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

NeuroTherapia, Inc.

Status and phase

Completed

Phase 2

Conditions

Malignant Mesothelioma

Treatments

Procedure: Adjuvant therapy

Radiation: 3-dimensional conformal radiation therapy

Drug: Methotrexate

Drug: Cisplatin

Procedure: Neoadjuvant Therapy

Radiation: Intensity-modulated radiation therapy

Procedure: Conventional surgery

Drug: Vinorelbine ditartrate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00354393

CASE-CCF-IRB-5179

P30CA043703 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

9 patients

Sex

All

Ages

Under 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

9 participants in 1 patient group

Induction Combination Chemotherapy

Experimental group

Description:

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

Treatment: