NU Study Number:Will be assigned by SRC Coordinator

Other Study Number:Other reference numbers used by external collaborators (if applicable)

***DELETE THIS PAGE FROM FINAL VERSION***

Protocol Template Instructions

This template has been created to assist in the development of an investigator-initiated clinical trial protocol.It is not mandatory that you follow the exact order presented in this template (although this is the preferred format for studies that will utilize services of the Clinical Research Office). However, all the information contained in this template must be present, in some format, in your final protocol.

The sections in BLACK are standard/required language for studies under the purview of the Robert H. Lurie Comprehensive CancerCenter and should be included in your protocol and/or revised as needed to reflect the specifics of your trial. In some cases, alternate language choices are included and may be more appropriate.

Please note that a Letter of Intent (LOI) must be submitted to the Lurie Cancer Center’s Scientific Review Committee (SRC) for all Northwestern University interventional investigator-initiated trials [IITs] prior to full protocol submission. Please refer to additional instructions which may be included in the SRC approval letter for your LOI, as these may provide guidance as to what language is required in your protocol.

The sections in BLUE provide examples and/or instructions, and details should be modified to fit your specific trial. You may RENAME sections (if appropriate) and/or DELETE any sections that do not apply. The final protocol document should not contain any BLUE text.

CONFIDENTIAL

This material is the property of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Do not disclose or use except as authorized in writing by the study sponsor.

NU Study Number:Will be assigned by SRC Coordinator

Other Study Number:Other reference numbers used by external collaborators (if applicable)

Study Title

Title should include studyphase, design descriptors(e.g., randomized, double-blind, placebo-controlled, multi-center, etc.), the intervention(s), the target population (disease(s)or condition(s) and stage, if appropriate), and the setting (e.g. front-line, adjuvant, etc). Acronyms should be spelled out.

Principal Investigator:Name/Credentials(One person only - may not be a resident/fellow)

Institution/Department or Division

Address

City, State, Zip

Phone:

Fax:

Email

Sub-Investigator(s):For local sub-Is include:

Name

Department/Division(may group individuals together from same)

For external sub-Is include (one per site):

Name/Credentials

Institution

Address

City, State, Zip

Phone:

Fax:

Email

Biostatistician:Name

Email

(May include other contact info if biostatistician is external)

Study Intervention(s):Generic study drug name, followed by marketed name

IND Number:May list “pending” or “TBD” or delete if N/A.

IND Holder:Delete if N/A.

Funding Source: List support (funding or investigational agent) from Industry or other sources (provide grant number, if applicable.)

Version Date:

Coordinating Center:Clinical Research Office

Robert H. Lurie Comprehensive Cancer Center

Northwestern University

676 N. St. Clair, Suite 1200

Chicago, IL 60611

CONFIDENTIAL

This material is the property of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Do not disclose or use except as authorized in writing by the study sponsor.

NU Study Number:Will be assigned by SRC Coordinator

Other Study Number:Other reference numbers used by external collaborators (if applicable)

