Cisplatin, Interferon Alfa, Surgery, and Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

Malignant Mesothelioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003263
• Other study ID #: CDR0000066157
• Secondary ID: P30CA006927FCCC-
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: April 16, 2013
• Start date: August 1996
• Est. completion date: November 2000

Study information

• Verified date: April 2013
• Source: Fox Chase Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Interferon alfa may interfere with the growth of cancer cells. Combining chemotherapy, radiation therapy, and interferon alfa may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of cisplatin plus interferon alfa followed by surgery and interferon alfa plus radiation therapy in treating patients with malignant pleural mesothelioma.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: November 2000
• Est. primary completion date: December 1999
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma

Intervention

Biological:
• recombinant interferon alfa
vaccine

Drug:
• cisplatin

Procedure:
• surgical procedure

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Office of S. Terry Kraus	Marrero	Louisiana
United States	Virginia Oncology Associates	Newport News	Virginia
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Fox Chase Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,