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

NCT01193595 | Completed Phase 1

• 2 other identifiers: TCD113792009-017797-20
• Study Type: interventional
• Target: 39
• Locations: 3 countries
• Sites: 4

Brief 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

Conditions

Neoplasms, Malignant

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting Toxicities (DLTs) that will define the MTD

  3 weeks

Secondary Outcomes (5)

• Overall safety profile of the combination

  up to a maximum follow-up of 1 year

• Pharmacokinetic parameters of ombrabulin

  6 weeks

• Pharmacokinetic parameters of bevacizumab

  6 weeks

• 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

• Pharmacodynamic effect (biomarkers)

  cycle 1

Study Arms (1)

AVE8062/ bevacizumab

EXPERIMENTAL

The combination of ombrabulin and bevacizumab will be administered every 3 weeks according to the following schedule: One day 1, ombrabulin will be administered as a 30 minutes intravenous (i.v) infusion. Bevacizumab will be administered as a 30-90 minutes i.v. infusion 24 hours after the end of ombrabulin infusion on day 2.

Drug: Ombrabulin (AVE8062); Drug: bevacizumab

Interventions

Ombrabulin (AVE8062) DRUG

Pharmaceutical form:Solution for infusion Route of administration: Intravenous

AVE8062/ bevacizumab

bevacizumab DRUG

Pharmaceutical form:Solution for infusion Route of administration: Intravenous

AVE8062/ bevacizumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (4)

Investigational Site Number 250001

Villejuif, 94805, France

Location

Investigational Site Number 380002

Milan, 20132, Italy

Location

Investigational Site Number 380001

Milan, 20133, Italy

Location

Investigational Site Number 826001

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

AC 7700; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 31, 2010
• First Posted: September 2, 2010
• Study Start: September 1, 2010
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: December 3, 2014

Record last verified: 2014-12

Locations

IT (2); FR (1); GB (1)