DCP CONSORTIA CHEMOPREVENTION PROTOCOL TEMPLATE

[INSTRUCTIONS]{.underline}

The protocol template is a tool to facilitate rapid protocol
development. It is not intended to supersede the role of the Protocol
Principal Investigator in the authoring and scientific development of
the protocol. It contains the language required in protocols submitted
to the NCI, Division of Cancer Prevention (DCP). Please modify all
sections as necessary to meet the scientific aims of the study and
development of the protocol.

1.  Each protocol submission consists of four parts:

    a.  DCP Consortia Protocol Submission Worksheet (PSW): This document
        contains prompts for required administrative information. The
        PSW is required for all protocol submissions including the
        original protocol, revisions and amendments. It is available at
        <http://prevention.cancer.gov/files/clinical-trials/consortia_psw.doc>

    b.  Main Body and Appendices of the protocol: This document provides
        standard language plus instructions and prompts for information
        required in each DCP protocol. The current protocol template is
        attached to these instructions, and is available at
        <http://prevention.cancer.gov/clinicaltrials/management/pio/instructions>.
        Please ensure the current version of the template always is used
        for protocol development.

    c.  Additional Study-Related Documents: These documents include the
        Recruitment and Retention Plan, the Pharmacokinetic and
        Biomarker Methods Development Report, the Case Report Forms
        (CRFs) and attachments, the Data Management Plan (DMP), the
        Multi-Institutional Monitoring Plan (MIMP), and the Data and
        Safety Monitoring Plan (DSMP).

> The Recruitment and Retention Plan, Pharmacokinetic and Biomarker
> Methods Development Report, CRFs and attachments, and
> protocol-specific addenda to the DMP, MIMP and DSMP are submitted with
> the initial protocol. These documents are [not]{.underline} considered
> an integral part of the protocol. Unless required by local practices,
> these documents do not need to be submitted to the local IRB and
> should not be referenced in the protocol.
>
> The PSW includes a checklist for all study-related documents
> (protocol, informed consent, and additional study-related documents)
> that must accompany each protocol submission. The DMP, MIMP, and DSMP
> have been standardized and approved for each consortium. Please
> reference these approved plans on the PSW, and submit supplemental
> information or addenda to these plans (e.g., a protocol-specific
> addendum to the DMP) [only as required]{.underline}.

d.  Protocol budget

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2.  An "administratively complete" protocol submission must include the
    following components:

    a.  First submission

        i.  DCP Consortia Protocol Submission Worksheet

        ii. Protocol including the informed consent document

            1.  A protocol document version number and date must be on
                the cover page.

            2.  All pages of the protocol must include a header that
                identifies the protocol by DCP protocol number, protocol
                document version date and version number. Pagination
                must be complete.

            3.  The table of contents sections and page numbers must
                match the protocol

        iii. All appendices (correct header and pagination)

        iv. All Additional Study-Related Documents (Recruitment and
            Retention Plan, Pharmacokinetic and Biomarker Methods
            Development Report, CRFs and attachments, supplemental
            information or addenda to the standardized DCP-approved
            documents (DMP, MIMP, and DSMP).

        v.  Protocol budget

    b.  All subsequent submissions (protocol revisions and amendments)
        must include:

        i.  Cover letter with a point-by-point response to DCP reviewer
            required and recommended changes with references to the
            changed document section.

        ii. An updated Protocol Submission Worksheet (PSW)

        iii. Amended protocol budget, if applicable,

> or a statement indicating that the proposed revision or amendment will
> not result in a change to the budget.

iv. "Tracked changes " or highlighted version of the protocol with
    informed consent and study-related documents, as appropriate,
    indicating changes from previous version

v.  Clean copy of all documents with highlights removed

vi. Any changes to the CRFs or other study-related documents resulting
    from a protocol revision or amendment must be included with the
    submission for review and approval.

vii Standard font indicates suggested language that should be retained
in the document.

vii. **Bold font** indicates language that must be retained in the
     document

viii Blank space or \_\_\_\_\_\_\_\_ indicates that you should fill in
the appropriate information.

> "Administratively Incomplete" submissions will be returned to the
> Consortium Lead PI for completion. The review process will begin
> following receipt of an administratively complete submission.

3.  All sections in the Protocol Template should be retained within the
    body of the document. If not appropriate for a given study, please
    insert "Not Applicable" after the section number and delete the
    corresponding text.

4.  *All Protocol Template instructions and prompts are in italics*.
    *Italicized information should be deleted prior to submitting the
    protocol to DCP.*

5.  DCP terminology for changes to protocol

    a.  Changes made prior to the initial DCP study approval are
        "Revisions"

    b.  Changes made after DCP approval are "Amendments"

6.  Indicate changes using the 'tracked changes' function, highlighting,
    or underlining new or modified text in protocol revisions or
    amendments to facilitate the review process.

7.  All document submissions must be sent electronically to Head, DCP
    Protocol Information Office (<NCI_DCP_PIO@mail.nih.gov>). Documents
    submitted elsewhere will not be accepted for review.

8.  DCP Consortia forms are available at
    <http://prevention.cancer.gov/clinicaltrials/management/pio/instructions>.
    Additional information is available on the DCP website at
    <http://prevention.cancer.gov/clinicaltrials/management/consortia>.

**Questions:**

**Contact the DCP Protocol Information Office at (301) 496-0090 or
e-mail <NCI_DCP_PIO@mail.nih.gov>**

.

COVER PAGE

**DCP Protocol #:** *This number will be assigned by DCP and may be the
same as or different from the local protocol number. The DCP protocol
number must appear on all protocol document versions and all
communication to DCP.*

**Local Protocol #:** *Insert your local protocol \# for this study. If
a local protocol number has not been assigned, indicate 'pending'.
DEFINITION: The local protocol number is assigned by the Lead
Organization according to local institutional conventions or Consortium
guidelines.*

[**PROTOCOL** **TITLE**]{.underline}

**Consortium Name:** *Insert name of Consortium*

**Name of Consortium Principal** *Name & Title of the Principal
Investigator of Consortium Lead Organization*

**Investigator:** *Address*

*Address*

*Telephone*

*Fax*

*E-mail address*

**Organization Name:** *Organization name*

**Protocol Principal Investigator:** *Protocol Principal Investigator*

*Investigator's Specialty*

*Address*

*Address*

*Telephone*

*Fax*

*E-mail address*

**Organization:** *Organization name*

**Investigator:** *Investigator's Name*

*Investigator's Specialty*

*Address*

*Address*

*Telephone*

*Fax*

*E-mail address*

**Organization:** *Organization name*

**Investigator:** *Investigator's Name*

*Investigator's Specialty*

*Address*

*Address*

*Telephone*

*Fax*

*E-mail address*

**Organization:** Organization *Name*

**Statistician:** *Statistician Name*

*Address*

*Address*

*Telephone*

*Fax*

*E-mail address*

***NOTE: If this is a multi-institution study:***

1.  ***The protocol title page(s) [must]{.underline} include the name
    and address of [each participating institution]{.underline} and any
    [affiliates participating in the study]{.underline}.***

2.  ***The protocol title page(s) must include the names of [all
    investigators]{.underline} at each institution; his/her telephone,
    Fax, and e-mail address.***

3.  ***Indicate the protocol lead investigator responsible for the study
    at each institution; his/her telephone, Fax, and e-mail address.***

**IND Sponsor:** *NCI/Division of Cancer Prevention (or other Sponsor)*

*6130 Executive Blvd., Room 2117*

> *Bethesda, MD 20892 (For FedEx, use Rockville, MD 20852)*

*(301) 496-8563*

**IND# \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**

**Agent(s)/Supplier**: *[Study Agent(s)/Supplier Name]{.underline}*

**NCI Contract \#** [N01-CN-*xxxxx *]{.underline}

**Protocol Version Date:** \_\_\_\_\_ *[(Date)]{.underline}* \_\_\_\_\_

**Protocol Revision or**

**Amendment \#** *[Revision or Amendment \#]{.underline}*

**SCHEMA**

*Please provide a schema for the study.*

*Protocol Title*

*Study Population*

*Baseline data collection*

*Randomization*

*Intervention*

*Endpoints*

**TABLE OF CONTENTS**

Page

**COVER PAGE**

**SCHEMA**

**1. OBJECTIVES**

1.  Primary Objectives

2.  Secondary Objectives

**2. BACKGROUND**

2.1 *[Study Disease]{.underline}*

2.2 *[Study Agent]{.underline}*

2.3 Rationale

3.  **SUMMARY OF STUDY PLAN**

**4. PARTICIPANT SELECTION**

1.  Inclusion Criteria

2.  Exclusion Criteria

3.  Inclusion of Women and Minorities

4.  Recruitment and Retention Plan

**5. AGENT ADMINISTRATION**

1.  Dose Regimen and Dose Groups

2.  \_*[(Study Agent]{.underline}**) ***Administration

3.  Run-In Procedures

4.  Contraindications

5.  Concomitant Medications

6.  Dose Modification

7.  Adherence/Compliance

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6.  **PHARMACEUTICAL INFORMATION**

    1.  Study Agent (IND #, IND Sponsor)

    2.  Reported Adverse Events and Potential Risks

    3.  Availability

    4.  Agent Distribution

    5.  Agent Accountability

    6.  Packaging and Labeling

    7.  Storage

    8.  Randomization

    9.  Blinding and Unblinding Methods

    10. Agent Destruction/Disposal

7.  **CLINICAL EVALUATIONS AND PROCEDURES**

> 7.1 Schedule of Events

2.  Baseline Testing/Prestudy Evaluation

3.  Evaluation During Study Intervention

4.  Evaluation at Completion of Intervention

5.  Post-intervention Follow-up Period

6.  Methods for Clinical Procedures

**8. CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION**

1.  Primary Endpoint

2.  Secondary Endpoints

3.  Off Agent Criteria

4.  Off Study Criteria

5.  Study Termination

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9.  **CORRELATIVE/SPECIAL STUDIES**

