Phase I Combined Modality Protocol for Malignant Mesothelioma: Cisplatin & rIFN-alpha-2b Followed by Surgical Resection (Debulking), and Post-Op Concurrent Chemoradiotherapy With Cisplatin, +/- rIFN-alpha-2b
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of neoadjuvant interferon alfa 2b
(IFN-A2b) administered with cisplatin in patients with malignant pleural mesothelioma. II.
Determine the MTD of IFN-A2b administered with radiation therapy and cisplatin after surgery
in these patients. III. Determine the response rate and toxicity of induction therapy with
IFN-A2b and cisplatin in these patients. IV. Determine the toxicity of concurrent radiation
therapy, cisplatin, and IFN-A2b after surgery in these patients. V. Determine the local
control rate, freedom from progression, median survival, and long term survival of these
patients after combined modality therapy.
OUTLINE: This is a dose escalation study. Patients receive induction therapy consisting of
cisplatin IV weekly and interferon alfa 2b (IFN-A2b) subcutaneously three times a week for 6
weeks. Patients who experience at least 25% tumor shrinkage receive another 4 weeks of
therapy. Patients then undergo debulking surgery to remove all gross tumor, if possible. If
this resection is performed, then patients begin radiation therapy 2-6 weeks after surgery.
Patients with unresectable tumors begin radiation therapy 2-4 weeks after the last course of
induction chemotherapy. Patients undergo radiation therapy 5 days a week for 6 weeks.
Concurrently, patients receive cisplatin IV weekly and IFN-A2b subcutaneously three times a
week. Cohorts of 4 patients each receive escalated doses of IFN-A2b during induction
chemotherapy. Once the maximum tolerated dose (MTD) of IFN-A2b is established, one dose
level below this dose is used for the beginning doses of IFN-A2b during adjuvant
chemotherapy. If no unacceptable toxic effects occur, then the dose of IFN-A2b is escalated
to the induction MTD. Patients are followed at 3-6 weeks after completing radiochemotherapy,
then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study within 2-3 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Corey J. Langer, MD
Fox Chase Cancer Center
United States: Federal Government
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