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

Phase 2

Completed

• Conditions: Malignant Mesothelioma
• Interventions: 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

• Registration Number: NCT00354393
• Lead Sponsor: The Cleveland Clinic

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2002-08
• Study First Submitted: 2006-07-19
• Study First Submitted QC: 2006-07-19
• Study First Posted: 2006-07-20
• Primary Completion: 2009-06
• Study Completion: 2009-06
• Status Verified: 2023-05
• Last Update Submitted: 2023-08-28
• Last Update Posted: 2023-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Induction Combination Chemotherapy	Cisplatin	Induction chemotherapy: Patients get MVP chemo. Treatment repeats every 28 days for 2 courses. Patients w/ unresectable disease may get up to 2 add'l courses of induction chemo. Patients requiring palliative radiotherapy or have PD are removed from study. Patients w/ resectable disease or sarcomatoid histology \& T1-3, N1-2 disease w/ a CR or PR to induction chemo go to surgery. Surgery: Patients w/ extensive disease get palliative debulking pleurectomy and decortication \& are taken off study. Other patients undergo a thoracotomy w/ extrapleural pneumonectomy \& proceed to chemoradiotherapy. Chemoradiotherapy: At 6-10 weeks post-op, patients get 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients receive cisplatin IV over 30-60 minutes days 1 \& 22. Patients w/ responding disease proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients get 2 more courses of MVP chemotherapy
Induction Combination Chemotherapy	Adjuvant therapy	Induction chemotherapy: Patients get MVP chemo. Treatment repeats every 28 days for 2 courses. Patients w/ unresectable disease may get up to 2 add'l courses of induction chemo. Patients requiring palliative radiotherapy or have PD are removed from study. Patients w/ resectable disease or sarcomatoid histology \& T1-3, N1-2 disease w/ a CR or PR to induction chemo go to surgery. Surgery: Patients w/ extensive disease get palliative debulking pleurectomy and decortication \& are taken off study. Other patients undergo a thoracotomy w/ extrapleural pneumonectomy \& proceed to chemoradiotherapy. Chemoradiotherapy: At 6-10 weeks post-op, patients get 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients receive cisplatin IV over 30-60 minutes days 1 \& 22. Patients w/ responding disease proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients get 2 more courses of MVP chemotherapy
Induction Combination Chemotherapy	Conventional surgery	Induction chemotherapy: Patients get MVP chemo. Treatment repeats every 28 days for 2 courses. Patients w/ unresectable disease may get up to 2 add'l courses of induction chemo. Patients requiring palliative radiotherapy or have PD are removed from study. Patients w/ resectable disease or sarcomatoid histology \& T1-3, N1-2 disease w/ a CR or PR to induction chemo go to surgery. Surgery: Patients w/ extensive disease get palliative debulking pleurectomy and decortication \& are taken off study. Other patients undergo a thoracotomy w/ extrapleural pneumonectomy \& proceed to chemoradiotherapy. Chemoradiotherapy: At 6-10 weeks post-op, patients get 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients receive cisplatin IV over 30-60 minutes days 1 \& 22. Patients w/ responding disease proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients get 2 more courses of MVP chemotherapy
Induction Combination Chemotherapy	Neoadjuvant Therapy	Induction chemotherapy: Patients get MVP chemo. Treatment repeats every 28 days for 2 courses. Patients w/ unresectable disease may get up to 2 add'l courses of induction chemo. Patients requiring palliative radiotherapy or have PD are removed from study. Patients w/ resectable disease or sarcomatoid histology \& T1-3, N1-2 disease w/ a CR or PR to induction chemo go to surgery. Surgery: Patients w/ extensive disease get palliative debulking pleurectomy and decortication \& are taken off study. Other patients undergo a thoracotomy w/ extrapleural pneumonectomy \& proceed to chemoradiotherapy. Chemoradiotherapy: At 6-10 weeks post-op, patients get 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients receive cisplatin IV over 30-60 minutes days 1 \& 22. Patients w/ responding disease proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients get 2 more courses of MVP chemotherapy
