OHSU Knight Cancer Institute

OHSU Knight Cancer Institute

Human Tissue Protocol
Template Instructions

The protocol template is a tool to facilitate protocol development for tissue studies that may or may not also collect clinical information. It is not intended to supercede the role of the Principal Investigator in the authoring and scientific development of the protocol, however some sections are required. This template contains sample and some required text for protocols submitted to OHSU Knight Cancer Institute.

• It is recommended that primary section headings in the protocol template be retained to facilitate review. If one is not appropriate for a given study, please go ahead and delete the unneeded section.

• Sample text may be modified as necessary to meet the scientific aims of the study.

• Protocol template instructions and samples are in italics. As you complete the information requested, delete the italicized text and any instructions.

For questions about protocol development contact:

Susan Aust, MSPH, CCRP

Protocol Development and Support Specialist

503 494-4108

For questions about protocol submission contact:

Kristin Hackney, MPHA, CCRP

Mail Code CH15R

503-494-6508

For protocol submission to OHSU Knight Cancer Institute, follow instructions on the submission checklist found at theKnight Clinical Trials Office site

Original Template 03/30/2005

Revised 7/07/2010

OregonHealth & ScienceUniversity

OHSU Knight Cancer Institute

IRB Protocol #:

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:Name

(If applicable)Address or Institution

Telephone

Data Manager/Name

Study Coordinator:Address or Institution

Telephone

Initial Protocol Date:month/day/year

Protocol Revision Dates:month/day/year

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 IRB Reporting of Unanticipated Problems and Adverse Events

OHSU Knight Cancer Institute Data and Safety Monitoring Plan

Inclusion of Women, Minorities and Children

8. REFERENCES

APPENDIX A

Data Collection Forms

APPENDIX B

Shipping Instructions

1.OBJECTIVES(required)

Insert primary protocol objectives.

Insert secondary protocol objectives, if pertinent.

For example:

1.1To evaluate various tyrosine kinases for evidence of genomic and biochemical activation.

1.2To test the effect of small molecule kinase inhibitors on the activation of wild-type 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(required)

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 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(required)

Eligibility Criteria

For example

3.1Patients must have histologically or cytologically confirmed…

3.2Patients must have been treated with…

3.3Tumor samples previously collected by…

3.4 De-identified tissue samples from…

3.5 Signed consent or waiver of HIPAA authorization

4.METHODS(required)

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 password-protected database. Only the investigators, study coordinator and research assistant are given
the password. The Mechanisms of Imatinib Resistance database is stored on an OHSU ITG supported shared 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 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 (required)

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 (required)

This section should be developed in coordination with the biostatistician at OHSU Knight Cancer Institute. Contact Dr. Motomi Mori 503-402-2871

Sample Size and Power

Methods

Examples: Descriptive, Kaplan Meier survival estimates and Cox multivariate analysis.

1. ETHICAL AND REGULATORY REQUIREMENTS(required)

Protocol Review(required)

The protocol must be reviewed and approved in writing by the OHSU Knight Cancer Institute (CI) Clinical Research Review Committee (CRRC) and OHSU Institutional Review Board (IRB) prior to any patient being registered or tissue being collected on this study.

Informed Consent(only if applicable)

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 Consentsection of the case of Federal Regulations, Title 21, Part 50. If a patient’s signature cannot be obtained, and for all patient’s under the age of 18, 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.

Or(only if applicable)

This protocol meets the criteria for waiver of informed consent and waiver of HIPAA authorization.

Changes to Protocol (required)

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 CRRC and IRB, before the revision or amendment may be implemented.

Maintenance of Records(required)

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 OHSU Knight Cancer Institute Clinical Research Management.

