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Taipei Medical University-Wan Fang Hospital
TITLE: Examples
Mechanisms of Resistance to Targeted Therapy with Imatinib in Patients with Leukemia
or
Breast Cancer Tissue and Clinical Data Repository for Identifying Molecular Markers of
Clinical Outcome
Principal Investigator:
Name
Address or Institution
Telephone
Co-Investigators:
Name
Address or Institution
Telephone
Statistician:
(if applicable)
Name
Address or Institution
Telephone
Data Manager/:
Study Coordinator
Name
Address or Institution
Telephone
Initial Protocol Date:
month/day/year
Protocol Revision Dates:
month/day/year
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TABLE OF CONTENTS
1. OBJECTIVES
2. BACKGROUND
Study Disease
Rationale
3. PATIENT or TISSUE SAMPLE SELECTION
Eligibility Criteria
4. METHODS
Source and Retention of Samples
Clinical Data Collection
Minimization of Risk and Protection of Confidentiality
5. LABORATORY PROCEDURES
6. STATISTICAL CONSIDERATIONS
Sample Size and Power
Methods
7. ETHICAL AND REGULATORY REQUIREMENTS
Protocol Review
Informed Consent
OHSU Cancer Institute Data and Safety Monitoring Plan
Inclusion of Women, Minorities and Children
8. REFERENCES
APPENDIX A
Data Collection Forms
APPENDIX B
Informed Consent Form
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1. OBJECTIVES
Insert primary protocol objectives.
Insert secondary protocol objectives, if pertinent.
For example:
1.1
To evaluate various tyrosine kinases for evidence of genomic and biochemical
activation.
1.2
To test the effect of small molecule kinase inhibitors on the activation of wildtype and mutant tyrosine kinases.
1.3
To correlate tumor genotype and signaling abnormalities with clinical response to
kinase inhibitors
1.4
Analysis of laboratory findings in relationship to patient demographics and clinical
course.
2. BACKGROUND
Study Disease
Provide background information on the study disease.
Rationale
Provide the background and rationale for evaluating this tissue in this way.
For example:
Tyrosine kinases are expressed by many human cancers.1,2 These enzymes are attractive
targets for the development of anticancer drugs because they can be inhibited by small
molecule compounds that have excellent potency and selectivity.3 The utility of this approach
has been highlighted by the success of Imatinib mesylate (Gleevec) in the treatment of
Chronic Myelogenous Leukemia and Gastrointestinal stromal tumors (GISTs).4-7 Expression
of tyrosine kinases is ubiquitous in both cancers and normal tissues. Therefore, the efficacy
of a kinase inhibitor is dependent on two critical factors: 1) the degree to which the target
kinase is activated in a particular cancer, and 2) the degree to which the growth and survival
of the cancer cells is dependent on the activated target kinase.1,2
Gastrointestinal stromal tumors provide an excellent example of this principle. KIT tyrosine
kinase is detectable by immunohistochemistry in a wide variety of cancers and normal
tissues, but mutations of the KIT gene that yield constitutively active KIT kinase are found in
only a small subset of tumors (Heinrich & Corless, unpublished results).8More than 85% of
GISTs harbor such activating mutations4,8-10 and, correspondingly, phosphorylation of KIT
kinase (a marker of activation) was recently demonstrated in 100% of fresh-frozen GIST
specimens analyzed.11 Such phosphorylation of KIT is rarely observed in other cancer
specimens (J. Fletcher, unpublished results). Recent success in the treatment of advanced
malignant GISTs with Imatinib mesylate is thought to reflect an important role of KIT
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activation in the growth and/or survival of GIST tumor cells.4,7 The observation that
treatment results with Imatinib mesylate are significantly better in tumors with evidence of
mutational activation of KIT than tumors with no KIT mutation further supports this view.8
Thus, in the case of GISTs, testing of clinical specimens for genomic mutations resulting in
tyrosine kinase activation will be useful in determining which patients are most likely to
respond to a tyrosine kinase inhibitor.