    0.  Comparable Methods

        Rationale for Methodology Selection

10. **SPECIMEN MANAGEMENT**

    0.  Laboratories

        Collection and Handling Procedures

        Shipping Instructions

        Tissue Banking

**11. REPORTING ADVERSE EVENTS**

1.  Adverse Events

2.  Serious Adverse Events

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12. **STUDY MONITORING**

    1.  Data Management

    2.  Case Report Forms

    3.  Source Documents

    4.  Data and Safety Monitoring Plan

    5.  Sponsor or FDA Monitoring

    6.  Record Retention

    7.  Cooperative Research and Development Agreement (CRADA)/

Clinical Trials Agreement (CTA**)**

13. **STATISTICAL CONSIDERATIONS**

    1.  Study Design/Endpoints

    2.  Sample Size/Accrual Rate

    3.  Randomization and Stratification

    4.  Primary Endpoint(s)

    5.  Secondary Endpoint(s)

    6.  Reporting and Exclusions

    7.  Evaluation of Toxicity

    8.  Evaluation of Response

    9.  Interim Analysis

    10. Ancillary Studies

14. **ETHICAL AND REGULATORY CONSIDERATIONS**

    1.  Form FDA 1572

    2.  Other Required Documents

    3.  Institutional Review Board Approval

    4.  Informed Consent

    5.  Submission of Regulatory
        Documents\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...

    6.  Other

**15. Financing, Expenses, and/or Insurance**

**REFERENCES**

**CHEMOPREVENTION INFORMED CONSENT TEMPLATE**

**APPENDICES**

**APPENDIX A**

Performance Status Criteria A-1

1.  **OBJECTIVES**

> *Study objectives are concise statements of the primary and secondary
> clinical and statistical questions that the study is designed to
> answer. Each objective should be stated as specifically and succinctly
> as possible. Both primary and secondary hypotheses must relate to the
> hypotheses presented in the rationale (section 2.3) and should be
> consistent with the objectives described in the statistical section
> (section 13.0). Clearly differentiate between primary and secondary
> objectives. Number the objectives in order of priority.*
>
> **1.1**. *Insert primary protocol objective.*

**1.2**. *Insert secondary protocol objectives, if pertinent.*

**2. BACKGROUND**

**2.1** ***[Study Disease]{.underline}***

*Please provide background information on the study disease. (May not be
applicable in Phase I trials).*

**2.2** ***[Study Agent]{.underline}***

> *Please provide background information on the study agent, including
> information to support safety issues and the rationale for the study
> dose and duration of exposure.*

**2.3** **Rationale**

> *Please provide the background rationale for evaluating this agent in
> this cohort/target organ. Present possible mechanisms and/or
> theoretical framework for conducting the study. Include relevant
> literature review and pertinent preclinical, pilot, and preliminary
> and/or unpublished data to support conduct of the trial. Clearly state
> the hypotheses for the primary and secondary objectives. Justify
> selection of target population, agent, endpoints and choice of
> techniques for endpoint assessment, measurement of drugs, metabolites
> and drug effects. Describe the contributions that the proposed study
> will make to the current knowledge base.*

3.  **SUMMARY OF STUDY PLAN**

*For the convenience of the reader, this section should provide a brief
synopsis of the following points:*

-   *Study design*

-   *Number of participants to be enrolled (total number and number per
    arm)*

> *Example: A maximum of 25 participants will be accrued into each of
> four intervention arms. Three additional participants are anticipated
> to accrue per arm to account for an anticipated drop out rate of 10%.
> Assuming a screening rate of approximately 25 participants per month
> and an accrual rate of approximately 8-10 participants per month, we
> expect the study to be complete within 18-24 months.*

-   *Brief description of the study population*

-   *Intervention plan, including doses, dose groups, and duration of
    exposure to the study agent.*

> *Example: Participants will be given two 30 gram tubes of study agent
> at the baseline visit and at months 3, 6, 9, and 12. Participants will
> take study agent for 54 +/- 2 weeks (minimum) to 102 +/- 2 weeks
> (maximum). Duration of administration will depend on when a
> participant is randomized in relationship to when the final
> participant is randomized. The study will be terminated when all
> participants have...*

-   *Description of run-in period, if applicable.*

-   *Time points for performing study assessments*

-   *Description of measurements taken to meet study objectives*

-   *Description of clinical procedures, lab tests or other measurements
    taken to monitor effects of study agent on human safety and to
    minimize risks*

-   *Duration of study*

4.  **PARTICIPANT SELECTION**

> **4.1** **Inclusion Criteria**
>
> 4.1.1 *Please insert specific health risk or disease requirements.*
> *State methods for assessing risk or disease requirements, e.g., risk
> assessment tools, clinical evaluation, pathology review criteria, etc.
> For populations with cancer or pre-cancer, include requirements for
> histological confirmation of diagnosis, time from diagnosis, and
> disease status at entry.*

2.  *Please state allowable type and amount of prior therapy, if
    applicable. Include separate definitions for duration as needed.
    Include site/total dose for prior radiation exposure as needed.*

3.  Age 18 years. *Please state reason for age restriction. If
    applicable, the following text can be used*.

> Because no dosing or adverse event data are currently available on the
> use of *[Study Agent]{.underline}* in participants \<18 years of age,
> children are excluded from this study but will be eligible for future
> pediatric trials, if applicable.
>
> 4.1.4 *ECOG performance status 1(Karnofsky 70%;* see Appendix A)

4.1.5 Participants must have normal organ and marrow function as defined
below:

> *Insert baseline lab parameters appropriate to agent and cohort, for
> example:*

-   *Leukocytes 3,000/μL*

-   *Absolute neutrophil count 1,500/μL*

-   *Platelets 100,000/μL*

-   *Total bilirubin within normal institutional limits*

-   *AST (SGOT)/ALT (SGPT) ≤1.5 X institutional ULN*

-   *Creatinine within normal institutional limits*

4.1.6 *Insert other appropriate inclusion criteria relevant to the
methodology of the study.*

4.1.7 *Please use or modify the following paragraph as appropriate:*

> The effects of *[Study Agent]{.underline}* on the developing human
> fetus at the recommended therapeutic dose are unknown. For this reason
> and because *[Agent Class]{.underline}* are known to be teratogenic,
> women of child-bearing potential and men must agree to use adequate
> contraception (hormonal or barrier method of birth control;
> abstinence) prior to study entry and for the duration of study
> participation. Should a woman become pregnant or suspect she is
> pregnant while participating in this study, she should inform her
> study physician immediately.

4.1.8 Ability to understand and the willingness to sign a written
informed consent document.

**4.2 Exclusion Criteria**

1.  *List contraindications to participation based on agent pharmacology
    and metabolism, toxicology, clinical and methodology
    considerations.*

2.  *Healthy volunteers may be required to demonstrate absence of
    chronic medical conditions or regular use of certain medications.*

3.  Participants may not be receiving any other investigational agents.

4.  History of allergic reactions attributed to compounds of similar
    chemical or biologic composition to *[Study Agent.]{.underline}*

5.  Uncontrolled intercurrent illness including, but not limited to,
    ongoing or active infection, symptomatic congestive heart failure,
    unstable angina pectoris, cardiac arrhythmia, or psychiatric
    illness/social situations that would limit compliance with study
    requirements.

6.  *The investigator(s) must state a medical or scientific reason if
    pregnant or nursing participants or participants who are cancer
    survivors or those who are HIV-positive will be excluded from the
    study. Detailed information regarding these special populations is
    available in the DCP Clinical Trials Resource. Suggested text is
    provided below:*

> Pregnant women are excluded from this study because *[Study
> Agent]{.underline} is [a/an Agent Class ]{.underline}* agent with the
> potential for teratogenic or abortifacient effects. Because there is
> an unknown but potential risk for adverse events in nursing infants
> secondary to treatment of the mother with *[Study Agent,]{.underline}*
> Breastfeeding should be discontinued if the mother is treated with
> *[Study Agent.]{.underline}*

**4.3 Inclusion of Women and Minorities**

*Both men and women (as applicable)* and members of all races and ethnic
groups are eligible for this trial.

> *Women and members of minority groups and their subpopulations must be
> included in the study population of research involving human subjects,
> unless a clear and compelling rationale and justification are provided
> indicating that inclusion is inappropriate with respect to the health
> of the participants or the purpose of the research. NIH requires
> accrual estimates by gender/race/ethnicity. This information should be
> recorded on the DCP Protocol Submission Worksheet (PSW). Additional
> information regarding the NIH policy is available in the Early Phase
> Prevention Trials Consortia section of the DCP website Resource.*

**4.4 Recruitment and Retention Plan**

> *Please provide a short synopsis of strategies to be used for
> recruitment and retention for the target population. However, the
> detailed specifics of the plan (including gender and minority
> recruitment strategies, as per NIH guidelines) must be provided in the
> Recruitment and Retention Plan that is part of the Additional
> Study-Related Documents submitted with the protocol. Since the
> detailed Recruitment and Retention Plan is not part of the protocol,
> please do not reference it here.*
>
> *Recruitment and retention efforts should be evaluated routinely by
> the study staff and modified as necessary to promote rapid accrual and
> to assure 100% retention of participants. Following initial review and
> approval by the DCP Protocol and Safety Review Committee (PSRC),
> revisions to the plan should be electronically submitted to the DCP
> Protocol Information Office.*
>
> *A sample generic Recruitment and Retention Plan is provided in the
> Additional Study-Related Document guidelines. The plan should include
> three phases: Pre-Initiation phase, Active Recruitment phase, and
> Retention phase (which include adherence strategies). The sample
> generic plan may be used as a guideline or checklist and is not
> intended to be followed in entirety nor to preclude any additional
> strategies. Recruitment and Retention Plans should be tailored to the
> characteristics of the individual protocol, sample size, target
> population, clinical sites and resources.*

**5. AGENT ADMINISTRATION**

Intervention will be administered on an
*[inpatient/outpatient]{.underline}* basis. Reported adverse events and
potential risks are described in Section 6.2.

**5.1 Dose Regimen and Dose Groups**

> *Please describe the regimen and dose groups. State any special
> precautions or warnings relevant for study agent administration. Each
> dose group should specify:*

-   *Agent(s)*

-   *Daily dose(s) and regimen(s) for each agent (e.g., two capsules
    bid)*

-   *Duration (days/weeks/months) for each agent.*

    2.  **[Study Agent]{.underline} Administration**

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-   *Indicate who will administer the agent,*

-   *How much agent (e.g., number of pills) should be administered at
    how many times/day (be specific for example: 20 mg capsules, 100
    capsule/bottle, 2 bottles distributed at the baseline visit and at
    months 3, 6, 9, etc.),*

-   *Time of day dose is to be taken,*

-   *Special instructions for taking the agent (e.g., with morning
    meal).*

    3.  **Run-in Procedures**

> *If the study includes a placebo run-in phase prior to randomization
> to assess compliance, please describe the procedure including method
> of administering placebo, dose, duration, and methods for assessing
> compliance. Compliance should be clearly defined.*

4.  **Contraindications**

> *Indicate any restrictions that participants should follow when using
> the agent (e.g., limit sun exposure, dietary restrictions, etc.).*

5.  **Concomitant Medications**

######### Indicate any limitations on medications, herbs, and vitamin and mineral supplements (other than study agents) while participating in the study. Include time period for the limitation,, if applicable.

> All medications (prescription and over-the-counter), vitamin and
> mineral supplements, and/or herbs taken by the participant will be
> documented on the concomitant medication CRF and will include: 1)
> start and stop date, dose and route of administration, and indication.
> Medications taken for a procedure (e.g., biopsy) should also be
> included.