OHSU IRB Reporting of Unanticipated Problems and Adverse Events(only if applicable)

Unanticipated Problems (UP) and Adverse Events (AE) will be reported to IRB according to the policies, procedures and guidelines posted on the OHSU IRB web site

Fatal and life-threatening UP will be reported to OHSU IRB within 7 days of notification of the event. All other UP reports will be submitted to OHSU IRB no later than 15 days of occurrence or notification of the event. Copies of the report documents will be kept in the study regulatory binder.

UP and AE reports are submitted through OHSU e-IRB and will be reviewed by OHSU Knight Cancer Institute and IRB. Monthly accumulative reports will be reviewed by a DSMC Oncologist and forwarded to the CRRC.

OHSU Knight Cancer Institute Data and Safety Monitoring Plan(only if applicable)

OHSU Knight Cancer Institute (CI), CRM shared resource is responsible for ensuring that all member investigators and affiliate investigators conduct clinical research studies in compliance with local IRB standards, FDA regulations and NIH policies. The Data and Safety Monitoring Committee (DSMC) is responsible for conducting Quality Assurance audits on CI approved protocols according to the Data and Safety Monitoring Plan policies and procedures

The DSMC is responsible for conducting Quality Assurance audits on OHSU Knight CI approved protocols. This low risk investigator initiated study may be randomly audited by the DSMC audit team.

Inclusion of Women and Minorities(only if applicable)

No OHSU Knight Cancer Institute study will focus on any particular racial or ethnic subset. No subject will be excluded from the study based on racial or ethnic origin. Male, female and minority volunteers will be included in this study and approximately 50% men and 50% women will be studied. Or This breast cancer study includes only women. Or This prostate cancer study includes only men.

If the data is not available include this statement and don’t use the tables.

However, because this study utilizes only de-identified specimens that cannot be traced to an individual, it is not possible to track the gender and ethnicity.

Or use the % in table 1 to complete table 2 for your studies anticipated accrual, then delete table 1:

Table 1: Population Demographics - Oregon (%)

Ethnic Category / Sex/Gender
Females / Males / Total
Hispanic or Latino / 8.0
Not Hispanic or Latino / 92.0
Ethnic Category: Total of all subjects* / 100*
Racial Category
American Indian or Alaskan Native / 1.3
Asian / 3.0
Black or African American / 1.6
Native Hawaiian or other Pacific Islander / 0.2
White / 86.6
More than one race / 3.1
Unknown/Other / 4.2
Racial Category: Total of all subjects* / 100*
TOTALS / 50.4 / 49.6 / 100*

Source: Adapted from U.S. Census Bureau, 2000 *Totals may not equal 100 due to rounding.

Table 2: Projected Accrual for the Present Study(enter actual estimates, not percentages. If the calculation is less that 1,Do not inter “0” for any gender or minority category unless there is a protocol reason to exclude them. If the calculation is less that 1, enter 0-1.

Ethnic Category / Sex/Gender
Females / Males / Unknown / Total
Hispanic or Latino
Not Hispanic or Latino
Unknown
Ethnic Category: Total of all subjects* / *
Racial Category
American Indian or Alaskan Native
Asian
Black or African American
Native Hawaiian or other Pacific Islander
White
More than one race
Unknown
Racial Category: Total of all subjects* / *

*Totals must agree.

10.9.2 Inclusion of Children

In accordance with NIH guidelines on the inclusion of children as participants in research involving human subjects, children under the age of 18 years must be included in all human subjects research, conducted or supported by the NIH, unless there are clear and compelling reasons not to include them. Therefore, proposals for research involving human subjects must include a description of plans for the inclusion of children

Include the appropriate following statement:

This protocol includes children.

Or

This protocol does not include children for the following reason: (Acceptable reasons may be one or more of the following) 1. the number of children with this type of cancer is limited, or 2. samples from children are not available.

8.REFERENCES(required)

Provide the citations for all publications referenced in the text.

APPENDIX A(only if applicable)

Data Collection Forms

APPENDIX B(only if applicable)

Shipping Instructions

Insert protocol version date1