3. PATIENT or TISSUE SAMPLE SELECTION
Eligibility Criteria
For example
3.1
Patients must have histologically or cytologically confirmed…
3.2
Patients must have been treated with…
3.3
Tumor samples previously collected by…
3.4
De-identified tissue samples from…
3.5
Signed consent
4. METHODS
Source and Retention of Samples
Example
Study samples will be collected at the time of each scheduled blood draw and bone marrow
procedure for usual medical care. After adequate amounts have been obtained for clinical care, an
additional one to two teaspoon of blood and one teaspoon of bone marrow will be collected for
this study. The subject will be reminded that prior to or during each procedure they may decide
not to have the additional sample amount taken.
Or
De-identified tissue samples will be obtained from the research repository………
A specimen log will be maintained for all specimens received. Information documented on the
specimen log will include: all pertinent unique specimen identifier numbers, specimen type,
source, date received, date tested and date of final disposition. Add study specific information as
needed.
Clinical Data Collection
Example
The subject’s medical record will be reviewed for demographics, past history and course of
disease including clinical laboratory test results. Information will be stored in a passwordprotected database. Only the investigators, study coordinator and research assistant are given the
password. The Mechanisms of Imatinib Resistance database is stored on a network drive with
password protection and firewalls. Subject’s clinical laboratory results, research laboratory
results and clinical information will be entered into the database either manually or via electronic
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data feeds from the laboratory information systems which are password-protected and secure.
The database will include the subject’s name and medical record number in order to both allow
subsequent “accuracy checks” of the data and add future results from the same patient to the
appropriate database record. When a data set from the database is used for analysis or
publication, the data set will be locked and de-identified.
Or
Staging, treatment and clinical outcome data will be collected from Tumor Registries.
Or
Clinical information will be obtained through patient interview and questionnaire. Needs specific
detail.
Minimization of Risk and Protection of Confidentiality
Samples are provided in a way that does not link them to an individual.
Or
The subject’s de-identified data may be linked back to the name and medical record number by a
single master list accessible by the investigator.
5. LABORATORY PROCEDURES
Example:
Analysis of tissues will include identification of bio-markers by Western blotting techniques.
Control and extraction procedures include…
Tissue samples will be analyzed for specific gene expression by DNA microarray analysis…
6. STATISTICAL CONSIDERATIONS
This section should be developed in coordination with the biostatistician at ….
Sample Size and Power
Methods
Examples: Descriptive, Kaplan Meier survival estimates and Cox multivariate analysis.
7. ETHICAL AND REGULATORY REQUIREMENTS
Protocol Review
The protocol must be reviewed and approved in writing by the Institutional Review Board (IRB)
prior to any patient being registered or tissue being collected on this study.
Informed Consent
Written informed consent will be obtained from all patients, or the legally authorized
representative of the patient, participating in this trial, as stated in the Informed Consent section
of the case of DoH Regulations. If a patient’s signature cannot be obtained, and for all patient’s
under the age of 20, the investigator must ensure that the informed consent is signed by the
patient’s legally authorized representative. Documentation of the consent process and a copy of
the signed consent shall be maintained in the research record and patient’s medical record.
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Or
This protocol meets the criteria for waiver of informed consent and waiver of authorization.
Changes to Protocol
Any modification of this protocol must be documented in the form of a protocol revision or
amendment signed by the principal investigator and approved by the WFCRC and IRB, before
the revision or amendment may be implemented.
Maintenance of Records
Regulatory records and subject or tissue logs must be kept. If the investigator relocates or for any
reason withdraws from the study, the study records must be transferred to an agreed upon
designee, such as another institution, another investigator, or to the WF Clinical Research
Management.
Data and Safety Monitoring Plan
Who is responsible for conducting Quality Assurance audits on CI approved protocols. Please
provide the data and safety monitoring plan.
8.
REFERENCES
Provide the citations for all publications referenced in the text.
APPENDIX A
Data Collection Forms
APPENDIX B
Informed Consent Form
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