THE MESOTHELIOMA APPLIED RESEARCH FOUNDATION
CLINICAL RESEARCH PROJECT
COLLECTION OF CLINICAL DATA, SERUM, BLOOD
CELLS, AND TISSUE SAMPLES FROM PATIENTS WITH
BIOPSY-PROVEN OR SUSPECTED MESOTHELIOMAS
Objectives
Primary Objective. The primary objective
of this study is to collect clinical data, serum, blood
cells, and tissue samples from patients with mesothelioma
for use in Mesothelioma National Data/Tissue Bank
initiated in cooperation with UCLA and the Mesothelioma
Applied Research Foundation (MARF).
Secondary Objective. The secondary objective is to act as
a tissue bank to provide material for future research for
the investigators, MARF physicians, and collaborators.
Background and Significance
Background. . Mesothelioma is a deadly
malignancy that affects an unknown number of people in
the U.S. and throughout the world each year. Due to the
relatively small numbers involved compared to other major
cancers, mesothelioma has been essentially ignored for
nearly 40 years. Patients are treated at a variety of
centers throughout this country with poorly documented
results. It is imperative that a centralized databank be
established in order to understand the natural history of
the disease and the outcomes from treatments currently
being used as well as those developed in the future, to
better evaluate the benefits of the various current
treatment approaches, and to best evaluate and prove
effectiveness of future novel therapies. In addition, a
parallel tissue bank would be invaluable in the analysis
of tumors for more rational treatment planning in the
future. The Mesothelioma Applied Research Foundation
(MARF), with its national group of committed mesothelioma
physicians and researchers, has teamed up with UCLA to
initiate this project as a high priority.
Significance. Ongoing as well as future
research in patients with mesothelioma within the medical
community depend on the availability of serum, blood
cells, and tissue samples from patients with malignant
disease. Specifically, current and planned research
projects often require serial serum and blood cell
samples from cancer patients throughout the course of
their disease (to correlate novel experimental results
with developments in the clinical course of the
patient's disease) as well as cancer tissue obtained
from these patients at the time of planned surgery. With
appropriate access to these serum, blood cell, and tissue
samples, research projects within the medical community
will be able to identify novel methods of cancer
treatment using the immune system and possibly new
substances to block biologic pathways in cancer cells.
Collaboration between the Mesothelioma Applied Research
Foundation (MARF) and a number of institutions has
provided a unique ability to establish a national data
and tissue bank for use in mesothelioma research.
Subject Population
Eligibility Requirements. All patients
with biopsy-proven or suspected malignant mesothelioma
are eligible. All patients who are seen by thoracic
surgeons within the Department of Surgery, medical
oncologists within the Department of Medicine, and
radiation oncologists within the Department of Radiation
Oncology will be evaluated by their attending physician
for their suitability for serum, blood cell, and tissue
collection.
Patient Accrual Goals. In order to
maximize the utility of the information and tissue
collected, it is estimated that approximately 5000
patients with pathologically documented malignancies will
be needed over the next 5 years. Therefore, an accrual of
approximately 1000 patients/year is anticipated. This
will be obtained through the collaboration of multiple
centers throughout North America, including the
Mesothelioma Applied Research Foundation (MARF).
Design/Methodology
Patient Participation. All patients with
biopsy-proven or suspected malignant mesothelioma will
have clinical data and blood samples collected. In
addition, a sample of normal as well as malignant tissue
will be taken at the time of planned surgery. This
collection will in no way interfere with the adequate
pathologic evaluation of the specimen or in the health of
the patient. If there is any doubt as to the necessity
for all tissue to be pathologically reviewed, none will
be harvested. In addition, if the patient develops severe
anemia, particularly if blood transfusion is being
considered, no blood will be collected.
Procedures. The following procedures
will be performed as part of this protocol:
Data collection. At the time of
initial patient evaluation and/or during subsequent
patient encounters, medical records, including
presenting symptoms, radiologic data and images,
pathology, treatment records, and outcomes, will be
collected and entered into a national mesothelioma data
registry maintained at UCLA Medical Center in
cooperation with the Mesothelioma Applied Research
Foundation (MARF). All data will be sent by facsimile
to the data center at UCLA Medical Center and then
coded with a unique identification number as the sole
identifying information. All personal information (ie,
name, address [except state], social security number,
telephone number, and insurance information) will be
removed. A log that identifies the patients and their
identification numbers will be kept in a locked file
cabinet in the office of the principle investigator at
UCLA. The only people who will have access to the code
will be Dr. Robert Cameron and the data entry/study
nurse.
Blood collection. At the time of
initial patient evaluation and/or during subsequent
patient encounters, 100 cc of blood (approximately 3.3
oz or 4 tablespoons) will be drawn into tubes with
heparin anticoagulant. A maximum of twelve (12)
specimens will be obtained from each patient over no
less than 12 weeks. Tubes will be labeled wit the
patient's name, identifying information, and the
time and date of blood collection. These samples will
be transported to the Mesothelioma National Data/Tissue
Bank Laboratory (currently room 62-151 CHS at UCLA
Medical Center). The blood will then be centrifuged,
and the serum will be collected, frozen, and entered
into a computerized tissue bank. The peripheral blood
mononuclear cells also will be collected, washed,
cryopreserved, and stored.
