Integrated Research Program Builds Knowledge, Enhances Clinical Care for Mesothelioma
Clinical Research:
Clinical research that is conducted on human beings usually takes place in a hospital or clinical setting, builds upon the knowledge learned through applied and basic research and takes shape in treatments and drugs that directly improve human healthcare.
An integrated research endeavor including epidemiologic, basic, preclinical, and clinical research is a key component of the International Mesothelioma Program (IMP). Under the leadership of IMP Director David J. Sugarbaker, MD, experts from four Boston-area institutions bring together a long history of interest in mesothelioma as well as international reputations in epidemiology, prevention, and clinical care of cancer. Together they form a unique collaboration focused on better understanding the biologic basis of mesothelioma and improving survival and quality of life for patients with the disease.
The research program is designed to answer a range of questions about mesothelioma, all intended to contribute to the development of better therapies and improved outcomes for patients. What are the environmental factors contributing to the development of mesothelioma? What genetic factors predispose an individual to respond to environmental contamination by developing mesothelioma? Are there identifiable molecular markers that may aid in diagnosing, establishing the prognosis for, and identifying the most effective therapies for mesothelioma? How can therapy be tailored to address the specific needs of each individual patient? What innovative treatments will extend survival and improve quality of life for patients?
The major research initiatives that form the backbone of the research program emerged from years of discussion among researchers and clinicians from Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard School of Public Health, and Massachusetts General Hospital. Their strategic approach was to build an integrated, multidisciplinary research program capitalizing on the synergy of experts from many disciplines working in partnership to further the understanding of and pioneer new treatments for mesothelioma. IMP leaders expect that shared access to patients, clinical samples, and central databases will enhance the power of the data and accelerate the pace of research progress.
The epidemiology projects focus on identifying asbestos and other fibers associated with mesothelioma, discovering genetic risk factors that may predispose individual patients to develop mesothelioma, and understanding the processes by which asbestos is transported in the body with a goal of finding ways to interrupt the development of the disease.
The basic science and preclinical projects seek to contribute to the understanding of the biology of mesothelioma and to discover and validate molecular markers that may be useful in diagnosing, establishing a prognosis for, and treating mesothelioma.
Surgery Clincal Trials
Clinical Research Group
The clinical project aims to identify and validate new therapeutic strategies, including novel medications and innovative procedures that will extend survival and enhance quality of life for mesothelioma patients everywhere.
Being in the forefront of mesothelioma research means not only that IMP researchers contribute to the understanding of mesothelioma but also that IMP clinicians rapidly can translate to clinical practice those discoveries that that can benefit patients.
David J. Sugarbaker has conducted multimodality clinical treatment trials, involving surgical resection by extrapleural pneumonectomy (EPP) or pleurectomy combined with intrathoracic/intraperitoneal heated chemotherapy. Three surgical clinical trials are currently opened and accruing patients: a Phase II (EPP) clinical trial, involving extrapleural pneumonectomy (removal of the lung and lining of the chest cavity) and heated chemotherapy applied to the chest and abdominal cavities during the operation, followed by chemotherapy and radiation; a Phase II (randomized Pleurectomy) clinical trial, involving pleurectomy (removal of the lining of the lung and chest cavity while preserving the lung) and heated chemotherapy during the operation followed by chemotherapy; and a Phase II ‘neoadjuvant’ trial involving treatment with the chemotherapy drugs ALIMTA and cisplatin, followed by an EPP, followed by radiation.
Because recurrence of the disease generally occurs on the same side where the tumor was removed, it was logical to pursue therapy to control this recurrence. Our approach was to pursue intraoperative, intracavitary, heated chemotherapy as a way to optimize control of local disease spread. We are conducting two trials utilizing intraoperative, intracavitary, heated chemotherapy but differing according the extent of surgical resection that the patient can tolerate. Extrapleural pneumonectomy represents the optimal procedure to reduce tumor burden to the microscopic level. A second trial, utilizing pleurectomy, is offered to patients who lack the cardiopulmonary reserve to undergo a pneumonectomy.
1. Phase I Feasibility study of Extrapleural Pneumonectomy (EPP) or Pleurectomy Decortication (PDC) with Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin and Gemcitabine with Intravenous Amifostine and Sodium Thiosulfate Cytoprotection for Patients with Resectable Malignant Pleural Mesothelioma (Protocol 07-091) is open and accruing patients. This study involves a cytoreductive surgery (EPP or PDC)followed by heated chemotherapy (cisplatin and gemcitabine) administered in the operating room and put into the chest and abdomen for one hour after the surgical removal of the cancer. The goal in this study is tosurgically remove the mesothelioma (macroscopic complete resection) and to use the chemotherapy to contain the local spread of the disease. Extrapleural pneumonectomy represents the optimal procedure to reduce tumor burden to the microscopic level. 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 the chemotherapy.For more information please click here.
2. A Phase II Feasibility Study of Pleurectomy/Decortication with Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin with Sodium Thiosulfate Followed by Adjuvant Cisplatin/ALIMTA is open and accruing patients.