**5.6 Dose Modification**

> *Explicitly identify when dose modifications are appropriate.
> Modifications and the factors predicating dose modification should be
> explicit and clear. If dose modifications are anticipated, please
> provide a dose de-escalation schema with modifications expressed as a
> specific dose or amount rather than as a percentage of the starting or
> previous dose. Also indicate if the agent supply may be used for dose
> modifications or will an additional supply (smaller doses) be needed
> to achieve dose modification. If applicable, describe procedures for
> increasing dose following a toxicity-required dose reduction.*
>
> **5.7 Adherence/Compliance**

1.  *Provide* *a definition of compliance that will be used to describe
    when participants are considered evaluable for statistical analysis*

> *.*
>
> 5.7.2 *Describe* *the method(s) used to monitor each* *participant's
> agent compliance. Methods may include diaries, pill counts,
> drug/metabolite plasma levels, and/or drug effect biomarkers.*

**6. PHARMACEUTICAL INFORMATION**

> **6.1 [Study Agent (IND #, IND Sponsor)]{.underline}**
>
> *Confidential pharmaceutical information for investigational study
> agents supplied by NCI, DCP will be provided as an attachment to the
> LOI approval letter and should be inserted here.*

*Non-DCP supplied agents: insert appropriate agent information here.
Specify:*

-   *Formulation to be used in this study*

-   *Justification for this formulation if other formulations are
    available,*

-   *Physical description of agent*

-   *List of excipients*

##### 

##### 6.2 Reported Adverse Events and Potential Risks

> *The list of "Reported Adverse Events and Potential Risks" included in
> the LOI approval letter should be inserted here.*
>
> *Non-DCP supplied agents: describe the toxicity profile and related
> data for the agent at the selected doses and schedule.*
>
> **6.3 Availability**
>
> *[Study Agent]{.underline}* is an investigational agent supplied to
> investigators by the Division of Cancer Prevention (DCP), NCI.
>
> *Example: Agent A and Agent B are investigational agents for
> chemoprevention studies provided by NCI/DCP. Agent C will be supplied
> to NCI/DCP by XXX (20 mg capsules, 30 capsules/bottle). Agent D and
> matching placebo D will be supplied to NCI/DCP by XXX (50 mg capsules,
> 30 capsules/bottle).*

*Non-DCP supplied agents: delete the above statement and specify source
and availability of supply.*

> *Example: Agent XXX and matching placebo will be manufactured and
> supplied by XXX. Agent XXX and matching placebo will be packaged in
> bottles containing 100 capsules.*
>
> *If the study agent is provided by NCI under a Cooperative Research
> and Development Agreement (CRADA) or Clinical Trials Agreement (CTA)
> with the manufacturer, the appropriate text below must be included in
> the protocol **and the incorrect text deleted**. Information on the
> study agent's CRADA/CTA status will be provided in LOI approval
> letter.*
>
> [*Study Agent*]{.underline} is provided to the NCI under a Cooperative
> Research and Development Agreement (CRADA) between *[Agent
> Manufacturer]{.underline}* and the DCP, NCI (see Section 12.7).
>
> [*Study Agent*]{.underline} is provided to the NCI under a Clinical
> Trials Agreement (CTA) between *[Agent Manufacturer]{.underline}* and
> the DCP, NCI (see Section 12.7).
>
> **6.4  Agent Distribution**
>
> Agents will only be released by NCI, DCP after documentation of IRB
> approval of the DCP-approved protocol and consent is provided to DCP
> and the collection of all Essential Documents is complete (see DCP
> website for description of Essential Documents).
>
> NCI, DCP-supplied agents may be requested by the Investigator (or
> their authorized designees) at each Organization.  DCP guidelines
> require that the agent be shipped directly to the institution or site
> where the agent will be prepared and administered.  DCP does not
> permit the transfer of agents between institutions (unless prior
> approval from DCP is obtained).  [DCP does not automatically ship
> agents; the site must make a request.]{.underline} Agents are
> requested by completing the DCP Clinical Drug Request form (NIH-986)
> (to include complete shipping contact information) and faxing or
> mailing the form to the DCP agent repository contractor:

Jennifer E. Benkstein, Ph.D.

Principal Investigator

ThermoFisher BioServices

DCP Repository

20301 Century Blvd., Bldg 6, Suite 800

Germantown, MD 20874

Phone (direct) 240-686-4722; cell 240-388-4721

Fax: 301-515-4297

<Jennifer.benkstein@thermofisher.com>

> *For non-DCP supplied agents indicate the manufacturer, supplier and
> mechanism for distribution.*

*DCP procedures for agent distribution and the required forms are
available on the DCP website.*

> **6.5 Agent Accountability**
>
> The Investigator, or a responsible party designated by the
> Investigator, must maintain a careful record of the inventory and
> disposition of all agents received from DCP using the NCI Drug
> Accountability Record Form (DARF). The Investigator is required to
> maintain adequate records of receipt, dispensing and final disposition
> of study agent. This responsibility has been delegated to \_\_\_\_
> \[*insert responsible party\] \_\_\_.* Include on receipt record from
> whom the agent was received and to whom study agent was shipped, date,
> quantity and batch or lot number. On dispensing record, note
> quantities and dates study agent was dispensed to and returned by each
> participant.

*DCP requirements for agent accountability and the required forms are
available on the DCP website.*

6.  **Packaging and Labels**

> \_\_\_\[Agent\]\_\_ will be packaged by \_\_\[manufacturer or NCI,
> DCP\]\_\_\_.
>
> *DCP will package, label and distribute agent for all DCP-supplied
> agents. Occasionally, a pharmaceutical collaborator or the site
> performs one or more of these activities. DCP will send a draft label
> to the Principal Investigator and the DCP regulatory support
> contractor for review and approval. Final labels are printed and
> attached to the bottle prior to shipping to the site. DCP will provide
> information regarding packaging (container, amount of agent per
> container) and labeling in the LOI approval letter. The information
> provided by DCP should be inserted into this section of the protocol.*
>
> *Example: Each bottle will be labeled with a one-part label
> identifying study specific information, such as Study title, DCP
> protocol number, dosing instructions, recommended storage conditions,
> the name and address of the distributor, randomization number, and a
> caution statement indicating that the agent is limited by United
> States law to investigational use only and the agent should be kept
> out of reach of children.*
>
> *Protocols using non-DCP supplied agents: describe in detail how the
> agent will be packaged and distributed, including container, amount of
> agent per container, container label information, and if blinded, how
> the label will be constructed to maintain the blind. Label information
> should include dose, number of doses per day, time of day for dosing,
> with or without food, and any other specific instructions.*

7.  **Storage**

> *Provide instructions regarding proper storage of the agent at the
> study site(s). Storage temperatures should be expressed as a range,
> not a specific number. For example, room temperature should be
> specified (e.g., between 59°F and 86°F).*

**6.8 Registration/Randomization**

> *Give specific details on how a participant will be registered in a
> trial. For randomized trials, describe the procedure for randomizing a
> participant to a dose group. (May refer to Section 13.3).*

#######  {#section-1 .unnumbered}

####### 6.9 Blinding and Unblinding Methods {#blinding-and-unblinding-methods .unnumbered}

> *For blinded studies, describe blinding and unblinding methods.
> Address the following points:*

-   *Procedure for retaining the blind (including specific procedures
    for protecting the blind should data collected in the study offer
    evidence of a participant's assignment to a particular study arm)*

-   *Individual authorized to break the blind*

-   *Circumstances for breaking the blind*

-   *Procedure for breaking the blind*

*The NCI Medical Monitor and/or Scientific Monitor must be notified that
the blind has been broken.*

> *Provide DCP Medical Monitor Name and title (see LOI Decision Letter)*

NCI/Division of Cancer Prevention

*Insert the full contact information including address, telephone
number, FAX number, and email of the DCP Medical Monitor*

**6.10 Agent Destruction/Disposal**

> DCP-supplied agents: at the completion of investigation, all unused
> study agent will be returned to NCI, DCP Repository according to the
> DCP "Guidelines for AGENT RETURNS" and using the DCP form "Return Drug
> List".

*The Guidelines and form are available on the DCP website.*

> *Non-DCP agents, provide the following procedure for handling the
> unused drug: method of disposal, documentation of disposal, and any
> other relevant standard operating procedures.*

**7. CLINICAL EVALUATIONS AND PROCEDURES**

**7.1 Schedule of Events**

> *A table that lists baseline testing/pre-study evaluation, agent
> administration, study assessments, procedures and case report forms
> should be included. A sample schedule of events is provided on the
> following page. The protocol should state the expected duration of
> participation in the study and the sequence and duration of all trial
> periods, including follow-up, if any.*
>
> **7.2 Baseline Testing/Pre-study Evaluation**
>
> *Describe all procedures (including registration and randomization)
> that must be completed for a participant before the study intervention
> may begin. Note any time restrictions for testing (e.g., pre-study
> labs must be done within 14 days of registration).*
>
> *Specify the amount of study agent that will be distributed to the
> participant at each visit. Also describe how the participant will
> return study agent for example: Day 0, participants will be randomized
> to receive either study agent or placebo and will be given a supply of
> study agent (3 bottles for a total of 90 capsules); day 60,
> participants will return any unused study agent and will be given a
> supply of study agent (3 bottles for a total of 90 capsules).*

*Refer to Section 5.3, Run-In Procedures, if applicable.*

> **7.3 Evaluations During Study Intervention**

*Indicate the procedures to be performed during the study intervention
phase.*

4.  **Evaluations at Completion of Study Intervention**

> *Specify the evaluations that must be performed at the discontinuation
> of study agent. Ensure that these evaluations are consistent with the
> endpoints described in the objectives and statistical analysis
> sections of the protocol.*

5.  **Post-intervention Follow-up Period**

> *If a defined post-intervention follow-up period is required, specify
> observations or tests to be performed. Define the length and purpose
> of the follow-up period.*

6.  **Methods for Clinical Procedures**

> *If applicable, document any special processes, instructions or
> methodology for clinical procedures required by the protocol, such as
> invasive procedures and imaging. Include special instructions for
> procedure prep (e.g., NPO after midnight) and scheduling instructions
> for tests that may be available only at certain locations or times.*

**SCHEDULE OF EVENTS**

  -------------- -------------- ---------- --------------- -------- -------- ------------- --------
  Evaluation/    Registration   Baseline   Randomization   Months   Months 4 Month 6 or    Follow
  Procedure                                                1-3      and 5    Early         Up Visit
                                                                             Termination   

  Informed       X                                                                         
  Consent                                                                                  

  Assess         X              X                                                          
  Eligibility                                                                              

  Medical                       X                                                          
  History                                                                                  

