Safety and Effectiveness of Combretastatin A-4 Phosphate Combined With Chemotherapy in Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized Open-Labeled Phase II Study of Combretastatin A-4 Phosphate in Combination With Paclitaxel and Carboplatin to Evaluate the Safety and Efficacy in Subjects With Advanced Imageable Malignancies

Conditions
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Cancer, Tumor

Intervention / Treatment
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* Drug: Combretastatin A-4 Phosphate + Paclitaxel + Carboplatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 45 mg/m2 Combretastatin A-4 Phosphate<br> | Drug: Combretastatin A-4 Phosphate + Paclitaxel + Carboplatin<br>* Combretastatin A-4 Phosphate is administered IV at 45 mg/m2 or 60 mg/m2 on Days 1, 8 and 15 followed by paclitaxel (3 hour infusion at 200 mg/m2) and carboplatin (1 hour infusion at AUC = 6) on Day 2 of each cycle. The treatment cycle is 21 days with a maximum of 21 days. Following cycle 6, subjects that have not progressed may continue on CA4P monotherapy, which will be administered at 45 mg/m2 or 60 mg/m2 on Days 1 and 8 with rest on Day 15, repeated every 21 days until disease progression.<br>* Other names: carboplatin;|
| Experimental: 60 mg/m2 Combretastatin A-4 Phosphate<br> | Drug: Combretastatin A-4 Phosphate + Paclitaxel + Carboplatin<br>* Combretastatin A-4 Phosphate is administered IV at 45 mg/m2 or 60 mg/m2 on Days 1, 8 and 15 followed by paclitaxel (3 hour infusion at 200 mg/m2) and carboplatin (1 hour infusion at AUC = 6) on Day 2 of each cycle. The treatment cycle is 21 days with a maximum of 21 days. Following cycle 6, subjects that have not progressed may continue on CA4P monotherapy, which will be administered at 45 mg/m2 or 60 mg/m2 on Days 1 and 8 with rest on Day 15, repeated every 21 days until disease progression.<br>* Other names: carboplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety of the CA4P-paclitaxel-carboplatin combination in advanced imageable malignancies |  | From first administration of study drug through approximately 30 days following last dose of study drug | 
| To evaluate tumor response |  | From baseline through end of study visit | 
| To establish the Recommended Phase II Dose (RP3D) for the combination of CA4P-paclitaxel-carboplatin in advanced imageable malignancies |  | from first study drug administration through end of study visit | 
| To assess the change in tumor blood flow by use of MRI in advanced imageable malignancies |  | from screening through end of study visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, tumor, imageable, CA4P, Combretastatin, Combretastatin A4 Phosphate, Combretastatin A-4 Phosphate, Carboplatin, Paclitaxel, carbo, taxol