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

Temple University Health System (TUHS)

Status and phase: Completed; Phase 1

Conditions: Malignant Mesothelioma

Treatments: Biological: recombinant interferon alfa; Procedure: surgical procedure; Drug: cisplatin; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00003263

P30CA006927 (U.S. NIH Grant/Contract)

NCI-G98-1401

FCCC-96087

CDR0000066157

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)