  Physical Exam                 X                                                          

  Vital Signs/                  X                          X                 X             
  Height and                                                                               
  Weight                                                                                   

  Laboratory                    X                          X                 X             
  Tests                                                                                    

  X-Rays                        X                                            X             

  EKG                           X                                            X             

  Biopsies                      X                                            X             

  Biomarkers                    X                                            X             

  Study                         X                          X                 X             
  Evaluations/                                                                             
  Assessments                                                                              

  Concomitant                   X                          X        X        X             X
  Medications                                                                              

  Dispense Study                           X               X                               
  Agent                                                                                    

  Collect Study                                                              X             
  Agent                                                                                    

  Review Agent                             X               X                 X             
  Diary/Record                                                                             

  Adverse Events                                           X        X        X             X

  Telephone                                                         X                      X
  Contact                                                                                  
  -------------- -------------- ---------- --------------- -------- -------- ------------- --------

**8. CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION**

*Delineation of study endpoints, methods for measuring or evaluating,
and timing of endpoint ascertainment should be described here.*

1.  **Primary Endpoint**

> *Depending on the study hypotheses and design, the primary endpoint
> may be an incidence of invasive or preinvasive disease (e.g., polyp
> incidence), clinical response (e.g., change in number and severity of
> leukoplakia by physical exam), histologic or cytologic response (e.g.,
> change in severity of dysplasia in biopsy materials), and/or
> modulation of surrogate endpoint biomarkers (SEBs). Define endpoints
> clearly and briefly describe methods and intervals for assessment. A
> detailed description of methods should be included in the
> Pharmacokinetic and Biomarker Method Development Report document (part
> of the Additional Study-Related Documents that are submitted with the
> protocol) as appropriate. Do not reference the Pharmacokinetic and
> Biomarker Method Development Report here since it is not an actual
> part of the protocol.*

2.  **Secondary Endpoints**

> *As appropriate, secondary endpoints (serum/plasma/tissue
> agent/metabolite levels, other agent effect biomarkers) should be
> defined clearly. Methods for assessment should be referenced in this
> section with detailed descriptions of laboratory and computer modeling
> procedures provided in the required "Pharmacokinetic and Biomarker
> Method Development Report" document (part of the additional
> Study-Related Documents).*

3.  **Off Agent Criteria**

> Participants may stop taking study agent for the following reasons:
> completed the protocol-prescribed intervention, adverse event or
> serious adverse event, inadequate agent supply, noncompliance,
> concomitant medications, medical contraindication, or [­­­ *specify other
> reasons, if applicable* .]{.underline} Participants will continue to
> be followed, if possible, for safety reasons and in order to collect
> endpoint data according to the schedule of events. *The protocol
> should state whether and how subjects are to be replaced, if
> applicable.*

4.  **Off Study Criteria**

> Participants may go 'off-study' for the following reasons: the
> protocol intervention and any protocol-required follow-up period is
> completed, adverse event/serious adverse event, lost to follow-up,
> non-compliance, concomitant medication, medical contraindication,
> withdraw consent, death, determination of ineligibility, pregnancy, or
> *specify other reasons, if applicable*.

5.  **Study Termination**

> NCI, DCP as the study sponsor has the right to discontinue the study
> at any time.

####### CORRELATIVE/SPECIAL STUDIES

6.  **Rationale for Methodology Selection**

> *Provide the rationale for selecting the assay methodology,
> particularly in cases where various assays are available that may
> assess different qualities of the marker (example: mutation analysis
> vs. IHC for p53; gene expression vs. protein expression). Methodology
> should be included, as appropriate, in the Pharmacokinetic and
> Biomarker Methods Development Report.*

7.  **Comparable Methods**

> *Discuss the comparability of the methods proposed to those previously
> used and the likelihood that the resulting data will be able to be
> compared to existing data.*

**10. SPECIMEN MANAGEMENT**

> **10.1 Laboratories**
>
> *Identify the laboratory(ies) that will perform each analysis for each
> specimen. Where appropriate, list individuals who will perform
> analysis and/or procedures for conducting consensus reviews of
> specimens.*

**10.2 Collection and Handling Procedures**

#########  

#########  For each type of specimen obtained, please describe the following

####### *Amount to be collected*

-   *When specimen should be obtained (e.g., fasting, prior to a.m.
    dose)*

-   *Processing of specimen (e.g., details of tissue fixation,
    embedding, processing and sectioning)*

-   *Labeling of specimen*

-   *Tracking of specimens (e.g., logs or tracking sheets for
    participants)*

-   *Temperature storage requirements*

-   *Storage duration*

    *Note: If this section is too lengthy, please place this information
    in an appendix to the protocol.*

    3.  **Shipping instructions**

> *Include this section only if specimens will be shipped to an off-site
> laboratory for analysis. For each specimen, describe the following::
> packaging, carrier requirements, when specimens may be shipped, and
> name, address, and telephone number of the person to whom the
> specimens are being sent. Indicate compliance with the International
> Air Transport Association (IATA) Dangerous Goods Regulations.*

4.  **Tissue Banking**

> *Indicate methods and procedures for tissue banking here.*
>
> Biologic specimens collected during the conduct of each clinical trial
> that are not used during the course of the study will be considered
> deliverables under the contract and thus the property of the NCI. At
> study completion, NCI reserves the option to either retain or
> relinquish ownership of the unused biologic specimens. If NCI retains
> ownership of specimens, the Contractor shall collect, verify and
> transfer the requested biologic specimens from the site to a
> NCI-specified repository or laboratory at NCI's expense.

**11. REPORTING ADVERSE EVENTS**

> DEFINITION: An adverse event (AE) is any untoward medical occurrence
> in a study participant. An AE does not necessarily have a causal
> relationship with the treatment or study participant. An AE can
> therefore be any unfavorable and unintended sign (including an
> abnormal laboratory finding), symptom, or disease temporally
> associated with participation in a study, whether or not related to
> that participation. This includes all deaths that occur while a
> participant is on a study.
>
> A list of adverse events that have occurred or might occur (Reported
> Adverse Events and Potential Risks) can be found in Section 6.2,
> Pharmaceutical Information as well as the Investigator Brochure or
> package insert.
>
> **11.1 Adverse Events**

11.1.1 Reportable Adverse Events

> All adverse events that occur after the informed consent is signed
> (including run-in) must be recorded on the adverse event CRF (paper
> and/or electronic) whether or not related to study agent.

2.  AE Data Elements:

-   AE reported date

-   AE Verbatim Term

-   CTCAE Term (v 3.0)

-   Event onset date and event ended date

-   Severity grade

-   Attribution to study agent (relatedness)

-   Whether or not the event was reported as a Serious Adverse Event
    (SAE)

-   Whether or not the subject dropped due to the event

-   Action taken with the study agent

-   Outcome of the event

-   Comments

> 11.1.3 Severity of AEs

1.  Identify the adverse event using the NCI Common Terminology Criteria
    for Adverse Events (CTCAE) version 3.0. The CTCAE provides
    descriptive terminology and a grading scale for each adverse event
    listed. A copy of the CTCAE can be found at
    [http://ctep.cancer.gov](http://ctep.cancer.gov/).

> AEs will be assessed according to the CTCAE grade associated with the
> AE term. AEs that do not have a corresponding CTCAE term will be
> assessed according to their impact on the participant's ability to
> perform daily activities as follows:

+-------------+-------------+------------------------------------------+
| Grade       | Severity    | Description                              |
+-------------+-------------+------------------------------------------+
| 1           | Mild        | -   Barely noticeable, does not          |
|             |             |     influence functioning                |
|             |             |                                          |
|             |             | ```{=html}                               |
|             |             | <!-- -->                                 |
|             |             | ```                                      |
|             |             | -   Causing no limitations of usual      |
|             |             |     activities                           |
+-------------+-------------+------------------------------------------+
| 2           | Moderate    | -   Makes participant uncomfortable,     |
|             |             |     influences functioning               |
|             |             |                                          |
|             |             | ```{=html}                               |
|             |             | <!-- -->                                 |
|             |             | ```                                      |
|             |             | -   Causing some limitations of usual    |
|             |             |     activities                           |
+-------------+-------------+------------------------------------------+
| 3           | Severe      | -   Severe discomfort, treatment needed  |
|             |             |                                          |
|             |             | -   Severe and undesirable, causing      |
|             |             |     inability to carry out usual         |
|             |             |     activities                           |
+-------------+-------------+------------------------------------------+
| 4           | Life        | -   Immediate risk of death              |
|             | threatening |                                          |
|             |             | -   Life threatening or disabling        |
+-------------+-------------+------------------------------------------+
| 5           | Fatal       | -   Causes death of the participant      |
+-------------+-------------+------------------------------------------+

> 11.1.4 Assessment of relationship of AE to treatment
>
> The possibility that the adverse event is related to study drug will
> be classified as one of the following: not related, unlikely,
> possible, probable, definite.
>
> 11.1.5 Follow-up of AEs
>
> All AEs, including lab abnormalities that in the opinion of the
> investigator are clinically significant, will be followed according to
> good medical practices and documented as such.
>
> **11.2 Serious Adverse Events**

11.2.1 DEFINITION: ICH Guideline E2A and Fed. Reg. 62, Oct. 7, 1997
define serious adverse events as those events, occurring at any dose,
which meet any of the following criteria:

-   Results in death

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-   Is life threatening (*Note: the term life-threatening refers to an
    event in which the patient was at risk of death at the time of the
    event; it does not refer to an event which hypothetically might have
    caused death if it were more severe).*

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-   Requires inpatient hospitalization or prolongation of existing
    hospitalization

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-   Results in persistent or significant disability/incapacity

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-   Is a congenital abnormality/birth defect

-   Events that may not meet these criteria, but which the investigator
    finds very unusual and/or potentially serious, will also be reported
    in the same manner.

11.2.2 Reporting Serious Adverse Events to DCP

1.  The Lead Organization and all Participating Organizations will
    report SAEs on the DCP SAE form found at
    <http://prevention.cancer.gov/files/clinical-trials/SAE_formAugust_9_2006.doc>.

11.2.2.2 Contact the DCP Medical Monitor by phone within 24 hours of
knowledge of the event.

*Provide DCP Medical Monitor Name and title (see LOI Decision Letter)*

NCI/Division of Cancer Prevention

*Insert the full contact information including address, telephone
number, FAX number, and email of the DCP Medical Monitor*

Include the following information when calling the Medical Monitor:

-   Date and time of the SAE

-   Date and time of the SAE report

-   Name of reporter

-   Call back phone number

-   Affiliation/Institution conducting the study

-   DCP protocol number

-   Title of protocol

-   Description of the SAE, including attribution to drug and
    expectedness

3.  The Lead Organization and all Participating Organizations will FAX
    written SAE reports to the DCP Medical Monitor within 48 hours of
    learning of the event using the paper SAE form. The written SAE
    reports will also be FAX'ed to DCP's Regulatory Contractor, CCS
    Associates, at (650)691-4410 (phone: (650)691-4400).

