NCT00571298

Extrapleural Pneumonectomy /Pleurectomy Decortication, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma

A Phase I Trial of Extrapleural Pneumonectomy/Pleurectomy Decortication, Intrathoracic/Intraperitoneal Hyperthermic (IOHC) Cisplatin and Gemcitabine With Intravenous Amifostine and Sodium Thiosulfate Cytoprotection for Patients With Resectable Malignant Pleural Mesothelioma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 141 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: After removal of visible cancer in the chest, chemotherapy drugs are used to kill or stop tumor cells from dividing, so that they stop growing or/and die. Cisplatin is currently used safely as in intra-operative treatment for malignant pleural mesothelioma. This study is aimed to determine if the addition of gemcitabine as a second intracavitary chemotherapy can be accomplished safely. PURPOSE: This is a Phase I trial to study the efficacy of combination chemotherapy consisting of gemcitabine and cisplatin administered in the operating room and put into the chest and abdomen for one hour. We are also looking at the effects of heating the chemotherapy to a temperature of 42 degrees Celsius and the effect of cytoprotection agents: amifostine and sodium thiosulfate to counteract potential side effects of chemotherapy.

Detailed description

* This is a dose escalation study of gemcitabine with a fixed dose of cisplatin * Patients will undergo cytoreductive surgery, which entails the removal of the inner and outer lining of the lung (pleurectomy/decortication) with or without the lung itself (extrapleural pneumonectomy), including the lining overlying the pericardium and diaphragm. Resection of the pericardium and diaphragm are occasionally necessary to remove all visable tumor. This surgery is part of standard care for malignant pleural mesothelioma. * After surgery, a one hour lavage with heated cisplatin and or gemcitabine will be administered to the hemithorax (and abdominal regions if the diaphragm is no longer present). * Patients will remain hospitalized until they have recovered from surgery (usually 7-14 days). * Patients will return to the hospital during the first month after their surgery to be evaluated by the medical staff. * Dose escalation: 1) Three patients will be treated at the first dose level of gemcitabine. Labs will be monitored on a weekly basis, including a CBC, Chem-7, and LFT's. In the absence of developing dose-limiting toxicity (DLT) among the first 3 patients treated, dosages can be escalated. DLT will be defined as any grade 3 or higher renal toxicity, thrombocytopenia or other grade 3 toxicity not related to surgery 2) If none of these 3 patients have any toxicity, we will proceed to the next level of gemcitabine. 3) If DLT occurs in 1 of 3 patients at a given dose level, then 3 additional patients are added at that dose (for a total of 6 at this level)If no DLT occurs, we will proceed to the next level of gemcitabine. If DLT occurs in another patient, this dose is considered the maximum tolerated dose (MTD). 4) At any dose, 3 cases of DLT lead to discontinuation of recruitment at that dose and enrollment of 3 additional patients at a lower dose.

Conditions

• Malignant Pleural Mesothelioma

Interventions

Type	Name	Description
PROCEDURE	Extrapleural pneumonectomy (EPP)	Resection of the lung, the lining of the lung (pleura), the covering of the heart (pericardium), and the muscle that separates the chest and abdomen (diaphragm)
DRUG	Cisplatin	Given after the tumor is removed as a bath (perfusion) for one-hour
DRUG	gemcitabine	Given after the tumor is removed as a bath (perfusion) for one-hour
DRUG	amifostine	Given intravenously before perfusion chemotherapy and then 2 hours after the first dose
DRUG	sodium thiosulfate	Given intravenously immediately at the end of perfusion chemotherapy
PROCEDURE	Pleurectomy/Decortication	Resection of the lining of the lung (pleura), while the lung remains intact.

Timeline

• Start date: 2007-11-01
• Primary completion: 2011-11-01
• Completion: 2015-06-01
• First posted: 2007-12-11
• Last updated: 2017-01-23

Locations

1 site across 1 country: United States