This is a study evaluating the safety and effectiveness of Combretastatin A4 Phosphate (CA4P) combined with the chemotherapy drugs, carboplatin and paclitaxel. The full treatment and observation time should be about 5 months. During this time the patient should receive 18 CA4P infusions and 6 carboplatin followed by paclitaxel treatments. Patients will be randomized into one of two CA4P dose-level groups in order to recommend a preferred dose-level for future studies. At least 2 dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) scans will be conducted to monitor the blood flow through the tumor before and after treatment with CA4P.

This is a phase II study evaluating the safety and efficacy of Combretastatin A4 Phosphate (CA4P) combined with carboplatin and paclitaxel. Treatment is for a maximum of 6 consecutive 21-day cycles. Patients are randomized onto one of two CA4P dosing arms (45 or 63 mg/m2). CA4P is administered on days 1, 8 and 15 of each cycle. Carboplatin and paclitaxel (AUC 6 and 200 mg/m2, respectively) are administered on day 2 of each cycle. At least 2 DCE-MRI scans will be performed to evaluate the change in tumor blood flow following treatment with CA4P.

Inclusion Criteria:

• Advanced malignancy where treatment with carboplatin and paclitaxel is warranted.
• Minimum 28-day interval from any surgical, chemotherapy or immunotherapy treatment and a 14-day interval from radiotherapy treatment.
• Radiologically measurable disease to meet MRI perfusion criteria.
• ECOG performance status less than or equal to 1.
• Life expectancy greater than 12 weeks.
• Normal ejection fraction.

Exclusion Criteria:

• Uncontrolled brain metastasis.
• Significant cardiac abnormalities.
• Prior radiotherapy at the tumor site.
• Symptomatic peripheral vascular or cerebrovascular disease.
• Uncontrolled hypertension.