Concurrent Pemetrexed/Cisplatin With Pleural Intensity Modulated Radiation Therapy for Patients With Unresectable Malignant Pleural Mesothelioma

Malignant Pleural Mesothelioma Clinical Trial

Official title:

A Phase I Study of Concurrent Pemetrexed/Cisplatin With Pleural Intensity Modulated Radiation Therapy for Patients With Unresectable Malignant Pleural Mesothelioma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02639767
• Other study ID #: 15-304
• Status: Withdrawn
• Phase: Phase 1
• First received: December 18, 2015
• Last updated: December 5, 2016
• Start date: December 2015

Study information

• Verified date: December 2016
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 exclusion criteria will be excluded from the MRI portion only:

• Metallic implant, e.g. pacemaker, defibrillator

• Unmanageable claustrophobia

• High risk for nephrogenic systemic fibrosis

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma
• Mesothelioma

Intervention

Drug:
• Pemetrexed/Cisplatin
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.

Radiation:
• Pleural 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.

Device:
• MRI
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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering at Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York
United States	Memoral Sloan Kettering Cancer Center at Phelps	Sleepy Hollow	New York
United States	Memorial Sloan Kettering West Harrison	West Harrison	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities (DLT)	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	up to 12 weeks	Yes

External Links

•   Memorial Sloan Kettering Cancer Center