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

Neoplasms, Malignant Clinical Trial

Official title:

An Open-label, Dose-escalation, Safety and Pharmacokinetics Phase I Study of Ombrabulin in Combination With Docetaxel and Cisplatin Every 3 Weeks in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01095302
• Other study ID #: TCD11089
• Secondary ID: U1111-1116-5905
• Status: Completed
• Phase: Phase 1
• First received: March 23, 2010
• Last updated: October 12, 2013
• Start date: May 2010
• Est. completion date: December 2011

Study information

• Verified date: October 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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 docetaxel and 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, docetaxel and cisplatin in combination.

• To evaluate anti-tumor activity of the combination therapy

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

Inclusion criteria:

• Patients with advanced solid tumor for which docetaxel and cisplatin is approved such as lung cancer, epithelial ovarian cancer.

Exclusion criteria:

• Eastern Cooperative Oncology Group performance status > or = 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 < or = 1 (or alopecia < or = 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

• Patients with more than 1 line of previous chemotherapy for advanced or metastatic disease (adjuvant/neoadjuvant and targeted agents [eg gefitinib] excluded).

• Current peripheral neuropathy > or = grade 2 and ototoxicity, of any origin including significant residual symptoms due to the use of neurotoxic drugs (eg vincaalkaloids, platinum and taxanes).

• 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 fundoscopic 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 Design

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

Related Conditions & MeSH terms

• Neoplasms
• Neoplasms, Malignant

Intervention

Drug:
• OMBRABULIN (AVE8062)
Pharmaceutical form:injection solution Route of administration: intravenous infusion
• cisplatin
Pharmaceutical form:injection solution Route of administration: intravenous infusion
• docetaxel
Pharmaceutical form:injection solution Route of administration: intravenous infusion

Locations

Country	Name	City	State
Japan	Investigational Site Number 392003	Akashi-Shi
Japan	Investigational Site Number 392001	Koto-Ku
Japan	Investigational Site Number 392002	Nagoya-Shi

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity		3 weeks (cycle 1)	Yes
Secondary	Global safety profile based on treatment emergent adverse events, serious adverse events, and laboratory abnormalities		on-treatment period + 30 days	Yes
Secondary	Pharmacokinetic profiles of all study drugs and AVE8062 active metabolite based on PK parameters (Cmax, AUC, t1/2, CL, Vss).		Cycle 1: Day 1 and 3; up to Cycle 4: Day 1	No
Secondary	Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)		on-treatment period + 30 days	No