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
18 Years
N/A
Both
Malignant Mesothelioma
Trial Information
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven ipsilateral malignant pleural mesothelioma
- No contralateral thoracic or intra-abdominal involvement
- No distant metastases
PATIENT CHARACTERISTICS:
- Age: 18 and over
- Performance status: ECOG 0 or 1
- Life expectancy: Not specified
- Hematopoietic:
- Absolute neutrophil count greater than 2,000/mm3
- Platelet count greater than 100,000/mm3
- No symptomatic anemia requiring transfusion
- Hepatic:
- Bilirubin less than 2.0 mg/dL
- No autoimmune hepatitis
- No history of decompensated liver disease; e.g. esophageal varices
- Ascites
- Albumin at least 2.5 mg/dL
- Increasing prothrombin time of at least 2.0
- Renal: Creatinine no greater than 1.5 mg/dL
- Cardiovascular:
- No symptomatic or debilitating cardiovascular disease,
- No concurrent thrombophlebitic or embolic disorders
- Pulmonary:
- No symptomatic or debilitating pulmonary disease,
- Pretreatment diffusion capacity greater than 30% of predicted normal
- Projected post-treatment FEV1 at least 1.0 L
- Other:
- No prior malignancy within 3 years, except nonmelanomatous skin cancer
- Carcinoma in situ of the cervix
- Ductal carcinoma in situ of the breast
- Not pregnant
- Fertile patients must use effective contraception
- No history of hypersensitivity to interferon or any component of the injection
- No uncontrolled diabetes (blood sugars consistently at least 300 mg/dL)
- No insulin dependent diabetes mellitus with history of ketoacidosis within 1
year
- No psychosis
- No uncontrolled thyroid abnormalities
- No active infection requiring intravenous antibiotics
PRIOR CONCURRENT THERAPY:
- Biologic therapy: No prior biologic therapy
- Chemotherapy: No prior chemotherapy
- Endocrine therapy: Not specified
- Radiotherapy: No prior radiotherapy
- Surgery:
- No prior debulking surgery
- No prior chest tube drainage with sclerosis if tumor resectable
- Prior thoracentesis allowed
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Corey J. Langer, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Fox Chase Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000066157
NCT ID:
NCT00003263
Start Date:
August 1996
Completion Date:
November 2000
Related Keywords:
- Malignant Mesothelioma
- localized malignant mesothelioma
- Mesothelioma
Name | Location |
|---|---|
| Fox Chase Cancer Center | Philadelphia, Pennsylvania 19111 |
| Virginia Oncology Associates | Newport News, Virginia 23606 |
| Office of S. Terry Kraus | Marrero, Louisiana 70072 |
