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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01293630
• Other study ID #: TCD11270
• Secondary ID: U1111-1115-2568
• Status: Completed
• Phase: Phase 1
• First received: February 8, 2011
• Last updated: October 29, 2015
• Start date: January 2011
• Est. completion date: October 2013

Study information

• Verified date: October 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• Ombrabulin (AVE8062)
Pharmaceutical form:solution Route of administration: intravenous
• Paclitaxel
Pharmaceutical form:solution Route of administration: intravenous
• Carboplatin
Pharmaceutical form:solution Route of administration: intravenous

Locations

Country	Name	City	State
Japan	Investigational Site Number 392002	Akashi-Shi
Japan	Investigational Site Number 392001	Hidaka-Shi

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of of drug related adverse events meeting the defined dose limiting toxicity at Cycle 1		3 weeks	Yes
Secondary	The number of treatment emergent adverse events		30 days after the last injection	Yes
Secondary	The number of serious adverse events		30 days after the last injection	Yes
Secondary	The number of laboratory abnormalities		30 days after the last injection	Yes
Secondary	Pharmacokinetic parameter of ombrabulin: Cmax		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of RPR258063: tmax		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of paclitaxel: Cmax		Day 1-3 at Cycle 1	No
Secondary	Pharmacokinetic parameter of carboplatin (free and total platinum): Cmax		Day 1-3 at Cycle 1	No
Secondary	Investigator determination of response		30 days after the last injection	No
Secondary	Pharmacokinetic parameter of ombrabulin: AUC		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of ombrabulin: CL		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of ombrabulin: Vss		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of ombrabulin: t 1/2		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of RPR258063: Cmax		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of RPR258063: AUC		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of RPR258063: t 1/2		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of RPR258063: Metabolic Ratio		Day 1-2 at Cycle 1	No
Secondary	Pharmacokinetic parameter of paclitaxel: AUC		Day 1-3 at Cycle 1	No
Secondary	Pharmacokinetic parameter of paclitaxel: CL		Day 1-3 at Cycle 1	No
Secondary	Pharmacokinetic parameter of paclitaxel: Vss		Day 1-3 at Cycle 1	No
Secondary	Pharmacokinetic parameter of paclitaxel: t 1/2		Day 1-3 at Cycle 1	No
Secondary	Pharmacokinetic parameter of carboplatin (free and total platinum): AUC		Day 1-3 at Cycle 1	No
Secondary	Pharmacokinetic parameter of carboplatin (free and total platinum): CL		Day 1-3 at Cycle 1	No
Secondary	Pharmacokinetic parameter of carboplatin (free and total platinum): Vss		Day 1-3 at Cycle 1	No
Secondary	Pharmacokinetic parameter of carboplatin (free and total platinum): t 1/2		Day 1-3 at Cycle 1	No