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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01193595
First received: August 31, 2010
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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

Condition Intervention Phase
Neoplasms, Malignant
Drug: Ombrabulin (AVE8062)
Drug: bevacizumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities (DLTs) that will define the MTD [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall safety profile of the combination [ Time Frame: up to a maximum follow-up of 1 year ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters of ombrabulin [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of bevacizumab [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Preliminary evidence of antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: up to a maximum follow-up of 1 year ] [ Designated as safety issue: No ]
  • Pharmacodynamic effect (biomarkers) [ Time Frame: cycle 1 ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: September 2010
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AVE8062/ bevacizumab
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)

Pharmaceutical form:Solution for infusion

Route of administration: Intravenous

Drug: bevacizumab

Pharmaceutical form:Solution for infusion

Route of administration: Intravenous


Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01193595

Locations
France
Investigational Site Number 250001
Villejuif Cedex, France, 94805
Italy
Investigational Site Number 380001
Milano, Italy, 20133
Investigational Site Number 380002
Milano, Italy, 20132
United Kingdom
Investigational Site Number 826001
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01193595     History of Changes
Other Study ID Numbers: TCD11379, 2009-017797-20
Study First Received: August 31, 2010
Last Updated: June 23, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Neoplasms
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014