A Phase I Study of Concurrent Pemetrexed/Cisplatin With Pleural Intensity Modulated Radiation Therapy for Patients With Unresectable Malignant Pleural Mesothelioma
Overview
- Phase
- Phase 1
- Intervention
- Pemetrexed/Cisplatin
- Conditions
- Malignant Pleural Mesothelioma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Locations
- 6
- Primary Endpoint
- Dose limiting toxicities (DLT)
- Status
- Withdrawn
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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 exclusion criteria will be excluded from the MRI portion only:
- •Metallic implant, e.g. pacemaker, defibrillator
Arms & Interventions
pemetrexed/cisplatin with pleural IMRT
This is a single institution phase I study of pemetrexed/cisplatin given concurrently with pleural intensity modulated radiation therapy (IMRT) in patients with unresectable malignant pleural mesothelioma (MPM). All patients will receive pleural intensity modulated radiation therapy (IMRT). Patients will be enrolled in cohorts of 3-6 at each dose level of pemetrexed/cisplatin, and dose escalation will proceed in a standard 3+3 fashion until the maximum tolerated dose (MTD) is identified.
Intervention: Pemetrexed/Cisplatin
pemetrexed/cisplatin with pleural IMRT
This is a single institution phase I study of pemetrexed/cisplatin given concurrently with pleural intensity modulated radiation therapy (IMRT) in patients with unresectable malignant pleural mesothelioma (MPM). All patients will receive pleural intensity modulated radiation therapy (IMRT). Patients will be enrolled in cohorts of 3-6 at each dose level of pemetrexed/cisplatin, and dose escalation will proceed in a standard 3+3 fashion until the maximum tolerated dose (MTD) is identified.
Intervention: Pleural Intensity Modulated Radiation Therapy
pemetrexed/cisplatin with pleural IMRT
This is a single institution phase I study of pemetrexed/cisplatin given concurrently with pleural intensity modulated radiation therapy (IMRT) in patients with unresectable malignant pleural mesothelioma (MPM). All patients will receive pleural intensity modulated radiation therapy (IMRT). Patients will be enrolled in cohorts of 3-6 at each dose level of pemetrexed/cisplatin, and dose escalation will proceed in a standard 3+3 fashion until the maximum tolerated dose (MTD) is identified.
Intervention: MRI
Outcomes
Primary Outcomes
Dose limiting toxicities (DLT)
Time Frame: 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