Verified by Dana-Farber Cancer Institute, January 2009
Brigham and Women's Hospital
Dana-Farber Cancer Institute
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| Dana-Farber Cancer Institute |
| NCT00571298 |
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.
Malignant Pleural Mesothelioma
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Procedure: Extrapleural pneumonectomy (EPP)
Drug: cisplatin
Drug: gemcitabine
Drug: amifostine
Drug: sodium thiosulfate
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Phase I
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ChemIDplus related topics:
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Cisplatin
Amifostine
Sodium hyposulfite
Trichloroethylene
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| Study Type: |
Interventional |
| Study Design: |
Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety Study |
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| Official Title: |
A Phase I Trial of Extrapleural Pneumonectomy, Intrathoracic/Intraperitoneal Hyperthermic (IOHC) Cisplatin and Gemcitabine With Intravenous Amifostine and Sodium Thiosulfate Cytoprotection for Patients With Resectable Malignant Pleural Mesothelioma |
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:
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
- This is a dose escalation study of gemcitabine with a fixed dose of cisplatin
- Patients will undergo surgery with Extrapleural Pneumonectomy, which entails the removal of the inner and outer lining of the lung (pleura) and the lung itself, 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.
| Ages Eligible for Study: |
18 Years and older |
| Genders Eligible for Study: |
Both |
| Accepts Healthy Volunteers: |
No |
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 Extrapleural Pneumonectomy (EPP)
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00571298
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| Brigham and Women's Hospital |
| Boston, Massachusetts, United States, 02115 |
| Principal Investigator: David J Sugarbaker, MD |
Brigham and Women's Hospital
Dana-Farber Cancer Institute
| Principal Investigator: |
David J Sugarbaker, MD |
Brigham and Women's Hospital |
| Responsible Party: |
Brigham and Women's Hospital International Mesothelioma Program, Division of Thoracic Surgery ( David J. Sugarbaker, MD ) |
| Study ID Numbers: |
07-091 |
| Study First Received: |
December 10, 2007 |
| Last Updated: |
January 6, 2009 |
| ClinicalTrials.gov Identifier: |
NCT00571298
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| Health Authority: |
United States: Institutional Review Board |
Keywords provided by Dana-Farber Cancer Institute:
Extrapleural pneumonectomy
cisplatin
gemcitabine
amifostine
sodium thiosulfate
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Study placed in the following topic categories:
Fever
Amifostine
Cisplatin
Sodium thiosulfate
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Mesothelioma
Gemcitabine
Adenoma
Neoplasms, Glandular and Epithelial
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Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Radiation-Protective Agents
Antioxidants
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Neoplasms, Mesothelial
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
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Immunosuppressive Agents
Antiviral Agents
Protective Agents
Pharmacologic Actions
Anti-Bacterial Agents
Neoplasms
Radiation-Sensitizing Agents
Therapeutic Uses
Chelating Agents
Antitubercular Agents
Antidotes
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ClinicalTrials.gov processed this record on January 22, 2009
Source: www.ClinicalTrials.gov
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