TABLE OF CONTENTS

LIST OF ABBREVIATIONS

STUDY SCHEMA

1.0STUDY SUMMARY

1.0INTRODUCTION – BACKGROUND & RATIONALE

1.1Disease Background

1.2Intervention Background & Overview

1.3Rationale for the Current Study

1.4Exploratory Studies

2.0OBJECTIVES & ENDPOINTS

2.1Primary Objective & Endpoint

2.2Secondary Objectives & Endpoints

2.3Exploratory Objectives & Endpoints

3.0PATIENT ELIGIBILITY

3.1Inclusion Criteria

3.2Exclusion Criteria

4.0TREATMENT PLAN

4.1Overview

4.2Treatment Administration

4.3Phase I Dose Escalation Scheme

4.4Toxicity Management & Dose Delays/Modifications

4.5Concomitant Medications/Treatments

4.6Other Modalities or Procedures

4.7Duration of Therapy

4.8Duration of Follow Up

4.9Removal of Subjects from Study Treatment and/or Study as a Whole

4.10Patient Replacement

5.0STUDY PROCEDURES

6.0ENDPOINT ASSESSMENT

6.1Definitions

6.2Primary Endpoint

6.3Secondary Endpoints

7.0ADVERSE EVENTS

7.1Adverse Event Monitoring

7.2Definitions & Descriptions

7.3Adverse Event Reporting

8.0DRUG INFORMATION

8.1Agent XXX

9.0CORRELATIVES/SPECIAL STUDIES

9.1Sample Collection Guidelines

9.2Sample Processing, Storage, and Shipment

9.3Assay Methodology

9.4Specimen Banking

10.0STATISTICAL CONSIDERATIONS

10.1Study Design/Study Endpoints

10.2Sample Size and Accrual

10.3Data Analyses Plans

11.0STUDY MANAGEMENT

11.1Institutional Review Board (IRB) Approval and Consent

11.2Amendments

11.3Registration Procedures

11.4Instructions for Participating Sites

11.5Data Management and Monitoring/Auditing

11.6Adherence to the Protocol

11.7Investigator Obligations

11.8Publication Policy

REFERENCES

APPENDICES

1

NU Study Number:Will be assigned by SRC Coordinator

Other Study Number:Other reference numbers used by external collaborators (if applicable)

LIST OF ABBREVIATIONS

It may be helpful to include a list of frequently-used abbreviations. Some examples commonly used in oncology research include:

AE / Adverse Event
ALT / Alanine Aminotransferase
ALC / Absolute Lymphocyte Count
AST / Aspartate Aminotransferase
BUN / Blood Urea Nitrogen
CBC / Complete Blood Count
CMP / Comprehensive Metabolic Panel
CR / Complete Response
CT / Computed Tomography
CTCAE / Common Terminology Criteria for Adverse Events
DLT / Dose Limiting Toxicity
DSMB / Data and Safety Monitoring Board
ECOG / Eastern Cooperative Oncology Group
H&PE / History & Physical Exam
IV (or iv) / Intravenously
MTD / Maximum Tolerated Dose
NCI / National Cancer Institute
ORR / Overall Response Rate or Objective Response Rate
OS / Overall Survival
PBMCs / Peripheral Blood Mononuclear Cells
PD / Progressive Disease
PFS / Progression Free Survival
PO (or p.o.) / Per os/by mouth/orally
PR / Partial Response
SAE / Serious Adverse Event
SD / Stable Disease
SGOT / Serum Glutamic Oxaloacetic Transaminase
SPGT / Serum Glutamic Pyruvic Transaminase
WBC / White Blood Cells

STUDY SCHEMA

The schema should be a diagram or pictorialrepresentation ofyour study design and general treatment plan. For example:

STUDY SUMMARY

Title / Full title of protocol
Short Title / Shortened title(match this to title used it ClinicalTrials.gov)
Version / Include date & amendment number.
Study Design / Study phase & design attributes such as single blind, double blind or open label; randomized, placebo or active placebo control; cross-over design, Simon two-stage, etc.
Study Center(s) / If multi-center, list all projected centers to be involved & indicate who the lead site will be.
Objectives / At a minimum list all primary & secondary objectives (can refer to body of protocol for any exploratory objectives).
Sample Size / Number of subjects projected for the entire study (may specify by phase if phase I/II trial).
Diagnosis Key Eligibility Criteria / Note the main clinical disease state under study and some of the significant inclusion or exclusion criteria (do not list all criteria here)
Treatment Plan / Brief overview of treatment plan including study intervention(s) and dose/route/regimen or other description of therapy (for non-drug or biologic). Also state overall treatment/intervention timeframe. NOTE: If name-brand agent is used in the study, may reference the marketed name in background or drug info section, but should use generic name throughout majority of the protocol.
Statistical Methodology / A very brief description of the main elements of the statistical methodology to be used in the study (sample size and power calculation, brief discussion of primary endpoint analysis).

1.0Introduction – BACKGROUND & RATIONALE

1.1Disease Background

Please provide disease background information particularly relevant to your study, such as incidence, prognosis or current data corresponding to planned endpoints; be specific about the population being studied (e.g. relapsed/refractory disease or previously untreated or those possessing a particular genetic marker, etc). Questions to be addressed may include the current standard of care and any relevant treatment issues or controversies. Please justify why an investigational therapy or approach is warranted.