3. Phase II Feasibility study of Extrapleural Pneumonectomy (EPP) with Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin with Sodium Thiosulfate (Protocol 03-302) is not recruting patients. This study involved a treatment consisting of EPP (removal of both the lung and its lining) followed by heated chemotherapy (cisplatin) administered in the operating room and put into the chest and abdomen for one hour after the surgical removal of the cancer. The goal in this studywas to use EPP to surgically remove the mesothelioma and to use the chemotherapy to contain the local spread of the disease. This study was published this year (2009, Journal of Thoracic and Cardiovascular Surgery (JTCVS).
Back to the Top
The Clinical Research teamoversees screening, consenting, enrolling, and follow-up and data analysis of Mesothelioma patients on clinical trials. The team is made up of a Medical Director of the Clinical Research, fourClinical Research Associates (CRA), and a programmer/data analyst.
The Clinical research team’s role in the program is to screen all patients that come to the Thoracic Surgery Clinic (approximately 300 patients per week) to determine if they are eligible to enroll or were previously enrolled in Institutional Review Board-approved mesothelioma protocols. CRAs consent patients to non-treatment protocols and work with physicians to facilitate consent of patients to treatment studies. Once patients are consented and enrolled in studies, the CRAs oversee that all procedures are performed and documented per regulatory requirements, and update databases with study specific information (enrollment, procedures, pathology results, survival and treatment information). In addition, CRAs maintain on-going communication with the IRB (either Dana Farber and/or Partners Health Care) for reporting adverse events, submitting protocol changes and annual Continuing Reviews of all protocols. Currently the BWH Thoracic surgery has 9 active IRB approved protocols which are Mesothelioma-related.
Currently there are two open treatment clinical trials: protocol 04-063 and protocol 07-091. Both have a heated intraoperative chemotherapy component. . The 07-091 Phase I study of two chemotherapeutic agents given during extra-pleural pneumonectomy surgery (one arm) or pleurectomy/decortication (second arm) following cytoreduction of visible mesothelioma disease, required IRB approval by the DFCI and was also submitted and approved by the FDA as an Investigational New Drug study (IND), with the IND held by Dr. Sugarbaker. Since start-up, 302 mesothelioma patients have been screened for study participation, 60 have been enrolled (49 enrolled for pneumonectomy, 14 enrolled for pleurectomy) and underwent the protocol operation with chemotherapy. CRAs document treatment specifics and adverse events in an electronic data database that is maintained by the DFCI. During the surgeries, CRAs manage the collection of tissue and blood specimens. Specimens are transported to a tissue bank, where they are prepared and frozen for pathologic and pharmacokinetic research.
All patients going for debulking surgery are also approached for consent of banking of blood and tissue for genetic analysis (688 mesothelioma patients have been consented to date), and for consent to take urine specimens for identification of potential renal injury markers. (More than 100 mesothelioma patients have been consented to this study.) All new Mesothelioma patients and all returning patients who are recurrence-free for at least a year are eligible to participate in a Quality Of Life protocol, which has the patients complete multiple questionnaires over the course of 36 weeks (99 patients have been enrolled since protocol start-up).
A new responsibility for the CRAs is overseeing a large epidemiology study, which has been transferred to the Thoracic Surgery research program. The goal of the study is to consent all Mesothelioma patients seen in the clinic to an extensive lifestyle and history questionnaire and to collect tissue and blood samples. Nearly 389 patients have been enrolled since the protocol was opened.
The Medical Director of Clinical Research, Dr. Tamara Tilleman, oversees current projects, works with physicians to identify relevant clinical research studies and shepherds new publications (which includes on-going analysis of closed research studies). She assists in writing new protocols using evidence based medicine and the current research knowledge obtained by the IMP program at BWH. Thoracic surgery protocols, including Mesothelioma protocols, are written according to state and federal regulations while ensuring patient safety. The director also presents at a weekly New Patient Mesothelioma Class, which provides patients and their families with an overview of the multiple research studies available and principles of clinical research. Dr. Tilleman also oversees the updated information on the IMP website (http://www.brighamandwomens.org/mesothelioma) and is operating booths at annual meetings. This year, the IMP program had a booth at three yearly meetings; Massachusetts Thoracic Society, April 2009, the American Thoracic Society, San Diego May 2009, and the American College of Chest Physicians, San Diego, November 2009. We met with 398 pulmonologists, 195 of them are practicing outside the United States. From those meetings, we have started several clinical and research collaborations.
The Data Base Manager/Analyst assists with database design and update of large blocks of data pulled directly from the patient’s medical records via the hospital Research Patient Data Repository. During 2009, the IMP Patient Data Registry (over 2200 mesothlioma patients) was redesigned by the Data Base Manager/Analyst to allow easier electronic data capture and retrieval for research purposes. We used a relational database management system (MySQL,) and developed a professional entity/relationship database schema that allows us to connect the patient to related data (like pathology or staging) and helps us conform to IRB and HIPPA regulations. In addition, the data analyst works with the IMP team to analyze data and runs reports on all aspects of current and past protocol results.
In the last year, 22 abstracts and manuscripts were generated from the IMP Patient Data Registry (http://www.brighamandwomens.org/mesothelioma/Publications_Updated.aspx?subID=submenu4)
To view a comprehensive listing of clinical trials that are offered worldwide, please click hereand search "pleural mesothelioma".
Back to the Top
Send Feedback to: 
