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

NCT00571298 | Completed Phase 1 DMC

• 1 other identifier: 07-091
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malignant Pleural Mesothelioma

Keywords

Extrapleural pneumonectomy; Pleurectomy Decortication; Mesothelioma; cisplatin; gemcitabine; amifostine; sodium thiosulfate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity.

  2 years

• To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way.

  2 years

Study Arms (3)

Extrapleural pneumonectomy (EPP)

EXPERIMENTAL

This is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate

Procedure: Extrapleural pneumonectomy (EPP); Drug: Cisplatin; Drug: gemcitabine; Drug: amifostine; Drug: sodium thiosulfate

Pleurectomy/Decortication (P/DC)

EXPERIMENTAL

This is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate

Drug: Cisplatin; Drug: gemcitabine; Drug: amifostine; Drug: sodium thiosulfate; Procedure: Pleurectomy/Decortication

Tumor Debulking (TD)

EXPERIMENTAL

This is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate

Drug: Cisplatin; Drug: gemcitabine; Drug: amifostine; Drug: sodium thiosulfate

Interventions

Extrapleural pneumonectomy (EPP) PROCEDURE

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)

Extrapleural pneumonectomy (EPP)

Cisplatin DRUG

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

Also known as: Platinol

Extrapleural pneumonectomy (EPP); Pleurectomy/Decortication (P/DC); Tumor Debulking (TD)

gemcitabine DRUG

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

Also known as: Gemzar

Extrapleural pneumonectomy (EPP); Pleurectomy/Decortication (P/DC); Tumor Debulking (TD)

amifostine DRUG

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

Extrapleural pneumonectomy (EPP); Pleurectomy/Decortication (P/DC); Tumor Debulking (TD)

sodium thiosulfate DRUG

Given intravenously immediately at the end of perfusion chemotherapy

Extrapleural pneumonectomy (EPP); Pleurectomy/Decortication (P/DC); Tumor Debulking (TD)

Pleurectomy/Decortication PROCEDURE

Resection of the lining of the lung (pleura), while the lung remains intact.

Pleurectomy/Decortication (P/DC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Dana-Farber Cancer Institute: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Links

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

MeSH Terms

Conditions

Mesothelioma, Malignant; Mesothelioma

Interventions

Cisplatin; Gemcitabine; Amifostine; sodium thiosulfate; Cerebral Decortication

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Organothiophosphates; Organophosphates; Organophosphorus Compounds; Organic Chemicals; Organothiophosphorus Compounds; Sulfur Compounds; Neurosurgical Procedures; Surgical Procedures, Operative

Study Officials

• Raphael Bueno, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 10, 2007
• First Posted: December 11, 2007
• Study Start: November 1, 2007
• Primary Completion: November 1, 2011
• Study Completion: June 1, 2015
• Last Updated: January 23, 2017

Record last verified: 2017-01

Locations

US (1)