4.  The DCP Medical Monitor and regulatory staff will determine which
    SAEs require FDA submission.

5.  The Lead Organization and all Participating Organizations will
    comply with applicable regulatory requirements related to reporting
    SAEs to the IRB/IEC.

11.2.2.6 Follow-up of SAE

Site staff should send follow-up reports as requested when additional
information is available. Additional information should be entered on
the DCP SAE form in the appropriate format. Follow-up information should
be sent to DCP as soon as available. *The protocol should state the
length of time for follow-up of an SAE. Usually SAEs are followed until
resolved, especially for those related to the study agent.*

**12. STUDY MONITORING**

> **12.1 Data Management**
>
> This study will report clinical data using the DCP Oracle^®^ Clinical
> Remote Data Capture (OC-RDC) web-based application managed by DCP's
> monitoring contractor. The OC-RDC will be the database of record for
> the protocol and subject to NCI and FDA audit. All OC-RDC users will
> be trained to use the RDC system and will comply with the instructions
> in the protocol-specific "RDC User Manual" provided to the Consortium
> Lead PI by the DCP Monitoring Contractor as well as applicable
> regulatory requirements such as 21 CFR; Part 11.
>
> *An approved Master Data Management Plan that is applicable to all
> studies within the Consortium will be on file at DCP. If there are any
> changes required to the Master DMP that are specific to this protocol
> only, then DMP Attachment #1 should be submitted with the protocol as
> part of the set of "Additional Study-Related Documents". Any changes
> or updates to the Master Data Management Plan following DCP approval
> should be submitted separately to the DCP Protocol Information Office
> for approval.*

**12.2 Case Report Forms**

> Participant data will be collected using protocol-specific case report
> forms (CRF) developed from the standard set of DCP Chemoprevention CRF
> Templates and utilizing NCI-approved Common Data Elements (CDEs). The
> approved CRFs will be used to create the electronic CRF (e-CRF)
> screens in the OC-RDC application. Site staff will enter data into the
> e-CRF for transmission to DCP according to pre-established DCP
> standards and procedures. Amended CRFs will be submitted to the DCP
> Protocol Information Office for review and approval. Approved changes
> will be programmed into the OC-RDC database by the DCP Monitoring
> Contractor.
>
> *The site will use DCP Chemoprevention CRF Templates from the DCP
> website to develop study-specific CRFs. The DCP templates contain NCI
> Common Data Elements (CDEs); use of these standardized terms
> facilitates data collection and analysis across studies. The standard
> template set may require modification to capture the unique data
> elements (i.e., biomarkers) of each protocol. NCI CDEs, where
> available, shall be used for all CRF modifications.*
>
> *The CRFs and attachments will be submitted with the protocol for DCP
> PSRC review as part of the set of "Additional Study-Related
> Documents". The DCP Monitoring Contractor will work with the sites to
> finalize the CRFs. DCP must approve the final CRFs prior to study
> initiation. CRFs may require changes throughout the conduct of the
> clinical trial. The need for change may result from protocol
> amendments or other reasons. Amended CRFs and attachments should be
> submitted to the DCP Protocol Information Office for review and
> approval. Studies may be initiated using paper CRFs.*

**12.3 Source Documents**

> *The protocol should state what constitutes a source document. Data
> recorded directly on the CRFs (i.e., no prior written or electronic
> record of data), which will be considered as source data should be
> identified.*

**12.4 Data and Safety Monitoring Plan**

NIH and NCI policy requires a Data and Safety Monitoring Plan (DSMP) to
document the institution's procedures to ensure safety of participants,
validity of data, and the appropriate termination of studies for which
significant benefits or risks have been uncovered or when it appears
that the trials cannot be concluded successfully. Risks associated with
participation in research must be minimized to the extent practical and
the method and degree of monitoring should be commensurate with risk.
The guidelines, essential elements and sample plans are available at:
<http://cancer.gov/clinicaltrials/conducting/dsm-guidelines>. Please
note that the requirements differ depending on whether a trial is
conducted under an IND.

An approved Master DSMP applicable to all studies within a Consortium
will be on file at DCP. If there are any changes required to the Master
DSMP that are specific to this protocol only, then DSMP Attachment #1
should be submitted with the protocol as part of the set of "Additional
Study-Related Documents".

Please provide a brief summary of the Master DSMP in this section.

**12.5 Sponsor or FDA Monitoring**

The NCI, DCP (or their designee), pharmaceutical collaborator (or their
designee), or FDA may monitor/audit various aspects of the study. These
monitors will be given access to facilities, databases, supplies and
records to review and verify data pertinent to the study.

Please refer to the monitoring section (Step 3) of the Early Phase
Prevention Trials area of the DCP website for information regarding DCP
site visit procedures and requirements.

**12.6 Record retention**

> Clinical records for all participants, including CRFs, all source
> documentation (containing evidence to study eligibility, history and
> physical findings, laboratory data, results of consultations, etc.),
> as well as IRB records and other regulatory documentation will be
> retained by the Investigator in a secure storage facility in
> compliance with HIPAA, OHRP, FDA regulations and guidances, and
> NCI/DCP requirements unless the standard at the site is more
> stringent. The records for all studies performed under an IND will be
> maintained, at a minimum, for two (2) years after the approval of a
> New Drug Application (NDA). For NCI/DCP, records will be retained for
> at least three (3) years after the completion of the research. NCI
> will be notified prior to the planned destruction of any materials.
> The records should be accessible for inspection and copying by
> authorized persons of the Food and Drug Administration. If the study
> is done outside of the United States, applicable regulatory
> requirements for the specific country participating in the study also
> apply.

**12.7 Cooperative Research and Development Agreement (CRADA)/Clinical
Trials Agreement (CTA)**

> *If the study agent is provided by DCP under a Cooperative Research
> and Development Agreement (CRADA) or Clinical Trials Agreement (CTA)
> with the manufacturer, this section must be included in the protocol,
> but the inappropriate text \[Clinical Trials Agreement (CTA)*
> [or]{.underline} *Cooperative Research and Development Agreement
> (CRADA)\]* *should be deleted. Information on the study agent's
> CRADA/CTA status will be provided in the approved LOI response. If
> neither a CRADA nor CTA applies to the study agent, this section
> should be marked "N/A" and the text below deleted.*
>
> The agent(s), supplied by DCP, NCI, used in this protocol is/are
> provided to the NCI under a Collaborative Agreement (CRADA, CTA)
> between the Pharmaceutical Company (ies) \[hereinafter referred to as
> ACollaborator(s)@\] and the NCI Division of Cancer Prevention.
> Therefore, the following obligations/guidelines, in addition to the
> provisions in the "Intellectual Property Option to Collaborator@
> contained within the terms of award, apply to the use of Agent(s) in
> this study:
>
> 12.8.1 Agent(s) may not be used for any purpose outside the scope of
> this protocol, nor can Agent(s) be transferred or licensed to any
> party not participating in the clinical study. Collaborator(s) data
> for Agent(s) are confidential and proprietary to Collaborator(s) and
> shall be maintained as such by the investigators. The protocol
> documents for studies utilizing investigational agents contain
> confidential information and should not be shared or distributed
> without the permission of the NCI. If a patient participating on the
> study or participant's family member requests a copy of this protocol,
> the individual should sign a confidentiality agreement. A suitable
> model agreement can be downloaded from the DCP website.
>
> 12.8.2 For a clinical protocol where there is an investigational Agent
> used in combination with (an) other investigational Agent(s), each the
> subject of different collaborative agreements, the access to and use
> of data by each Collaborator shall be as follows (data pertaining to
> such combination use shall hereinafter be referred to as \"Multi-Party
> Data".):

12.8.3 NCI must provide all Collaborators with prior written notice
regarding the existence and nature of any agreements governing their
collaboration with NIH, the design of the proposed combination protocol,
and the existence of any obligations that would tend to restrict NCI\'s
participation in the proposed combination protocol.

12.8.4 Each Collaborator shall agree to permit use of the Multi-Party
Data from the clinical trial by any other Collaborator solely to the
extent necessary to allow said other Collaborator to develop, obtain
regulatory approval, or commercialize its own investigational agent.

> 12.8.5 Any Collaborator having the right to use the Multi-Party Data
> from these trials must agree in writing prior to the commencement of
> the trials that it will use the Multi-Party Data solely for
> development, regulatory approval, and commercialization of its own
> investigational agent12.8.6 Clinical Trial Data and Results and Raw
> Data developed under a collaborative agreement will be made available
> exclusively to Collaborator(s), the NCI, and the FDA, as appropriate.
> All data made available will comply with HIPAA regulations.

12.8.6 When a Collaborator wishes to initiate a data request, the
request should first be sent to the NCI, who will then notify the
appropriate investigators of Collaborator\'s wish to contact them.

> 12.8.7 Any manuscripts reporting the results of this clinical trial
> must be provided to DCP for immediate delivery to Collaborator(s) for
> advisory review and comment prior to submission for publication.
> Collaborator(s) will have 30 days (or as specified in the CTA) from
> the date of receipt for review. Collaborator shall have the right to
> request that publication be delayed for up to an additional 30 days in
> order to ensure that Collaborator's confidential and proprietary data,
> in addition to Collaborator(s)'s intellectual property rights, are
> protected. Copies of abstracts must be provided to DCP for forwarding
> to Collaborator(s) for courtesy review as soon as possible and
> preferably at least three (3) days prior to submission, but in any
> case, prior to presentation at the meeting or publication in the
> proceedings. Press releases and other media presentations must also be
> forwarded to DCP prior to release. Copies of any manuscript, abstract,
> and/or press release/ media presentation should be sent to:

Head, DCP Protocol Information Office

6130 Executive Boulevard, Room 2050

Rockville, MD 20852

E-mail: <NCI_DCP_PIO@mail.nih.gov>

> The Protocol Information Office will forward manuscripts to the DCP
> Project Officer for distribution to the Collaborator(s). No
> publication, manuscript or other form of public disclosure shall
> contain any of Collaborator's confidential/proprietary information.

