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

Malignant Mesothelioma Clinical Trial

Official title:

Aggressive Multi-Modality Management of Malignant Pleural Mesothelioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00354393
• Other study ID #: CASE-CCF-IRB-5179
• Secondary ID: P30CA043703CASE-
• Status: Completed
• Phase: Phase 2
• Start date: August 2002
• Est. completion date: June 2009

Study information

• Verified date: May 2023
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

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

PRIOR CONCURRENT THERAPY:

• No prior surgical resection, radiation therapy, chemotherapy, or immunotherapy for this cancer

Related Conditions & MeSH terms

• Malignant Mesothelioma
• Mesothelioma
• Mesothelioma, Malignant

Intervention

Drug:
• Cisplatin

• Methotrexate

• Vinorelbine ditartrate

Procedure:
• Adjuvant therapy

• Conventional surgery

• Neoadjuvant Therapy

Radiation:
• 3-dimensional conformal radiation therapy

• Intensity-modulated radiation therapy

Locations

Country	Name	City	State
United States	Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
The Cleveland Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Response	Best response to chemotherapy after induction	After 2-4 cycles of induction chemotherapy (28 day cycle)
Secondary	Tolerability and toxicity	Toxicity related to induction chemotherapy	After 2-4 cycles of induction chemotherapy (28 day cycle)
Secondary	Relapse free and overall survival	Time to relapse and overall survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first
Secondary	Assess Patient Quality of Life	Patient Quality of Life during induction chemotherapy	Prior to initiation of each cycle of therapy, and every 3 months after completion of therapy until death, withdrawal or loss to follow up (Average 10 years)