Surgery, Chemotherapy, and Intensity Modulated Radiation Therapy in Treating Patients with Stage I-III Pleural Mesothelioma

Status: Active

Description

This phase II trial studies the side effects of surgery, chemotherapy, and intensity modulated radiation therapy in treating patients with stage I-III pleural mesothelioma. Drugs used in chemotherapy, such as pemetrexed disodium, cisplatin, and carboplatin, work in different ways to stop the growth of cancer, either by killing the cancer cells, by stopping them from dividing, or by stopping them from spreading. Intensity modulated radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy before radiation therapy may help kill more tumor cells after surgery.

Eligibility Criteria

Inclusion Criteria

  • Provide written informed consent to participate on the study
  • Patients must have a pathologically confirmed diagnosis, either at MSKCC or at the participating site, of stage I-III malignant pleural mesothelioma
  • Epithelioid or biphasic histology subtype (Note: patients with biphasic histology can have < 10% sarcomatoid)
  • No evidence of metastatic disease
  • Karnofsky performance status >= 80%
  • For all patients: diffusion capacity of the lungs for carbon monoxide (DLCO) > 40% predicted (corrected for hemoglobin [Hgb])
  • For patients enrolled post-P/D, only: forced expiratory volume in 1 second (FEV1) >= 35% (corrected for Hgb) (Note: patients enrolled prior to P/D will have pulmonary function tests (PFTs) repeated pre-IMRT; if this criteria is not met, they will be removed from study)
  • In cases of concern about decreased renal function and potential high radiation dose to the kidneys, an optional nuclear medicine kidney function scan may be performed prior to radiation therapy to determine the functional contribution of each kidney
  • Absolute neutrophil count >= 1.5 K/mcL
  • Platelets >= 100 K/mcL
  • Serum total bilirubin =< 1.5 X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X ULN
  • Note: patients enrolled after chemotherapy do not have to meet the above criteria

Exclusion Criteria

  • > 10% Sarcomatoid or desmoplastic histology
  • Continuous oxygen use
  • Prior nephrectomy on the contralateral side of malignant pleural mesothelioma (MPM)
  • Prior intrapleural therapy (except pleurodesis) or intrapleural therapy at the time of P/D (i.e.: intrapleural chemotherapy, photodynamic therapy, intrapleural betadine)
  • Prior thoracic radiation therapy preventing hemithoracic pleural IMRT
  • Bulky disease in the fissure preventing lung-sparing pleural IMRT
  • Patients undergoing extrapleural pneumonectomy
  • Patients with an active infection that require systemic antibiotics, antiviral, or antifungal treatments
  • Patients with a concurrent active malignancy (except squamous or basal cell carcinoma of the skin)
  • Patients with serious unstable medical illness
  • Presence of third space fluid that cannot be controlled by drainage * For patients who develop or have baseline clinically significant pleural effusions before or during initiation of pemetrexed therapy; consideration should be given to drain the effusion prior to chemotherapy administration
  • No acute congestive heart failure
  • Pregnant or lactating women
  • Men or women not using effective contraception

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Bradford Alan Perez
Phone: 888-663-3488

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Contact: Raymond H. Mak
Phone: 617-632-3591

Minnesota

Rochester
Mayo Clinic
Status: Active
Contact: Nina Garces
Phone: 507-538-3270

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
Rockville Centre
Memorial Sloan Kettering Rockville Centre
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Daniel Gomez
Email: dgomez@mdanderson.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety and exportability of the Memorial Sloan Kettering Cancer Center (MSKCC) trimodality approach consisting of pleurectomy/decortication, adjuvant chemotherapy (neoadjuvant chemotherapy permissible as an alternative) and intensity modulated radiation therapy (IMRT) to the pleura in patients with malignant pleural mesothelioma as indicated by the incidence of >= grade 3 pneumonitis in a multi-institutional setting.

SECONDARY OBJECTIVES:

I. To determine the progression free and overall survival rates of patients with malignant pleural mesothelioma treated with lung-sparing trimodality therapy to the pleura.

II. To determine the pattern of progression: local recurrence versus metastatic disease.

III. To determine the incidence of any IMRT-related grade 2 or greater toxicity.

IV. To determine the impact of trimodality therapy and pleural IMRT on patient-reported outcomes (PRO-Common Terminology Criteria for Adverse Events [CTCAE]).

V. To develop a prediction model of resectability and a prognostic multi-modality imaging model through magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) imaging.

OUTLINE:

Patients undergo pleurectomy/decortication (P/D). Within 4-8 weeks after surgery, patients receive pemetrexed sodium intravenously (IV) over 10 minutes and cisplatin IV over 60 minutes or carboplatin IV over 30 minutes. Treatment repeats every 21 days for up to 4 courses. Within 4-8 weeks of chemotherapy completion, patients undergo 28 fractions of IMRT over approximately 6 weeks.

After completion of study treatment, patients are followed up at 1 month, then every 3 months for 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Andreas Rimner

Trial IDs

Primary ID 08-053
Secondary IDs NCI-2016-01016
Clinicaltrials.gov ID NCT00715611