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

Malignant Pleural Mesothelioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00571298
• Other study ID #: 07-091
• Status: Completed
• Phase: Phase 1
• First received: December 10, 2007
• Last updated: January 19, 2017
• Start date: November 2007
• Est. completion date: June 2015

Study information

• Verified date: January 2017
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: June 2015
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically-proven diagnosis of stages I to III malignant mesothelioma of the pleura and negative mediastinal N2 lymph nodes (Malignancy is confined to the affected hemithorax)

• Adequate organ function including the following: adequate cardiac function, pulmonary function, renal and hepatic function and bone marrow reserve

• Adequate overall physical activity

• Surgical candidate for cytoreductive surgery

Exclusion Criteria:

• Extended disease outside the ipsilateral hemithorax as proven histologically, radiologically and/or intraoperatively

• Have received chemotherapy and or radiation therapy within the last 3 years at the time of study entry

• Serious concomitant systemic disorders

• Second active primary malignancy (to exclude non- melanoma skin cancer)

• Pregnancy at the time of the operation

• Psychiatric or addictive disorder which would preclude obtaining informed consent

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma
• Mesothelioma

Intervention

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
• gemcitabine
Given after the tumor is removed as a bath (perfusion) for one-hour
• amifostine
Given intravenously before perfusion chemotherapy and then 2 hours after the first dose
• 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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To establish the maximally tolerated dose (MTD) of intraoperative Intrathoracic/Intraperitoneal hyperthermic gemcitabine and cisplatin combination modulated by amifostine and sodium thiosulfate in patients with malignant pleural mesothelioma.		2 years
Secondary	To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity.		2 years
Secondary	To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way.		2 years

External Links

•   Brigham and Women's Hospital, Mesothelioma and International Mesothelioma Program