13. **STATISTICAL CONSIDERATIONS**

    **13.1 Study Design/Endpoints**

> *This section provides a data analysis plan that is logical and
> appropriate for endpoints selected. Plan does not introduce bias
> through exclusion of randomized participants from analysis (i.e., the
> intent --to-treat approach is used). Clinical relevance of the results
> as well as statistical significance is discussed. Methods of computing
> confidence intervals for endpoints are described. Size of expected
> intervals is indicated. State any assumptions underlying validity,
> note if they are testable, and if so, specify the method of testing.*
>
> *Please specify the study design and primary endpoints. The design
> should consider early testing for sufficiently discouraging results
> (e.g., interim analysis). For the primary endpoint, indicate both the
> range of true values sufficiently promising to justify further testing
> of the agent (e.g., **true** response rate of at least 20%) and a
> range of values sufficiently discouraging to justify no further
> testing of the agent (e.g., **true** response rate no greater than
> 5%). Define the decision rule for declaring the agent promising based
> on the **observed value** of the primary endpoint. Give the
> probability of a positive result, given that the true value falls
> within the promising range, and the probability of a negative result
> (along with the probability of early negative termination), given that
> the true value falls within the discouraging range.*

2.  **Sample Size/Accrual Rate**

> *Please specify the planned sample size and accrual rate (e.g.,
> participants/month). Total sample size (including gender and minority
> considerations) and sampling strategy are described and justified for
> testing the primary and secondary hypotheses. Power calculations for
> proposed sample size and endpoints are presented. For comparative
> studies, differences to be detected are clearly stated and justified
> with pilot or published data.*

**13.3 Randomization and Stratification**

> *Methods for randomization and stratification are described and
> justified. Blocking and/or other techniques used to balance
> intervention assignments are described completely. Indicate whether
> interim analysis and efficacy determination will be done for each
> stratum individually.*

**13.4 Primary Endpoint(s)**

*Appropriate endpoints are selected and analysis methods are described.
May reference Section 8.1*

5.  **Secondary Endpoint(s)**

    *If secondary endpoints are included in this study, please specify
    how they will be analyzed. In particular*

*brief descriptions should be given of analyses of pharmacokinetic,
biologic, and correlative laboratory*

*endpoints.*

**13.6 Reporting and Exclusions**

> *Definition of compliance is clearly stated. Non-compliance is
> sufficiently addressed. Particular consideration is given to dropouts,
> drop-ins, and lost-to-follow up. Handling of missing data or data from
> non-compliers is described. Any methods used to impute missing data
> should be described.*

**13.7 Evaluation of Toxicity**

> All participants will be evaluable for toxicity from the time of their
> first dose of *[\[Study Agent\]]{.underline}* .

8.  **Evaluation of Response**

*All participants included in the study must be assessed for response to
intervention, even if there are major protocol deviations or if they are
ineligible.*

> *All of the participants who met the eligibility criteria (with the
> possible exception of those who did not receive study agent) will be
> included in the main analysis*. *All conclusions regarding efficacy
> will be based on all eligible participants.*

Subanalyses may be performed on the subsets of participants, excluding
those for whom major protocol deviations have been identified (e.g.,
early death due to other reasons, early discontinuation of intervention,
major protocol violations, etc.). However, subanalyses may not serve as
the basis for drawing conclusions concerning efficacy, and the reasons
for excluding participants from the analysis should be clearly reported.
For all measurements of response, the 95% confidence intervals should
also be provided.

**13.9 Interim Analysis**

If relevant to the study agent and study design, provide a plan for
interim analysis and stopping rules.

Include plans for monitoring the progress of the trial to implement
early termination.

**13.10 Ancillary Studies**

*Address the following, as appropriate:*

-   *If known, indicate the prevalence of the marker*

-   *Specify how any cut points will be determined*

-   *Specify the statistical power of the correlative study for the
    endpoint chosen*

-   *If relevant, indicate what corrections will be made for multiple
    comparisons*

-   *If appropriate, indicate relevant clinical endpoint, and a plan for
    how this endpoint will be correlated with the target(s) or
    marker(s).*

14. **ETHICAL AND REGULATORY CONSIDERATIONS**

    1.  **Form FDA 1572**

> Prior to initiating this study, the Protocol Lead Investigator at the
> Lead or Participating Organization(s)will provide a signed Form FDA
> 1572 stating that the study will be conducted in compliance with
> regulations for clinical investigations and listing the investigators,
> at each site that will participate in the protocol.

2.  **Other Required Documents**

    1.  Signed and dated current (within two years) CV or biosketch for
        all investigators listed on the Form FDA 1572 for the Lead
        Organization and all Participating Organizations.

    2.  Current medical licenses for all investigators listed on Form
        FDA 1572 for the Lead Organization and all Participating
        Organizations.

    3.  Lab certification (e.g., CLIA, CAP) and lab normal ranges for
        all labs listed on Form FDA 1572 for the Lead Organization and
        all Participating Organizations.

    4.  IRB Membership list/letter from IRB for the Lead Organization
        and all Participating Organizations.

    5.  Documentation of training in "Protection of Human Research
        Subjects" for all investigators listed on the FDA Form 1572 for
        the Lead Organization and all Participating Organizations.

    6.  Documentation of Federalwide Assurance (FWA) number for the Lead
        Organization and all Participating Organizations.

    7.  Signed receipt of Investigator Brochure

    8.  Delegation of Responsibility form

    9.  FDA Form 3455 Financial Disclosure Form

3.  **Institutional Review Board Approval**

> Prior to initiating the study and receiving agent, the Investigators
> at the Lead Organization and the Participating Organization(s) must
> obtain written approval to conduct the study from the appropriate IRB.
> Should changes to the study become necessary, protocol amendments will
> be submitted to the DCP PIO according to DCP Amendment Guidelines. The
> DCP-approved amended protocol must be approved by the IRB prior to
> implementation.

4.  **Informed Consent**

> All potential study participants will be given a copy of the
> IRB-approved Informed Consent to review. The investigator will explain
> all aspects of the study in lay language and answer all questions
> regarding the study. If the participant decides to participate in the
> study, he/she will be asked to sign and date the Informed Consent
> document. The study agent(s) will not be released to a participant who
> has not signed the Informed Consent document. Subjects who refuse to
> participate or who withdraw from the study will be treated without
> prejudice.
>
> Participants must be provided the option to allow the use of blood
> samples, other body fluids, and tissues obtained during testing,
> operative procedures, or other standard medical practices for further
> research purposes. *If applicable, statement of this option may be
> included within the informed consent document or may be provided as an
> addendum to the consent. A Model Consent Form for Use of Tissue for
> Research is available through a link in the DCP website.*
>
> Prior to study initiation, the informed consent document must be
> reviewed and approved by NCI, DCP, the Consortium Lead Organization,
> and the IRB at each Organization at which the protocol will be
> implemented. Any subsequent changes to the informed consent must be
> approved by NCI, DCP, the Consortium Lead Organization's IRB, and then
> submitted to each organization's IRB for approval prior to initiation.

**14.5 Submission of Regulatory Documents**

> All regulatory documents are collected by the Consortia Lead
> Organization and reviewed for completeness and accuracy. Once the
> Consortia Lead Organization has received complete and accurate
> documents from a participating organization, the Consortium Lead
> Organization will forward the regulatory documents to the DCP
> Regulatory Contractor:
>
> [Paper Document/CD-ROM Submissions:]{.underline}
>
> Manager, Regulatory Affairs
>
> CCS Associates
>
> 2005 Landings Drive
>
> Mountain View, CA  94043
>
> Phone: 650-691-4400
>
> Fax: 650-691-4410
>
> [E-mail Submissions]{.underline}:
>
> <regulatory@ccsainc.com>
>
> Regulatory documents that do not require an original signature may be
> sent electronically to the Consortium Lead Organization for review,
> which will then be electronically forwarded to the DCP Regulatory
> Contractor.
>
> **14.6 Other**
>
> This trial will be conducted in compliance with the protocol, Good
> Clinical Practice (GCP), and the applicable regulatory requirements.

15. **Financing, Expenses, and/or Insurance**

> *The protocol should describe any expenses incurred by the study
> participant and/or their insurance carrier. This includes any injuries
> the participant may have related to their participation in the study.*

**REFERENCES**

*Please provide the citations for all publications referenced in the
text.*

Informed Consent Template and Instructions for Use in Chemoprevention
Clinical Trials

(Based on the NCI treatment consent template, 2006 update)

**[Use of the NCI Informed Consent Template (IC) for Chemoprevention
Trials:]{.underline}**

*\"The use of the DCP Chemoprevention IC Template is required. Adequate
written justification must be provided by the PI if the Chemoprevention
IC Template is not followed either in full or in part.\"*

**GENERAL INSTRUCTIONS:**

\**The comments for authors and investigators are instructional and
should not be included in the informed consent form given to the
prospective research participant.*

> [**COMMENTS FOR INFORMED CONSENT AUTHORS:**]{.underline}

-   Model text is in **bold**. It is recommended that the **bold** text
    be retained, if appropriate, when adapting the template to a
    specific protocol.

-   Instructions and examples are in *\[italics\]*.

-   A blank line, \_\_\_\_\_\_\_\_\_\_, indicates that the local
    investigator should fill in the appropriate information before the
    document is reviewed with the prospective participant.

-   The term "study doctor" is used throughout this template because in
    general the Principal Investigator of a chemoprevention trial is a
    physician. If this template is used for a trial where the Principal
    Investigator is not a physician, another appropriate term should be
    used instead.

-   For Phase I studies, the Principal Investigator may be a PhD.
    However, as per DCP policy, the study must have a physician
    designated as a responsible medical investigator.

-   The template date in the footer refers to the approval date for this
    template only and should not be included in the informed consent
    form given to the prospective research participant.

> [**COMMENTS FOR LOCAL INVESTIGATORS:**]{.underline}

-   The goal of the informed consent process is to provide people with
    sufficient information for making informed choices. The informed
    consent document summarizes the clinical study and the individual\'s
    rights as a research participant. It serves as a starting point for
    the necessary exchange of information between the investigator and
    potential research participant. This template is only one part of
    the larger process of informed consent. To learn more about informed
    consent, review the "Recommendations for the Development of Informed
    Consent Documents for Cancer Clinical Trials," by the

> Comprehensive Working Group on Informed Consent in Cancer Clinical
> Trials for the National Cancer Institute. The Web site for this
> document is located at:

-   <http://www.cancer.gov/clinicaltrials/understanding/simplification-of-informed-consent-docs>

-   An NCI pamphlet explaining chemoprevention clinical trials is
    available. The pamphlet is entitled, "Taking Part in Clinical
    Trials: Cancer Prevention Studies: What Participants Need to Know."
    This pamphlet may be ordered on the NCI Web site:
    <https://cissecure.nci.nih.gov/ncipubs/details.asp?pid=149>

> or by calling 1-800- 4**-** CANCER (1-800-422-6237) to request a free
> copy.

-   Optional feature for Local Investigators: Reference and attach drug
    sheets, pharmaceutical information for the public, or other material
    on risks. Check with your local IRB regarding review of additional
    materials.