Induction Combination Chemotherapy	Intensity-modulated radiation therapy	Induction chemotherapy: Patients get MVP chemo. Treatment repeats every 28 days for 2 courses. Patients w/ unresectable disease may get up to 2 add'l courses of induction chemo. Patients requiring palliative radiotherapy or have PD are removed from study. Patients w/ resectable disease or sarcomatoid histology \& T1-3, N1-2 disease w/ a CR or PR to induction chemo go to surgery. Surgery: Patients w/ extensive disease get palliative debulking pleurectomy and decortication \& are taken off study. Other patients undergo a thoracotomy w/ extrapleural pneumonectomy \& proceed to chemoradiotherapy. Chemoradiotherapy: At 6-10 weeks post-op, patients get 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients receive cisplatin IV over 30-60 minutes days 1 \& 22. Patients w/ responding disease proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients get 2 more courses of MVP chemotherapy
Induction Combination Chemotherapy	3-dimensional conformal radiation therapy	Induction chemotherapy: Patients get MVP chemo. Treatment repeats every 28 days for 2 courses. Patients w/ unresectable disease may get up to 2 add'l courses of induction chemo. Patients requiring palliative radiotherapy or have PD are removed from study. Patients w/ resectable disease or sarcomatoid histology \& T1-3, N1-2 disease w/ a CR or PR to induction chemo go to surgery. Surgery: Patients w/ extensive disease get palliative debulking pleurectomy and decortication \& are taken off study. Other patients undergo a thoracotomy w/ extrapleural pneumonectomy \& proceed to chemoradiotherapy. Chemoradiotherapy: At 6-10 weeks post-op, patients get 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients receive cisplatin IV over 30-60 minutes days 1 \& 22. Patients w/ responding disease proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients get 2 more courses of MVP chemotherapy
Induction Combination Chemotherapy	Vinorelbine ditartrate	Induction chemotherapy: Patients get MVP chemo. Treatment repeats every 28 days for 2 courses. Patients w/ unresectable disease may get up to 2 add'l courses of induction chemo. Patients requiring palliative radiotherapy or have PD are removed from study. Patients w/ resectable disease or sarcomatoid histology \& T1-3, N1-2 disease w/ a CR or PR to induction chemo go to surgery. Surgery: Patients w/ extensive disease get palliative debulking pleurectomy and decortication \& are taken off study. Other patients undergo a thoracotomy w/ extrapleural pneumonectomy \& proceed to chemoradiotherapy. Chemoradiotherapy: At 6-10 weeks post-op, patients get 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients receive cisplatin IV over 30-60 minutes days 1 \& 22. Patients w/ responding disease proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients get 2 more courses of MVP chemotherapy
Induction Combination Chemotherapy	Methotrexate	Induction chemotherapy: Patients get MVP chemo. Treatment repeats every 28 days for 2 courses. Patients w/ unresectable disease may get up to 2 add'l courses of induction chemo. Patients requiring palliative radiotherapy or have PD are removed from study. Patients w/ resectable disease or sarcomatoid histology \& T1-3, N1-2 disease w/ a CR or PR to induction chemo go to surgery. Surgery: Patients w/ extensive disease get palliative debulking pleurectomy and decortication \& are taken off study. Other patients undergo a thoracotomy w/ extrapleural pneumonectomy \& proceed to chemoradiotherapy. Chemoradiotherapy: At 6-10 weeks post-op, patients get 3-dimensional conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients receive cisplatin IV over 30-60 minutes days 1 \& 22. Patients w/ responding disease proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients get 2 more courses of MVP chemotherapy

Primary Outcome Measures

Name	Time	Method
Best Response	After 2-4 cycles of induction chemotherapy (28 day cycle)	Best response to chemotherapy after induction

Secondary Outcome Measures

Name	Time	Method
Tolerability and toxicity	After 2-4 cycles of induction chemotherapy (28 day cycle)	Toxicity related to induction chemotherapy
Relapse free and overall survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first	Time to relapse and overall survival
Assess Patient Quality of Life	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)	Patient Quality of Life during induction chemotherapy

Trial Locations

Locations (1)

Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States