Combination Chemotherapy With or Without Surgery and Chemoradiotherapy in Treating Patients With Malignant Pleural Mesothelioma

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT00354393

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as methotrexate, vinorelbine, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Cisplatin may also make tumor cells more sensitive to radiation therapy. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy with or without surgery and chemoradiotherapy works in treating patients with malignant pleural mesothelioma.

Condition or Disease	Intervention/Treatment	Phase
Malignant Mesothelioma	Drug: cisplatin Drug: methotrexate Drug: vinorelbine ditartrate Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

Assess the response to induction combination chemotherapy comprising methotrexate, vinorelbine ditartrate, and cisplatin in patients with previously untreated malignant pleural mesothelioma.

Secondary

Assess the tolerability and toxicity of this regimen in these patients.
Determine relapse-free and overall survival of patients treated with induction combination chemotherapy with or without surgery and hemithoracic radiation.
Assess the impact of induction combination chemotherapy on operability and surgical success.
Evaluate the impact of these treatment regimens on quality of life.

OUTLINE:

Induction chemotherapy: Patients receive MVP chemotherapy comprising cisplatin IV over 30-60 minutes on day 1 and vinorelbine ditartrate IV over 5-10 minutes and methotrexate IV over 5-30 minutes on days 8, 15, and 22. Treatment repeats every 28 days for 2 courses. Patients with unresectable disease may receive up to 2 additional courses of induction chemotherapy. Patients requiring palliative radiotherapy or who have progressive disease are removed from the study. Patients with resectable disease or sarcomatoid histology and T1-3, N1-2 disease with a complete or partial response to induction chemotherapy proceed to surgery.
Surgery: Patients with extensive disease undergo palliative debulking pleurectomy and decortication and then are taken off study. All other patients undergo a thoracotomy with an extrapleural pneumonectomy and then proceed to chemoradiotherapy.
Chemoradiotherapy: Beginning 6-10 weeks after surgery, patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients also receive cisplatin IV over 30-60 minutes on days 1 and 22. Patients with responding disease proceed to adjuvant chemotherapy.
Adjuvant chemotherapy: Patients receive 2 additional courses of MVP chemotherapy as above.

Quality of life is assessed at baseline, after each course of induction chemotherapy, before surgery, and then every 3 months thereafter.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Aggressive Multi-Modality Management of Malignant Pleural Mesothelioma

Study Start Date :

Aug 1, 2002

Outcome Measures

Primary Outcome Measures

Response to chemotherapy []

Secondary Outcome Measures

Tolerability and toxicity []
Relapse free and overall survival []
Operability and surgical success []
Quality of life []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed malignant pleural mesothelioma
Amenable to aggressive surgical resection, if deemed resectable
Patients with potentially resectable disease must have undergone mediastinoscopy to establish surgical stage
Resectable disease is defined as any of the following:
Epithelioid, mixed histology, or histology not otherwise specified with clinical stage I-III (T1-3, N0-2, M0) disease
Sarcomatoid histology with clinical stage I-III (T1-3, N0) disease
Intraperitoneal extension, contralateral thoracic extension, or distant metastases are eligible, but considered unresectable
Disease considered unresectable by any medical reason or if surgery was declined

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
WBC ≥ 3,000/mm³
Platelet count > 100,000/mm³
Creatinine ≤ 1.7 mg/dL
Alkaline phosphatase < 2 times normal
AST < 2 times normal
Albumin > 3 g/dL
Bilirubin < 2.0 mg/dL
Patients must be available for and compliant with adequate long-term follow-up
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception
Patients with resectable disease must have adequate pulmonary function to undergo surgery and radiotherapy
No other active malignancies