\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*

Study Title: *insert title here*

**Introduction**

**This is a clinical trial, a type of research study. Your study doctor
will explain the clinical trial to you. Clinical trials include only
people who choose to take part in the research. Please take your time to
make your decision about volunteering. You may discuss your decision
with your friends and family. You can also discuss this study with your
health care team. If you have any questions, you can ask your study
doctor for more of an explanation. You should only agree to participate
in this study when you are comfortable enough with the information so
that you can make an informed decision about joining.**

*For use when applicable*.

**You are being asked to take part in this study because you are at
increased risk for \_\_\_\_\_\_\_\_ cancer.** *\[Reference and attach
information about the type of cancer and eligibility requirements, if
desired.\]*

Why is this study being done?

**The purpose of this study is to....** *\[Limit explanation to why
study is being done. Explain in 1-2 sentences. Some examples are
provided.\]*

*\[Example: Phase 1 study\]*

*Test the safety of \[drug/intervention\] at different dose levels. We
want to find out what effects, good and/or bad, it has on you and your
risk of \_\_\_\_\_\_\_ cancer.*

*\[Example: Phase 2 study\]*

*Find out what effects, good and/or bad, \[drug/intervention\] has on
you and your risk of \_\_\_\_\_\_\_ cancer.*

*\[Example: Phase 3 study\]*

*Compare the effects, good and/or bad, of \[drug/intervention\] with
\[currently-used drug/intervention or placebo\] on you and your risk of
\_\_\_\_\_\_\_\_ cancer to find out which is better. In this study, you
will get either the \[drug/intervention\] or the \[currently-used
drug/intervention or placebo\]. You will not get both. \[Explain in 1-2
sentences. Examples are: "Currently there is no effective way to prevent
this type of cancer in people at increased risk," or, "We do not know
which of these two commonly used drugs is better."\]*

How many people will take part in the study?

**About** *\[state total target accrual goal here\]* **people will take
part in this study.**

What will happen if I take part in this research study?

\[If appropriate, list tests and procedures and their frequency under
the categories below. Include whether the participant will be at home,
in the hospital, or in an outpatient setting.\]

[**Before you begin the study ...**]{.underline}

**You will need to have the following exams, tests or procedures to find
out if you can be in the study. These may be a part of regular care for
someone at increased risk for \_\_\_\_\_\_\_\_ cancer. If you have had
some of them recently, they may not need to be repeated. This will be up
to your study doctor.**

-   *\[List tests and procedures as appropriate. Use bulleted format.\]*

[**During the study ...**]{.underline}

**If the exams, tests and/or procedures show that you can be in the
study, and you choose to take part, then you will need the following
tests and procedures.**

*\[List tests and procedures as appropriate. Use bulleted format.\]*

These tests and procedures may be part of regular care for someone at
increased risk for \_\_\_\_\_\_\_\_ cancer. They may be done more often
because you are in this study.

-   *\[List tests and procedures as appropriate. Use bulleted format.
    Omit this section if no tests or procedures are being done more
    often than usual.\]*

**You will need these tests and procedures that are either being tested
in this study or being done to see how the study is affecting your
body.**

-   *\[List tests and procedures as appropriate. Use bulleted format.
    Omit this section if no tests or procedures are being tested in this
    study or required for safety monitoring.\]*

*\[For randomized studies:\]* **You will be "randomized" into one of the
study groups described below. Randomization means that you are put into
a group by chance.**

**A computer program will place you in one of the study groups. Neither
you nor your doctor can choose the group you will be in. You will have
an** *\[equal/one in three/etc.\]* **chance of being placed in any
group.**

> **If you are in group 1 (often called \"Arm A\") *...*** *\[Explain
> what will happen for this group.\]*
>
> **If you are in group 2 (often called \"Arm B\")...** *\[Explain what
> will happen for this group.\]*
>
> *\[For studies with more than two groups, an explanatory paragraph
> containing the same type of information should be included for each
> group.\]*
>
> *\[NOTE: Specify how subjects will take the study agent (times/day,
> dosage, and route of administration. List all paperwork (i.e.,
> diaries, questionnaires, etc.) that the participant will be asked to
> complete. List specimens to be collected, including frequency and
> amount.\]*

[**When I am finished taking** \[drugs or
intervention\]**...**]{.underline}

*\[Explain the follow-up requirements, tests, procedures, exams, etc.
required, including the timing of each.\]*

*\[Optional Feature: In addition to the required narrative explanation
found in the preceding text, a [simplified]{.underline} calendar (study
chart) or schema (study plan) may be inserted here. Instructions for
reading the calendar or schema should be included. See examples.\]*

# [Study Plan (*Example)*]{.underline}

**You will receive** \[drug(s) or intervention\] **every** \[insert
appropriate number of days or weeks\] **in this study. The study
calendar below shows what will happen to you during the study.**

###### 

###### 

###### [Study Calendar *(Example)*]{.underline}

######### Day What you do

  ---------- -------------------------------------------------------------
  ­Two days   Get required study blood tests.
  before     
  starting   
  study drug 

  First day  Begin taking \_\_\_\_\_\_ once a day. Keep taking \_\_\_\_\_
  of taking  until the end of study, unless told to stop by your health
  study drug care team. Begin study diary.

  Day 8 of   Complete Quality of Life Questionnaire.
  the study  

  Day 28     Return to clinic for blood tests. Bring diary and
             questionnaire. Also bring your pill bottle and any pills that
             you did not use, or bring the empty pill bottle if you used
             them all.
  ---------- -------------------------------------------------------------

##  {#section-5 .unnumbered}

# [Study Flow Chart *\[Example\]*]{.underline}

**Another way to find out what will happen to you during the study is to
read the study flow chart below. Start reading at the top and read down
the list, following the lines and arrows.**

**↓**

How long will I be in the study?

**You will be asked to take** *\[drugs or intervention\]* **for**
*\[months, weeks\]. \[When appropriate, state that the study will
involve long-term follow-up and specify time frames and requirements of
long-term follow-up.\]*

#### Can I stop being in the study?

**Yes. You can decide to stop at any time. Tell the study doctor if you
are thinking about stopping or decide to stop. He or she will tell you
how to stop safely.**

**If you decide to stop taking the study drug, you may still participate
in other parts of the study. You may be asked if we can still use your
medical information. You can also decide that you do not want us to use
your information.**

The study doctor may stop you from taking part in this study at any time
if he/she believes stopping is in your best interest; if you do not
follow the study rules; or if the study itself is stopped.

What side effects or risks can I expect from being in the study?

**You may or may not have side effects while on the study. Everyone
taking part in the study will be watched carefully for any side effects.
However, doctors don't know all the side effects that may happen. Side
effects may be mild or very serious. Your health care team may give you
medicines to help lessen side effects. Many side effects go away soon
after you stop taking the** *\[drug(s) or intervention\]***. In some
cases, side effects can be serious, long lasting, or may never go
away.** *\[This next sentence should be included if appropriate.*
**There may also be the risk of death.***\]*

*You should talk to your study doctor about any side effects that you
have while taking part in the study.*

**Risks and side effects related to the** *\[procedures, drugs,
interventions, please separate by category\]* **include those which
are:**

**[Likely]{.underline}** e.g. *occurring in [greater]{.underline} than
20% of participants*

-   
-   
-   
-   

**[Less Likely]{.underline}** e.g. *occurring in [less]{.underline} than
or equal to 20% of participants*

-   
-   
-   
-   

**[Rare but Serious]{.underline}** e.g. *occurring in [less]{.underline}
than or equal to 2-3% of participants*

-   
-   
-   

*\* Notes for consent form authors regarding the presentation of risks
and side effects:*

-   *Using a bulleted format, list risks and side effects related to the
    investigational aspects of the trial. Side effects of supportive
    medications should not be listed unless they are mandated by the
    study.*

-   *List by regimen the physical and nonphysical risks and side effects
    of participating in the study in three categories: 1. "likely"; 2.
    "less likely"; 3. "rare but serious".*

-   *There is no standard definition of "likely" and "less likely". As a
    guideline, "likely" can be viewed as occurring in greater than 20%
    of participants and "less likely" in less than or equal to 20% of
    participants. However, this categorization should be adapted to
    specific study agents by the principal investigator*

-   *In the "likely" and "less likely" categories, identify those side
    effects that may be "serious". "Serious" is defined as side effects
    that may require hospitalization or may be irreversible, long-term,
    life threatening or fatal.*

-   *Side effects that occur in less than 2-3% of participants do not
    have to be listed unless they are serious, and should then appear in
    the "rare but serious" category.*

-   *Physical and nonphysical risks and side effects should include such
    things as psychological effects and/or the inability to work.
    Whenever possible, describe side effects by how they make a
    participant feel, for example, "Loss of red blood cells, also called
    anemia, can cause tiredness, weakness and shortness of breath."*

-   *For some investigational drugs/intervention there may be side
    effects that have been noted during administration but there is not
    enough data available to determine if the side effect is related to
    the drug/intervention/device. Because some local Institutional
    Review Boards (IRBs) request to be informed of these possible side
    effects, this information, when available, is provided to the study
    chair. Inclusion of this information in the informed consent
    document is not mandatory. However, if included, these side effects
    should be listed under a separate category titled "Side effects
    reported by participants, but not proven to be caused by
    (drug/intervention/device)". Side effects in this category do not
    have to be labeled as "likely", "less likely" or "rare but serious"
    and should not be repeated here if they appear in a previous
    category. Similar to the other categories, these side effects should
    be listed in a bulleted format.\]*

**Reproductive risks: You should not become pregnant or father a baby
while on this study because the drugs in this study can affect an unborn
baby. Women should not breastfeed a baby while on this study. It is
important you understand that you need to use birth control while on
this study. Check with your study doctor about what kind of birth
control methods to use and how long to use them. Some methods might not
be approved for use in this study. For more information about risks and
side effects, ask your study doctor.**

**Effects of other drugs you may be taking:**

**It is important to tell the doctor or study staff if you are taking
any prescription or over the counter drugs or herbal supplements. We
will need this information to make sure that there is no interaction
with the study agent.**

**You may be asked to avoid donating blood during and for one month
after you stop taking a study drug.**

Are there benefits to taking part in the study?

**Taking part in this study may or may not make your health better.
While doctors hope that the** *\[drug, intervention\]* **will be useful
in cancer prevention, there is no proof of this yet. We do know that the
information from this study will help doctors learn more about**
*\[drug, intervention\]* **as an agent in cancer prevention. This
information could help improve the public health.**

**What other choices do I have if I do not take part in this study?**

Your other choices may include:

\[*If appropriate*: You may get study drugs at this center and other
centers even if you do not take part in the study.\] **Please talk to
your regular doctor about these and other options.**

*\[Additional bullets should include, when appropriate, alternative
specific procedures or interventions.\]*

### Will my medical information be kept private? 

We will do our best to make sure that the personal information in your
medical record will be kept private. However, we cannot guarantee total
privacy. Your personal information may be given out if required by law.
If information from this study is published or presented at scientific
meetings, your name and other personal information will not be used.

