An Open-label, Dose Escalation, Safety and Pharmacokinetics Phase 1 Study With AVE8062 Administered as a 30-minute Intravenous Infusion Every 3 Weeks in Patients With Advanced Solid Tumors.
- Advanced solid tumor that has become refractory to conventional treatment or for
which no standard therapy exists.
- Patients with signed and dated Institutional Review Board (IRB)-approved patient
informed consent form (ICF) prior to enrollment in the study.
- Eastern Cooperative Oncology Group performance status > or = 2.
- Life expectancy of less than 12 weeks.
- Concurrent treatment with any other anticancer therapy, including chemotherapy,
immunotherapy, radiotherapy, targeted therapy, gene therapy, or patients planning to
receive these treatments during the study.
- Absence of histologically or cytologically proven cancer.
- Male patients who do not agree with contraception. Absence of negative serum/urinary
pregnancy test within the 7 days prior to the enrollment in the study for female
patients with childbearing potential. Patients must be post-menopausal, surgically
sterile, or using "effective contraception" (the definition of "effective
contraception" will be based on the judgment of the investigator).
- Washout period of less than 28 days from prior antitumor therapy (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, however, it must 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 grade < or = 1 (or alopecia < or = 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:
- Existence of significant neurologic or psychiatric disorders impairing the
ability to obtain consent.
- Active infection.
- Other serious illness not controlled by adequate treatment.
- Inadequate organ function including:
- Absolute neutrophils counts<1.5 x 10^9/L
- Platelets counts<100 x 10^9/L
- Hemoglobin<9.0 g/dL (without red blood cells transfusion during 28 days prior to
- Calculated creatinin clearance<60 ml/min
- Total bilirubin > or = 1.5 mg/dL
- Alanine aminotransferase/aspartate aminotransferase>1.5 times the upper normal
limits of the institutional norms.
- Alkaline phosphatase (AP)>2.5 times the upper normal limits of the institutional
norms. An increase of AP up to grade 2 would be accepted only if this increase
is related to the presence of bone metastases. Bone specific isoenzyme AP should
be greater than the pathological limit defined by the manufacturer as a sign of
- 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.
- Patient with a baseline QTc interval of >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 funduscopic
changes or kidney impairment.
- Patient with growing vessel disease (eg age-related macular degeneration, diabetic
retinopathy, rheumatoid arthritis), or ongoing wound healing process. Patient 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.
- Patient with one or more episodes of ventricular tachycardia with 3 or more
consecutive premature beats, with a frequency > or = 180 beats/min.