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

NCT01293630 | Completed Phase 1

• 2 other identifiers: TCD11270U1111-1115-2568
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• The number of of drug related adverse events meeting the defined dose limiting toxicity at Cycle 1

  3 weeks

Secondary Outcomes (24)

• 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

Study Arms (1)

Cohort - 1 through 5

EXPERIMENTAL

AVE8062 combined with paclitaxel and carboplatin will be administered once every 3 weeks

Drug: Ombrabulin (AVE8062); Drug: Paclitaxel; Drug: Carboplatin

Interventions

Ombrabulin (AVE8062) DRUG

Pharmaceutical form:solution Route of administration: intravenous

Cohort - 1 through 5

Paclitaxel DRUG

Pharmaceutical form:solution Route of administration: intravenous

Cohort - 1 through 5

Carboplatin DRUG

Pharmaceutical form:solution Route of administration: intravenous

Cohort - 1 through 5

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

Investigational Site Number 392002

Akashi-Shi, Japan

Location

Investigational Site Number 392001

Hidaka-Shi, Japan

Location

Related Publications (1)

• Matsumoto K, Sunaga Y, Ecstein-Fraisse E, Fujiwara K. Phase I study of ombrabulin in combination with paclitaxel and carboplatin in Japanese patients with advanced solid tumors. Int J Gynecol Cancer. 2024 Apr 1;34(4):586-593. doi: 10.1136/ijgc-2022-003880.

  PMID: 37989482 DERIVED

MeSH Terms

Interventions

AC 7700; Paclitaxel; Carboplatin

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2011
• First Posted: February 10, 2011
• Study Start: January 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 30, 2015

Record last verified: 2015-10

Locations

JP (2)