An Open Label, Dose Escalation, Safety and Pharmacokinetics Phase 1 Study With Ombrabulin Administered as a 30-minute Intravenous Infusion in Combination With Cisplatin Administered as an Intravenous Infusion Every 3 Weeks in Patients With Advanced Solid Tumors
Inclusion criteria :
- Advanced solid tumor that has become refractory to conventional treatment or for
which no standard therapy exists.
Exclusion criteria :
- Eastern Cooperative Oncology Group performance status ≥ 2.
- Concurrent treatment with any other anticancer therapy
- Male or female patients who do not agree with contraception.
- Washout period of less than 28 days from prior anticancer therapies (chemotherapy,
targeted agents, immunotherapy and radiotherapy) or any investigational treatment,
except for nitrosoureas, mitomycin which may not be used up to 42 days prior to the
first cycle.No washout period is required for hormonal therapy that has to be
discontinued before the first cycle.
- Not recovered from all previous therapies (radiation, surgery, and medications).
Adverse events related to previous therapies must be National Cancer Institute Common
Terminology Criteria (NCI-CTCAE V3.0) grade≤1 (or alopecia≤grade 2) at screening or
returned to the subject's baseline prior to their most recent previous therapy.
- Symptomatic brain metastases and carcinomatous leptomeningitis.
- Other serious illness or medical conditions not controlled by adequate treatment
- Previous cumulative carboplatin dose higher than 3,000 mg/m2 or cisplatin higher than
- Patients whose disease has progressed or has recurred in less than 6 months from the
completion of the previous platinum containing chemotherapy
- Known platinum compound hypersensitivity.
- Neuropathy and ototoxicity due to previous platinum chemotherapy.
- Inadequate organ function
- Documented medical history of myocardial infarction, documented angina pectoris,
arrhythmia especially severe conduction disorder such as second or third degree
atrio-ventricular block, stroke, or history of arterial or venous thrombo-embolism
within the past 180 days requiring anticoagulants.
- Patient with a left ventricular ejection fraction<50% by echocardiography.
- Patients with a baseline QTc interval>0.45, or family history of Long QT Syndrome.
- Patient with uncontrolled hypertension and patient with organ damage related to
hypertension such as left ventricular hypertrophy or grade 2 ocular fundscopic
changes or kidney impairment.
- Patients with growing vessel disease (eg age-related macular degeneration, diabetic
retinopathy, rheumatoid arthritis), or ongoing wound healing process. Patients should
be enrolled in the study at least 28 days after surgery
- 12-lead Electrocardiogram: ST- and T-wave changes suggesting ischemia
- Hypertension defined as systolic blood pressure (BP)>140 mmHg or diastolic BP>90 mmHg
on two repeated measurements at 30 minutes intervals.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.