Tissue collection. No tissue will be
removed from patients solely for use in this protocol.
However, if tissue is removed from patients in this
protocol during the normal course of treatment, a
portion of the excised malignant and/or normal tissue
may be separated from the main specimen by the surgeon
for storage in the National Mesothelioma Data/Tissue
Bank. The surgeon will work directly with the
pathologist to insure that removal of any tissue will
not compromise the accurate pathologic assessment of
the malignancy. Tissue samples will be transported to
the Mesothelioma National Data/Tissue Bank Laboratory
(currently room 62-151 CHS at UCLA Medical Center). The
tissue will then be processed for RNA, DNA, protein,
and whole cells (if available), frozen, and entered
into a computerized tissue bank.
Treatment Plan. Standard treatment for
individual malignancies will be followed at all times.
Patients admitted to this protocol will not be admitted
to protocols of experimental treatments unless they also
specifically meet the eligibility requirements and sign
informed consent for experimental protocols approved by
the Human Subjects Protection Committee at your treating
medical facilities. Due to participation in this study,
patients may be asked to participate in future studies.
Prior approval in the form of additional research
protocols, however, will be obtained from the Human
Subjects Protection Committee at your treating medical
facilities, and patients will be required to sign
separate informed consent forms for all such studies.
Risks. The risks of this protocol are
minimal and are limited to complications of phlebotomy,
such as discomfort from the needle stick, bruising, and
rarely infection; and loss of privacy. Standard sterile
technique will be used at all times in the collection of
blood specimens. In addition, research records will be
handled as carefully as possible to maintain patient
confidentiality in accordance with the Federal Privacy
Act. Upon arrival in the Mesothelioma National
Data/Tissue Bank Laboratory, all medical records and
specimens (serum, blood cells, and tissue samples) will
be coded and given a unique identification number.
Subsequently, the information and specimens will be
handled in a blinded fashion in all research procedures.
The identity of the patients will be permanently linked
to the specimens only by a confidential log that will be
maintained in a locked file by the principle investigator
at UCLA/MARF, Dr. Robert B. Cameron. This research will
be covered by an NIH-sponsored Certificate of
Confidentiality. The Certificate of Confidentiality will
cover a 5 year period. At the each 5 year period, either
the Certificate of Confidentiality will be renewed and
the protocol reapproved by the IRB or the confidential
log will be destroyed. It will be the responsibility of
the principal investigator to destroy the confidential
log if such renewals/approvals are not obtained.
Data Analysis
The anonymous data without any identifiers will be
available for researchers to analyze following approval
of a research proposal. The proposal will be reviewed by
a committee chaired by Dr. Cameron and consisting of
members of the MARF Scientific Advisory Board. This
process will occur through MARF as a "clinical"
research protocol. Each proposal will be required to
identify the data and tissues required and to justify the
uses of this data and tissue. The primary method of data
analysis will depend on the individual research study.
Since most studies will include small numbers of
specimens for analysis, it is anticipated that a
nonparametric method of data comparison often will be
used.
Benefits
There sill be no direct benefit to patients participating
in this study; however, it is hoped that the information
gained form this study will help in the immunologic
treatment of patients with thoracic malignancies in the
future..
Consent
An informed consent (see addendum) will be signed by all
patients entering this protocol. It will be obtained by
one of the investigators at the time of initial
outpatient consultation or upon inpatient admission for
surgery.
Investigators
MARF Principle Investigator. Dr. Robert
B. Cameron is a cardiothoracic surgeon and chief of
general thoracic surgery and thoracic oncology at UCLA
and the West Los Angeles VA Medical Center. He completed
his medical school education at UCLA School of Medicine
where he also completed his general surgery training. He
completed addition training fellowships in surgical
oncology at the National Cancer Institute under the
auspices of Dr. Steven A Rosenberg and in cardiothoracic
surgery at New York Hospital/Cornell Medical Center and
Memorial Sloan-Kettering Cancer Center under Drs. O.
Wayne Isom and Robert J. Ginsberg. He has extensive
experience in cancer research with over 40 publications
in this field.
MARF Executive Director. Chris Hahn
earned undergraduate degrees summa cum laude in
Philosophy and English, and is an Order of the Coif
graduate of the Boalt Hall School of Law, University of
California, Berkeley. His professional background
includes extensive involvement in nonprofit law and
administration as well as three years with the West Coast
law firm of Heller, Ehrman, White & McAuliffe, and
eight years with Seed, Mackall & Cole, one of the
preeminent business law firms in Santa Barbara. Chris is
a skilled communicator, organizer, problem solver, and
advocate. He has served MARF as Executive Director since
July, 2000.
UCLA Data Nurse. Rusela Bedrejo has over
10 years of nursing experience, including acute care (ICU
and Medical/Surgical Unit care), case management, and
utilization review. She will be solely responsible to the
data entry and with Dr. Cameron will maintain the
confidentiality of all patient information and specimens.
