Malignant Pleural Mesothelioma
Conditions
Keywords
Pemetrexed, Cisplatin, Intensity Modulated Radiation Therapy, 15-304
Brief summary
The purpose of this study is to evaluate the safety of combining chemotherapy at different doses with a specific type of radiation therapy delivered to the entire lining of the lung to find out what effects, if any, it has on people. This radiation technique is called pleural intensity modulated radiation therapy (IMRT). IMRT specifically targets the lining of the lung (pleura) where the cancer is and reduces the risk of damaging the lung itself. When given after chemotherapy, pleural IMRT has demonstrated promising results with respect to keeping mesothelioma under control longer. However, the investigators want to determine if giving pleural IMRT at the same time as chemotherapy is safe. If safe, further studies will be done to see if chemotherapy and pleural IMRT given at the same time keeps the tumor under control for a longer period of time than chemotherapy followed by pleural IMRT.
Interventions
Dose escalation of pemetrexed and cisplatin will follow the dose levels. The escalation will not exceed 500 mg/m\^2 for pemetrexed in combination with 75 mg/m\^2 of cisplatin even if the maximum tolerated dose is not identified. Each treatment cycle of chemotherapy will be 21 days. Patients will receive up to 2 cycles of chemotherapy during the radiation, and be followed for any DLT during the radiation therapy and for 12 weeks afterwards.
RADIATIONPleural Intensity Modulated Radiation Therapy
Pleura intensity modulated radiation therapy (IMRT) will be administered over approximately 6 weeks at 50.4 Gy in 28 fractions. The prescription radiation dose may anywhere between 45 and 50.4 Gy in 25 fractions if necessary to meet the normal tissue dose constraints.
DEVICEMRI
A pre-treatment MRI before chemo-RT will be acquired and will be used for target delineation. A three month post-treatment MRI will be acquired with the same protocol to assess the response from concurrent chemo-RT.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed diagnosis of malignant pleural mesothelioma at MSKCC * No plans for surgical resection * Stage T1-4, N0-3, M0 * No prior radiation therapy to the chest, breast or supraclavicular fossa that would limit radiation delivery to the full prescription dose * Prior chemotherapy regimens ≤1 * Age ≥18 years * Karnofsky performance status ≥ 80% * Pulmonary function tests as follows: DLCO\>50% predicted * Adequate hematologic, hepatic, and renal function as indicated by the following laboratory values * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Calculated creatinine clearance (CrCl) ≥ 45mL/min (using Cockcroft & Gault method) * Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless known Gilbert's disease) * AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN
Exclusion criteria
* Pregnant or lactating women, or men or women not using effective contraception * Patients with an active infection that requires systemic antibiotics, antiviral, or antifungal treatments * Patients with a concurrent active malignancy (with the exception of skin cancer) * Patients with serious unstable medical illness * Patients with idiopathic pulmonary fibrosis * Patients with NYHA heart failure class \>2 * Patients with only one kidney that is ipsilateral to the mesothelioma * Implanted pacemaker and/or defibrillator ipsilateral to the mesothelioma if it cannot be moved * Patients meeting the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicities (DLT) | up to 12 weeks | The NCI Common Terminology Criteria for Adverse Events version 4.0 will be used to grade toxicities during the trial. DLTs are defined as any of the following events occurring during and for the first 12 weeks after completing pleural IMRT |
Countries
United States
Outcome results
None listed