Surgery, Chemotherapy, and Intensity Modulated Radiation Therapy in Treating Patients with Stage I-III Pleural Mesothelioma
Basic Trial Information
|Phase II||Treatment||Active||18 and over||08-053|
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.
Further Study Information
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.
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.
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.
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
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 prior to P/D, only: forced expiratory volume in 1 second (FEV1) >= 35% (corrected for Hgb) of predicted postoperative (ppoFEV1) (as if the patient underwent a pneumonectomy) based on the following formula using the quantitative ventilation/perfusion (V/Q) scan:
Predicted post-resection FEV1 = FEV1 x % perfusion to uninvolved lung from the quantitative V/Q scan report
For patients enrolled post-P/D, only: FEV1 >= 35% (corrected for Hgb)
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
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
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Memorial Sloan-Kettering Cancer Center
- National Cancer Institute
Memorial Sloan Kettering Cancer Center at Basking Ridge
Memorial Sloan Kettering Monmouth Monmouth
Memorial Sloan Kettering Cancer Center Commack
Memorial Sloan-Kettering Cancer Center
Memorial Sloan Kettering Cancer Center Rockville Centre
Memorial Sloan-Kettering Cancer Center West Harrison
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00715611
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.