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

Sanofi

Status and phase

Completed

Phase 1

Conditions

Advanced Solid Tumors

Treatments

Drug: Ombrabulin (AVE8062)

Drug: Paclitaxel

Drug: Carboplatin

Study type

Interventional

Funder types

Industry

Identifiers

NCT01293630

TCD11270

U1111-1115-2568 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment

18 patients

Sex

All

Ages

20 to 75 years old

Volunteers

No Healthy Volunteers

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.