Dose-escalation, Safety, Pharmacokinetics Study of AVE8062 Combined With Bevacizumab in Patients With Advanced Solid Tumors

Neoplasms, Malignant Clinical Trial

Official title:

An Open-label, Non-randomized, Dose Escalation, Safety and Pharmacokinetic Phase I Study of Ombrabulin (AVE8062) in Combination With Bevacizumab Administered by Intravenous Infusion Every 3 Weeks in Patients With Advanced Solid Tumors.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01193595
• Other study ID #: TCD11379
• Secondary ID: 2009-017797-20
• Status: Completed
• Phase: Phase 1
• First received: August 31, 2010
• Last updated: December 2, 2014
• Start date: September 2010
• Est. completion date: October 2014

Study information

• Verified date: December 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

• To determine the maximum administered dose (MAD) and the maximum tolerated dose (MTD) of ombrabulin in combination with best tolerated dose of bevacizumab based on the incidence of related Dose Limiting Toxicities (DLTs).

Secondary Objectives:

• To assess the overall safety profile of the combination

• To characterize the pharmacokinetic (PK) profile of both ombrabulin and bevacizumab when given in combination

• To evaluate preliminary evidence of anti-tumor activity

• To assess the pharmacodynamic effect using (Dynamic Contrast Enhanced Ultra-Sound) DCE-US, measuring biomarkers

Description:

The duration of the study for each patient will include an up to 28-day screening phase, 21-day study treatment cycles, an end of treatment visit with a follow-up period. Each patient will participate in only one dose group and will receive AVE8062 with bevacizumab every 3 weeks until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Histologically or cytologically proven solid malignant tumor at the first diagnosis with the exception of squamous non small cell lung cancer (NSCLC).

• Advanced neoplastic disease (i.e. metastatic or locally unresectable advanced disease)

• Presence of one measurable lesion at baseline in the MTD expanded cohort

Exclusion criteria:

• ECOG (Eastern cooperativeOncology Group) performance status > 1

• Concurrent treatment with any other anticancer therapy

• Pericardial effusion requiring intervention (drainage)

• History of brain metastasis, spinal cord compression or carcinomatous meningitis or new evidence of brain metastasis on screening Computed tomography (CT) or Magnetic resonance imaging (MRI) scan

• Diagnosis of squamous Non Squamous Cell Lung Cancer (NSCLC) or with mixed cell type with predominant squamocellular histology

• Hormone sensitive prostate cancer

• Abdominal Radiotherapy

• Major surgery within the last month of study enrollment or surgical wound not fully healed before study enrollment

• High cumulative doses of anthracycline

• Inadequate organ function

• Inadequate hematology function or poor bone marrow reserve

• Any of the following within 6 months prior to study enrollment: peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease and diverticulitis

• Any history or underlying cardiac condition that may increase the risks associated with the study participation or administration of the investigational products, or that may interfere with the interpretation of the results.

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:Solution for infusion Route of administration: Intravenous
• bevacizumab
Pharmaceutical form:Solution for infusion Route of administration: Intravenous

Locations

Country	Name	City	State
France	Investigational Site Number 250001	Villejuif Cedex
Italy	Investigational Site Number 380001	Milano
Italy	Investigational Site Number 380002	Milano
United Kingdom	Investigational Site Number 826001	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

France,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities (DLTs) that will define the MTD		3 weeks	Yes
Secondary	Overall safety profile of the combination		up to a maximum follow-up of 1 year	Yes
Secondary	Pharmacokinetic parameters of ombrabulin		6 weeks	No
Secondary	Pharmacokinetic parameters of bevacizumab		6 weeks	No
Secondary	Preliminary evidence of antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)		up to a maximum follow-up of 1 year	No
Secondary	Pharmacodynamic effect (biomarkers)		cycle 1	No