Cycle 1
Pharmacokinetic parameters of AVE8062's active metabolite RPR258063
Time Frame: Cycle 1 : Day 1 and 2; up to Cycle 4 : Day 1
Cycle 1 : Day 1 and 2; up to Cycle 4 : Day 1
Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Time Frame: up to a maximum of 11 months
up to a maximum of 11 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (ACTUAL)

May 1, 2011

Study Completion (ACTUAL)

May 1, 2011

Study Registration Dates

First Submitted

November 24, 2009

First Submitted That Met QC Criteria

November 25, 2009

First Posted (ESTIMATE)

November 26, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

June 13, 2011

Last Update Submitted That Met QC Criteria

June 10, 2011

Last Verified

June 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TCD11088

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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