1.2Intervention Background & Overview

Please provide relevant background information about the study agent(s) or intervention(s) that you are planning to use in the study. Include the following for each intervention:

  • FDA approval status (if applicable).
  • A summary of findings from non-clinical in vitro/in vivo studies that have potential clinical significance including information on mechanism of action, pharmacokinetics and safety. NOTE: This is particularly important for investigational agents, and may not be necessary for commercially available drugs, and/or drugs with sufficient clinical data.
  • A summary from relevant clinical studies (or current clinical use), with focus on those that provide background for your study.
  • Important safety information, such as known toxicities and current or approved doses and regimens.
  • If available (especially for early-phase or first-in-human trials): information on clinical pharmacokinetics, major route(s) of elimination, metabolism of the agent(s) in humans, and any potential for drug interactions.

1.3Rationale for the Current Study

Discuss the reasoning for conducting the study in light of the background information already presented. Specifically, provide rationale for each of the following:

  • The study design being used, including the primary endpoints.
  • The population being studied (particularly if focusing on a subset within the disease population, such as relapsed disease or elderly patients).
  • The treatment plan (particularly if doses and/or regimens are not established or will not follow approved versions).

1.4Exploratory Studies

If applicable, please provide background information to support any exploratory endpoints such as correlative studies; include the biological rationale and hypothesis (if applicable).

2.0OBJECTIVES & endpoints

Please list all Primary, Secondary, and Exploratory objectives of the study (see below for definitions). Number objectives separately. In addition, it is strongly recommended that you have only one primary objective. An overall summary of the goal of the study is fine to include (e.g. “Establish the safety and efficacy of the combination of X and Y in the treatment of Z”), however specific objectives with measurable outcomes should be given to support this broad goal.

For each objective please describe the corresponding endpoint, which is the outcome that is being measured. This includes what will be measured, how, and when. In addition, there are generally 4 levels of specificity that should be included:

Level 1 – Domain or the type of health outcome measure.

Level 2 – Specific tool to measure the domain.

Level 3 – Specific metric to be measured.

Level 4 – Method of aggregation (continuous vs. categorical).

An example of a clearly written objective and endpoint is the following:

The primary objective will be to assess the efficacy of drug ABC on reducing symptoms of depression in patients undergoing chemotherapy. The endpoint will be a change in depression score on the Hamilton Anxiety Rating Scale of ≥ 5 points from baseline to end of treatment with drug ABC (6 weeks).

Level 1: outcome/domain = depression

Level 2: tool = Hamilton Anxiety Rating Scale

Level 3: specific metric = change from baseline to post-treatment (6 week timeframe)

Level 4: aggregation = categorical (will report proportion of patients who achieve a change in

score of ≥ 5 points on the scale)

Other examples of common endpoints and things to consider:

  • Response – often a primary endpoint for phase II trials
  • Specify which criteria will be used (e.g. RECIST, Cheson, iwCLL2008, etc)
  • Specify how it will be reported:
  • By response category (e.g. CR/PR/SD/PD or some combination of these)
  • In terms of time or “duration of response”
  • Survival – often used in phase II or III trials
  • Specify the type (e.g. progression-free or overall survival) and at what timepoint (e.g. indefinitely vs. at 2 years from start of treatment)
  • Safety/toxicity – often used in phase I or II trials
  • Specify what criteria will be used (e.g. NCI CTCAE v 4.0) or if the focus will be on a specific list of adverse events of interest
  • Quality of life – may be a secondary or even exploratory endpoint in any trial
  • Specify the subjective measure that will be used (if it is a tool or survey, briefly describe in background and indicate if it has been validated)

Consider whether or not certain objectives are truly exploratory in nature (such as pharmacokinetics studies, tissue correlatives, etc). It is strongly encouraged to label objectives that are not associated with health outcomes as exploratory.

2.1Primary Objective & Endpoint

2.2Secondary Objectives& Endpoints

2.2.1

2.2.2

2.2.3

2.3Exploratory Objectives & Endpoints

Delete ifnot applicable.

3.0PATIENT ELIGIBILITY

The target population for this study is patients with [insert description]. This will be a [multicenter or single-center]trial conducted at [insert name of site or clinic] of Northwestern University. Remove or revise the following as appropriate: Northwestern University will serve as the lead site and coordinating center for this study. Participating sites will include[list additional sites].

A total of ## subjects will be needed for this trial. Approximately # potentially eligible patients are seen per month, and it is anticipated that at least # per month will be accrued (once all sites are up and running). Potential patients may be referred to the Principal Investigator (PI) at Northwestern University, Dr. [insert name], at (###) ###-####, or to the local PI at each participating site.

