Neoplasms, Malignant
Conditions
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.
Interventions
Pharmaceutical form:Solution for infusion Route of administration: Intravenous
DRUGbevacizumab
Pharmaceutical form:Solution for infusion Route of administration: Intravenous
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose Limiting Toxicities (DLTs) that will define the MTD | 3 weeks |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
France, Italy, United Kingdom
Outcome results
None listed