Clinical trial NCT01193595: Dose-escalation, Safety, Pharmacokinetics Study of AVE8062 Combined With Bevacizumab in Patients With Advanced Solid Tumors
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms, Malignant
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-09-02
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs) that will define the MTD
timeFrame: 3 weeks
Secondary outcomes:
measure: Overall safety profile of the combination
timeFrame: up to a maximum follow-up of 1 year
measure: Pharmacokinetic parameters of ombrabulin
timeFrame: 6 weeks
measure: Pharmacokinetic parameters of bevacizumab
timeFrame: 6 weeks
measure: Preliminary evidence of antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: up to a maximum follow-up of 1 year
measure: Pharmacodynamic effect (biomarkers)
timeFrame: cycle 1
Other outcomes:
Locations:
city: Villejuif Cedex
country: France
facility: Investigational Site Number 250001
city: Milano
country: Italy
facility: Investigational Site Number 380002
city: Milano
country: Italy
facility: Investigational Site Number 380001
city: Sutton
country: United Kingdom
facility: Investigational Site Number 826001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: