ASA404 in Combination With Carboplatin/Paclitaxel/Cetuximab in Treating Patients With Refractory Solid Tumors
This phase I trial is studying the side effects and best dose of an investigational drug called DMXAA (5-6-dimethylxanthenone-4-acetic acid) or ASA404 when given together with carboplatin, paclitaxel and cetuximab to treat patients with refractory solid tumors.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of ASA 404 in Combination With Carboplatin/Paclitaxel/Cetuximab in Patients With Refractory Solid Tumors|
- Maximum tolerated dose (MTD) [ Time Frame: During cycle 1 (4 weeks) ] [ Designated as safety issue: Yes ]
- The number and percentage of subjects experiencing one or more AEs will be summarized by dose cohort, relationship to study drug, and severity [ Time Frame: Within 30 days after study treatment, or until resolution of AE ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of ASA404 in combination with other agents [ Time Frame: 48 hours after cycle 1, day 1 ] [ Designated as safety issue: No ]
- Disease response by RECIST criteria [ Time Frame: until progression ] [ Designated as safety issue: No ]
- Assess biological correlates of antitumor activity by measuring serum 5HIAA, VEGF, bFGF, PLGF, sVEGFR2, FGF 23, serum apoptotic markers (M30/M65) [ Time Frame: 4 weeks after treatment end ] [ Designated as safety issue: No ]
- DNA analysis of FGFR1 and VEGF polymorphism [ Time Frame: 4 weeks after treatment ends ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||June 2013|
|Estimated Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
- 5-6-dimethylxanthenone-4-acetic acid
Phase I 3+3 dose escalation design in patients with solid tumors who have been previously treated with chemotherapy or for whom no standard treatment options exist. Carboplatin, paclitaxel and cetuximab will be administered in standard doses. The dose of ASA404 will be escalated under predefined levels. One treatment cycle constitutes 3 weeks. A minimum of 3 patients will be entered at each treatment level, to be expanded to 6 subjects if dose limiting toxicities (DLT) are observed. If no more than one in six patients has DLT, additional patients will be enrolled at a higher dose. Once a maximum tolerated dose (MTD) has been established, the tolerability of this dose will be tested in a total of 12 patients. The anticipated sample size is 18-24 patients.
Carboplatin and paclitaxel are chosen as the chemotherapy back bone since they are commonly used in combination in multiple tumors. Cetuximab has been chosen as the EGFR inhibitor because the combination of platinum based therapy with cetuximab is effective in lung and head and neck cancers. In addition the safety and activity of carboplatin/paclitaxel with ASA 404 has already been demonstrated. A weekly schedule of ASA is chosen because 1) the safety of the weekly schedule has been tested 2) preclinical studies confirm enhanced activity with frequent administration 3) provides an opportunity to evaluate the safety and pharmacokinetics of ASA 404 with weekly cetuximab.
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|Principal Investigator:||Sarita Dubey, MD||University of California, San Francisco|