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

Sponsor:	Brigham and Women's Hospital
Collaborator:	Dana-Farber Cancer Institute
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00571298

Purpose

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.

Condition	Intervention	Phase
Malignant Pleural Mesothelioma	Procedure: Extrapleural pneumonectomy (EPP), Pleurectomy/Decortication Drug: cisplatin Drug: gemcitabine Drug: amifostine Drug: sodium thiosulfate	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Fever Mesothelioma

Drug Information available for: Sodium thiosulfate Cisplatin Amifostine Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

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. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	November 2007
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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)

Given after the tumor is removed as a bath (perfusion) for one-hour

Other Name: Platinol

Given after the tumor is removed as a bath (perfusion) for one-hour

Other Name: Gemzar

Given intravenously before perfusion chemotherapy and then 2 hours after the first dose

Given intravenously immediately at the end of perfusion 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571298

Contacts

Contact: David Sugarbaker, M.D.	617-732-5004	dsugarbaker@partners.org
Contact: Tamara Tilleman, M.D, PhD	617-732-5079	ttilleman@partners.org

Locations

United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: David J Sugarbaker, MD

Sponsors and Collaborators

Brigham and Women's Hospital

Dana-Farber Cancer Institute

Investigators

Principal Investigator:

David J Sugarbaker, MD

Brigham and Women's Hospital

More Information

Additional Information:

Brigham and Women's Hospital, Mesothelioma and International Mesothelioma Program This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	David J. Sugarbaker, MD, Brigham and Women's Hospital International Mesothelioma Program, Division of Thoracic Surgery
ClinicalTrials.gov Identifier:	NCT00571298 History of Changes
Other Study ID Numbers:	07-091
Study First Received:	December 10, 2007
Last Updated:	October 30, 2009
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:

Extrapleural pneumonectomy
Pleurectomy Decortication
Mesothelioma
cisplatin

gemcitabine
amifostine
sodium thiosulfate

Additional relevant MeSH terms:

Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Gemcitabine
Cisplatin
Amifostine
Sodium thiosulfate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

Radiation-Protective Agents
Protective Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Antioxidants
Antitubercular Agents
Anti-Bacterial Agents
Chelating Agents
Antidotes

ClinicalTrials.gov processed this record on May 22, 2012