**Organizations that may look at and/or copy your medical records for
research, quality assurance, and data analysis include:**

-   *\[List relevant organizations, for example study sponsor(s),
    pharmaceutical company collaborators, local IRBs, and other
    institutions or their representatives responsible for monitoring the
    study.\]*

-   **The National Cancer Institute (NCI) and other government agencies,
    such as the Food and Drug Administration (FDA), involved in keeping
    research safe for people.**

*\[Note to Local Investigators: The NCI has recommended that* *Privacy
Rule regulations enacted under the Health Insurance Portability and
Accountability Act of 1996 (HIPAA) be addressed by the local
institution. The regulations may or may not be included in the informed
consent form depending on local institutional policy.\]*

What are the costs of taking part in this study?

Taking part in this study may lead to added costs to you or your
insurance company. Please ask about any expected added costs or
insurance problems.

*\[If applicable, inform the participant of any tests, procedures or
agents for which there is no charge. The explanation, when applicable,
should clearly state that there are charges resulting from performance
of the test that will be billed to the participant and/or health
plan.\]*

You will not be paid for taking part in this study.

*For more information on clinical trials and insurance coverage, you can
visit the National Cancer Institute's Web site at:*

<http://www.cancer.gov/clinicaltrials/learning/insurance-coverage>

*You can print a copy of the "Clinical Trials and Insurance Coverage"
information from this Web site.*

*Another way to get the information is to call 1-800-4-CANCER
(1-800-422-6237) and ask them to send you a free copy.*

What happens if I am injured because I took part in this study?

**It is important that you tell your study doctor,
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** *\[investigator's name(s)\],*
**if you feel that you have been injured because of taking part in this
study. You can tell the doctor in person or call him/her at
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** *\[telephone number\].*

You can request medical treatment if you are injured as a result of
taking part in this study. You and/or your health plan will be charged
for this treatment. The study will not pay for medical treatment.

#### What are my rights if I take part in this study?

Taking part in this study is your choice. You may choose either to take
part or not to take part in the study. If you decide to take part in
this study, you may leave the study at any time. No matter what decision
you make, there will be no penalty to you and you will not lose any of
your regular benefits. Leaving the study will not affect your medical
care. You can still get your medical care from the institution
conducting the study.

We will tell you about new information or changes in the study that may
affect your health or your willingness to continue in the study.

**In the case of injury resulting from this study, you do not lose any
of your legal rights to seek payment by signing this form or release the
institution from liability for negligence.**

### Who can answer my questions about the study?

**You can talk to your study doctor about any questions or concerns you
have about this study. Contact your study doctor
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** *\[name(s)\]* **at
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** *\[telephone number\].*

For questions about your rights while taking part in this study, call
the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ **\[name of
center\]** Institutional Review Board (a group of people who review the
research in order to protect your rights) at
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ **(telephone number). \[Note to
Local Investigator: Contact information for participant representatives
or other individuals in a local institution who are not on the IRB or
research team but take calls regarding clinical trial questions can be
listed here.\]**

*\[If applicable to the protocol:\]*

**Please note: This section of the informed consent document is about
additional research studies that are being done with people who are
taking part in the main study. You may take part in these additional
studies if you want to. You can still be a part of the main study even
if you say "no" to taking part in any of these additional studies.**

**You can say "yes" or "no" to each of the following studies. Please
mark your choice for each study.**

*\[Insert information about companion studies here. Provide yes/no
options at each decision point. Include information on the average
length of time required to complete questionnaires. The following
studies are included as examples, and therefore are written with
italicized font. Any text provided for participants should use the same
non-italicized font as used for the rest of the informed consent
document.\]*

*\[Example: Quality of Life study\]*

######## **Quality of Life Study**

We want to know your view of how your life has been affected by the use
of this chemoprevention agent. This "Quality of Life" study looks at how
you are feeling physically and emotionally during your time on this
study.

*This information will help doctors better understand what effects the
chemoprevention agents are having. In the future, this information may
help patients and doctors as they decide which medicines to use to
prevent cancer*.

*You will be asked to complete 3 questionnaires: one on your first
visit, one 6 months later, and the last one 12 months after your first
visit. It takes about 15 minutes to fill out each questionnaire.*

*If any questions make you feel uncomfortable, you may skip those
questions and not give an answer.*

*If you decide to take part in this study, the only thing you will be
asked to do is fill out the three questionnaires. You may change your
mind about completing the questionnaires at any time.*

*Just like in the main study, we will do our best to make sure that your
personal information will be kept private.*

*Please circle your answer.*

> *I choose to take part in the Quality of Life Study. I agree to fill
> out the three Quality of Life Questionnaires.*
>
> *YES NO*

*\[Example: Use of Tissue for Research\]*

*\[The following example of tissue consent has been taken from the NCI
Cancer Diagnosis Program's model tissue consent form found at the
following Web site:*

***<http://www.cancerdiagnosis.nci.nih.gov/specimens/model.pdf>.***

*Educational booklet on provision of tissue for research:*

[*https://cissecure.nci.nih.gov/ncipubs/details.asp?pid=1324*](https://cissecure.nci.nih.gov/ncipubs/details.asp?pid=1324)

######## **Consent Form for Use of Body Tissue for Research**

***About UsingYour Body Tissue for Research***

*You are going to have a biopsy as part of the main study. Your doctor
will remove some body tissue to do some tests.*

*We would like to keep some of the tissue that is left over for future
research. If you agree, this tissue will be kept and may be used in
research to learn more about cancer and other diseases. Please read the
information sheet called \"How is Tissue Used for Research\" to learn
more about tissue research.*

*Your tissue may be helpful for research whether you do or do not have
cancer. The research that may be done with your tissue is not designed
specifically to help you. It might help people who have cancer and other
diseases in the future.*

*Reports about research done with your tissue will not be given to you
or your doctor. These reports will not be put in your health record. The
research will not have an effect on your care.*

***Things For You To Think About***

*The choice to let us keep the left over tissue for future research is
up to you. No matter what you decide to do, it will not affect your
care.*

*If you decide now that your tissue can be kept for research, you can
change your mind at any time. Just contact us and let us know that you
do not want us to use your tissue. Then any tissue that remains will no
longer be used for research.*

*In the future, people who do research may need to know more about your
health. While the \[research clinic name\] may give them reports about
your health, it will not give them your name, address, phone number, or
any other information that will let the researchers know who you are.*

*Sometimes tissue is used for genetic research (about diseases that are
passed on in families). Even if your tissue is used for this kind of
research, the results will not be put in your health records.*

*Your tissue will be used only for research and will not be sold. The
research done with your tissue may help to develop new products in the
future.*

***Benefits***

*The benefits of research using tissue include learning more about what
causes cancer and other diseases, how to prevent them, and how to treat
them.*

***Risks***

*The greatest risk to you is the release of information from your health
records. We will do our best to make sure that your personal information
will be kept private. The chance that this information will be given to
someone else is very small.*

***Making Your Choice***

*Please read each sentence below and think about your choice. After
reading each sentence, circle \"Yes\" or \"No\". If you have any
questions, please talk to your doctor or nurse, or call our research
review board at IRB\'s phone number.*

*No matter what you decide to do, it will not affect your care.*

*1. My tissue may be kept for use in research to learn about, prevent,
or treat cancer.*

  -------------------------------------- --------------------------------
  *Yes*                                  *No*

  -------------------------------------- --------------------------------

*2. My tissue may be kept for use in research to learn about, prevent or
treat other health problems (for example: diabetes, Alzheimer\'s
disease, or heart disease).*

  -------------------------------------- --------------------------------
  *Yes*                                  *No*

  -------------------------------------- --------------------------------

*3. Someone may contact me in the future to ask me to take part in more
research.*

  ----------------------------------------- -----------------------------
  *Yes*                                     *No*

  ----------------------------------------- -----------------------------

Where can I get more information?

**You may call the National Cancer Institute\'s Cancer Information
Service at:**

> **1-800-4-CANCER (1-800-422-6237)** or **TTY: 1-800-332-8615**

**You may also visit the NCI Web site at**
[**http://cancer.gov/**](http://cancer.gov/)

-   **For NCI's clinical trials information, go to:
    <http://cancer.gov/clinicaltrials/>**

-   **For NCI's general information about cancer, go to
    http://cancer.gov/cancertopicsinfo**

**You will get a copy of this form. If you want more information about
this study, please ask the study doctor.**

Signature

**I have been given a copy of all \_\_\_\_\_** *\[insert total of number
of pages\]* **pages of this form. I have read it or it has been read to
me. I understand the information and have had my questions answered. I
agree to take part in this study.**

######### Participant \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

**Date
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**

Template Revisions: 3/14/07; 7/02/2007; 12/18/2008

APPENDIX A

**Performance Status Criteria**

  ------------- -------------------------- ------------- ----------------------------
  **ECOG                                   **Karnofsky   
  Performance                              Performance   
  Status                                   Scale**       
  Scale**                                                

  Grade         Descriptions               Percent       Description

  0             Normal activity. Fully     100           Normal, no complaints, no
                active, able to carry on                 evidence of disease.
                all pre-disease                          
                performance without                      
                restriction.                             

                                           90            Able to carry on normal
                                                         activity; minor signs or
                                                         symptoms of disease.

  1             Symptoms, but ambulatory.  80            Normal activity with effort;
                Restricted in physically                 some signs or symptoms of
                strenuous activity, but                  disease.
                ambulatory and able to                   
                carry out work of a light                
                or sedentary nature (e.g.,               
                light housework, office                  
                work).                                   

                                           70            Cares for self, unable to
                                                         carry on normal activity or
                                                         to do active work.

  2             In bed \<50% of the time.  60            Requires occasional
                Ambulatory and capable of                assistance, but is able to
                all self-care, but unable                care for most of his/her
                to carry out any work                    needs.
                activities. Up and about                 
                more than 50% of waking                  
                hours.                                   

                                           50            Requires considerable
                                                         assistance and frequent
                                                         medical care.

  3             In bed \>50% of the time.  40            Disabled, requires special
                Capable of only limited                  care and assistance.
                self-care, confined to bed               
                or chair more than 50% of                
                waking hours.                            

                                           30            Severely disabled,
                                                         hospitalization indicated.
                                                         Death not imminent.

  4             100% bedridden. Completely 20            Very sick, hospitalization
                disabled. Cannot carry on                indicated. Death not
                any self-care. Totally                   imminent.
                confined to bed or chair.                

                                           10            Moribund, fatal processes
                                                         progressing rapidly.

  5             Dead.                      0             Dead.
  ------------- -------------------------- ------------- ----------------------------

**A-1**