Eligibility will be evaluated by the study team according to the following criteria. Eligibility waivers are not permitted. Subjects must meet all of the inclusion and none of the exclusion criteria to be registered to the study. Study treatment may not begin until a subject is registered. Please refer to Section 11 for complete instructions regarding registration procedures.

3.1Inclusion Criteria

Each criterion should include its own number, e.g., 3.1.1, 3.1.2, etc. Inclusion criteria should not contain phrases that are actually meant to exclude patients (e.g. “patients must not have had prior radiation therapy” is actually an exclusion criteria and should be listed in section 3.2 accordingly).

3.1.1Patients must have a [histologically/cytologically/confirmed by imaging or other means]diagnosis of [insert disease name and stage]

3.1.2Patients must have [measurable or evaluable] disease. NOTE: include definition of measurable, if applicable.

3.1.3Include allowed type(s) and amount(s) of prior therapy for this cancer, along with any required washout periods.

3.1.4Patients must be age ≥ 18 years.

3.1.5Patients must exhibit a/an [ECOG, Karnofsky, or other] performance status of [insert values].

3.1.6Patients must have adequate organ and bone marrow function within # days prior to registration,as defined below:(adjust values as appropriate)

  • leukocytes≥ 3,000/mcL
  • absolute neutrophil count≥ 1,500/mcL
  • platelets≥ 100,000/mcl
  • total bilirubinwithin normal institutional limits
  • AST(SGOT)/ALT(SPGT)≤ 2.5 X institutional upper limit of normal (ULN)
  • creatininewithin normal institutional limits
  • May add others…

NOTE: Include any exceptions to the above (such as Gilbert’s Syndrome) and note whether nor not levels may be achieved with transfusion and/or growth factor support.

3.1.7Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (give examples, e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for # days following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the

following criteria:

  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

3.1.8FOCBP must have a negative pregnancy test within # days prior to registration on study.

3.1.9Other study-specific inclusion criteria or baseline parameters that are required for eligibility purposes (such as LVEF, QTc interval, disease-specific criteria, etc).

3.1.10Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.

3.2Exclusion Criteria

Some examples might include…

3.2.1Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are not eligible.

3.2.2Patients may not be receiving any other investigational agents.

3.2.3Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to[study agent(s)] are not eligible.

AND/OR

Patients who have had prior exposure to compounds of similar chemical or biologic composition to [study agent(s)] are not eligible.

3.2.4Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:(edit/remove/add to list as needed)

  • Hypertension (defined as ###/##) that is not controlled on medication
  • Ongoing or active infection requiring systemic treatment
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient’s safety or study endpoints

3.2.5Female patients who are pregnant or nursing are not eligible.

3.2.6Other study specific or disease criteria for exclusion (e.g. certain disease sub-types that are not eligible, patients who are unable to swallow oral medication if the study involves oral agents, etc).

4.0TREATMENT PLAN

As with all sections of this template, please delete sub-sections that do not apply and/or re-name to fit the specifics of your study.

4.1Overview

Give a brief (1-2 paragraphs at most) summary of the treatment plan, including intervention(s), doses/regimens, duration of treatment, and key study time-points(response assessment, futility assessment, transition from phase I to II if a combination study, etc).

4.2Treatment Administration

It may be useful to include a table that summarizes the various interventions prior to giving details:

Treatment Administration Summary
Agent / Premedications / Dose / Route / Schedule / Cycle Length / Supportive Therapies
Drug X / Acetaminophen 650 to 1000 mg every 4 to 6 hours for 3 days prior to Drug X / 300 mg/m2 / IV over 2 hours before Drug Y (day 1 only) / Days 1, 8, and 15 of each cycle / 4 weeks (28 days) / Omeprazole or similar as needed
Drug Y / n/a / 150 mg/m2 / IV 30 min after completion of Drug X (day 1 only) / Day 1 of each cycle / n/a
Drug Z / n/a / 50 mg tablet / PO in the a.m. at least 1 hour before eating / Daily x 3 weeks followed by 1 week break per cycle / Switch to taking 1 hour after eating if vomiting occurs

4.2.1Intervention/Agent A

Describe the intervention in detail, including the following: