WVU Protocol Template
Version Date: 02/2016
PROTOCOL TEMPLATE INSTRUCTIONS
The protocol template is a tool to facilitate protocol development.It is not intended to supersede the role of the Principal Investigator in the authoring and scientific development of the protocol.It contains the “boilerplate” language commonly required to be submitted to the MBRCC PRMC, NIH and external funding agencies. Content may be modified as necessary to meet the scientific aims of the study and development of the protocol.
The BLUE text is meant to provide instructions and examples, please delete the BLUE instructions and examples and replace them with protocol specific designs.
- The main body and appendices of the protocol are attached below. This document provides standard language plus instructions and prompts for information.
- The Protocol and Informed Consent Template documents should be completed, and all documents (including the Appendices) should be submitted to the PRMCor other protocol review committee for review.
- All sections in the Protocol Template should be retained to facilitate rapid review. If not appropriate for a given study, please insert “Not Applicable” after the section number and delete unneeded text.
- Please note that the Protocol Template has built-in styles for Heading Levels 1-3,Level 5 for the Appendix and Normal for body of text. (see image below).
These heading styles will automatically update the Table of Contents (TOC) and convert to Bookmarks in a final PDF protocol document. Please retain the heading styles.
- To update the TOC in your protocol document:
- Right click somewhere in the table of contents, the entire TOC should be highlighted gray
- Click on Update Field
- Choose Update entire table
- Click OK
Please do not edit the TOC manually.
WVUXXXXXX
Version Date:
STUDY NUMBER:WVUXXXXXX
Number will be assigned by Cancer Center at time of PRMC Submission
Protocol Version Date:
STUDY TITLE:Full study title here (600 characters maximum)
PRINCIPAL INVESTIGATOR:A study can only have one Principal Investigator. Principle Investigators much be faculty members.
The Co-PI(s) refer to the physician(s) who will lead the study at non-lead institution(s).
Example: Joint Protocol with Institution Lead
PRINCIPAL INVESTIGATOR:Name of Physician, MD
Department
West Virginia University Cancer Institute
Mary Babb Randolph Cancer Center
1 Medical Center Drive
Morgantown, WV 26506
Telephone including area code
Email address
CO-PI:(if joint protocol)Name of Physician, MD
Department
Institution
Institution address
Telephone including area code
Email address
List co-investigators alphabetically by site in the following order:
Lead Institution
Joint Institution
*If this is a multi-institutional study, the protocol title page should include the name of each participating institution, the investigator responsible for the study at that institution, and his/her telephone # and e-mail address.
CO- INVESTIGATOR:Name of Physician, MD
Department
West Virginia University Cancer Institute
Mary Babb Randolph Cancer Center
1 Medical Center Drive
Morgantown, WV 26506
Telephone including area code
Email address
STATISTICIAN:Name of Statistician, degree
Name of Institution
Street Address
City, State, Zip code
Telephone including area code
Email address
STUDY COORDINATOR:Name of Lead Study Coordinator
Name of Institution
Street Address
City, State, Zip code
Telephone including area code
Email address
SPONSOR:WVU Cancer Institute Mary Babb Randolph Cancer Center / WV Clinical and Translational Institute
SUPPORT/FUNDING:List any support/grants or any funding source (partial or full) here
SUPPLIED AGENT(S):Name of supplied agents and supplier, if applicable
IND #:If applicable
OTHER AGENT(S):Name of other agents
SUMMARY OF CHANGES
Please provide a list of changes from the previous approved version of the protocol starting at IRB approval. This table will remain blank until initial IRB approval. The list shall be a brief overview. When appropriate, a brief justification for the change should be included. This is a running list for the life of the study.
Protocol Date / Section / ChangeInitial IRB approval
Summarize changes to first protocol amendment
1
WVUXXXXXX
Version Date:
STUDY SCHEMA
Please provide a visual schema for the study.
If preferred, a summary or synopsis may be provided.
Protocol Synopsis:
Protocol Number/Title / Assigned protocol number/TitleStudy Phase / Study phase
Brief Background/Rationale / Include:
Why doing this study on this population with this drug.
Incidence/burden
Primary Objective / Primary Endpoint(s)
Endpoints: how it will be measured and at what time point. Do not use “end of study” or “at progression”.
Secondary Objective(s) / Secondary Endpoint(s)
Exploratory Objective(s) / Exploratory Endpoints (s)
This is where exploratory research endpoints will go. For example, gathering preliminary data
Correlative Objective(s) / Correlative Endpoint(s)
This is where correlative study objectives will go. Pharmacokinetics, Pharmacodynamics, and biomarkers, etc.
Sample Size / Number expected to accrue
Age, gender
Disease sites/Conditions / ICD terminology
Interventions / Agent X, route, dose, cycle length, number of cycles
Agent Y, route, dose, cycle length, number of cycles
Abbreviations
MBRCC / Mary Babb Randolph Cancer CenterCRF / Case Report Form
CTRU / Clinical Trials Research Unit
DSTC / Data Safety Toxicity Committee
FDA / Food and Drug Administration
ICF / Informed Consent Form
IRB / Institutional Review Board
PRMC / Protocol Review and Monitoring Committee
SOC / Standard of Care
Please update table with relevant abbreviations used in the protocol
TABLE OF CONTENTS
1.OBJECTIVE
1.1.Primary Objective
1.2.Secondary Objective(s)
1.3.Correlative Objective(s)
2.BACKGROUND
2.1.Background of Study Disease
2.2.Name and Description of Investigational Agent X
2.3.Name and Description of Investigational Agent Y
2.4.Name and description of Other Agent(s) (if applicable)
2.5.Rationale
2.6.Background and rationale of correlative studies
3.STUDY DESIGN
3.1.Study design including dose escalation / cohorts
3.2.Number of Subjects
3.3.Replacement of Subjects
3.4.Expected Duration of Treatment and Subject Participation
4.SUBJECT SELECTION AND REGISTRATION
4.1.Inclusion Criteria
4.2Exclusion Criteria
4.3Inclusion of Women and Minorities
4.2.Registration
5.TREATMENT PLAN AND/OR IMAGING PLAN
5.1.Name of Investigational Agent Administration
5.2.Phase I Dose Escalation
5.3.Definition of Dose-Limiting Toxicity
5.4.Name of Standard of Care (SOC) Agent(s) Administration
5.5.Name of Other Modality(s) or Procedures
5.6.General Concomitant Medications and Supportive Care Guidelines
5.7.Duration of Therapy
5.8.Duration of Follow Up
5.9.Criteria for Removal from Study
6.DOSE DELAYS/DOSE MODIFICATIONS
7.ADVERSE EVENTS
7.1.Definitions
7.2.Adverse Event Evaluation
7.3.Adverse Event Reporting Procedures
7.4.Serious Adverse Event Reporting Procedures
7.5.SAEs and OnCore
7.6.Data Safety and Toxicity Committee
7.7.Data and Safety Monitoring Plan (DSMP)
8.PHARMAPEUTICAL OR IMAGING INFORMATION
8.1.Investigational Agents
8.2.Commercial Agent
9.CORRELATIVE AND SPECIAL STUDIES
9.1.Name of Exploratory or Correlative study #1
9.2.Name of Exploratory or Correlative study#2
10.STUDY PARAMETERS AND CALENDAR
10.1.Study Parameters
10.2.Study Calendar
11.MEASUREMENT OF EFFECT
11.1.Antitumor Effect – Solid Tumors
11.2.Response Criteria
11.3.Antitumor Effect – Hematologic Tumors
11.4.Other Response Parameters
12.DATA REPORTING / REGULATORY CONSIDERATIONS
12.1.Data Reporting
12.2.Regulatory Considerations
13.STATISTICAL CONSIDERATIONS
13.1.Study Design/Endpoints
13.2.Sample Size/Accrual Rate
13.3.Stratification Factors
13.4.Analysis of Secondary Endpoints
13.5.Methods for Analysis
13.6.Safety Analysis
13.7.REFERENCES
14.APPENDICES
Appendix 1
1.OBJECTIVE
Describe the overall objectives and purpose of the study, keeping in mind that objectives must be measurable.
Records to be kept should capture the measurement. Study parameters (calendar) should indicate when captured.
1.1.Primary Objective
It is preferable to have only one primary objective and primary endpoint. What scientific question are you trying to answer?
1.2.Secondary Objective(s)
1.3.Correlative Objective(s)
2.BACKGROUND
2.1.Background of Study Disease
Please provide background, incidence, and treatment information on the study disease.
Please be specific in the title for disease specific studies.
Example: “Advanced Biliary Cancers” versus “Advanced Cancers”
2.2.Name and Description of Investigational Agent X
2.2.1.Preclinical Data
Provide background and brief information for agent X. Include any animal studies, the explanation of the mechanism of action, and any preclinical data about the agent or treatment.
2.2.2.Clinical Data
Summarize the available clinical study data with relevance to the protocol under development. If none is available, include a statement that there is no available clinical research data to date on the investigational product.
2.2.3.Clinical Pharmacokinetics (if applicable)
Add metabolism, molecular formula and classification information here if available.
2.3.Name and Description of Investigational AgentY
Note: Section is repeated for each investigational agent as applicable to protocol.
2.3.1.Preclinical Data
2.3.2.Clinical Data
2.3.3.Clinical Pharmacokinetics
2.4.Name and description of Other Agent(s)(if applicable)
Please provide background information on other agent(s) and/or treatments in this study, including information to support safety issues and the rationale for the proposed starting dose and dose escalation scheme, if applicable.
2.4.1.Preclinical Data
2.4.2.Clinical data
2.4.3.Clinical Pharmacokinetics
2.5.Rationale
Please provide the background and rationale for evaluating this (combination) therapy in this disease. Include the rationale for the proposed starting doses and dose escalation scheme as well as route of administration and dosage period.
2.6.Background and rationale of correlative studies
Please provide the background and rationale for correlative studies and exploratory endpoints.
3.STUDY DESIGN
Please provide an overview of the study design and the rationale for this type of design.
3.1.Study design including dose escalation / cohorts
This section should include: the type of trial design of the study, stages, cohort information, how subjects will be randomized and if there are plans to use a placebo.
3.2.Number of Subjects
Provide the number of subjects that will be included in the study using a sentence format.
Example:Approximately 50 subjects will be enrolled in this trial.
Example if more than one phase:Approximately 50 subjects will be enrolled in this trial. Approximately 15 will be enrolled in the phase I part and 35 in the phase II part.
3.3.Replacement of Subjects
The replacement of subjects is protocol specific and needs to be tailored to the trial.
Example: If Oral Drug is to be taken 21 out of 21 days and this is not met:
Example: If a subject does not take at least 17 doses in the first cycle, the subject will be replaced because he/she has not taken enough drug to confirm safety at that dose level.
3.4.Expected Duration of Treatment and Subject Participation
Please provide a brief summary of the length of treatment period, plus the length of follow up period and any study windows that are applicable. Please provide length of each cycle, minimum and maximum number of cycles. If treatment can continue until disease progression (i.e. no maximum number of cycles), please indicate here. If clinical benefit is not likely until after a certain number of cycles, specify that here.
Treatment duration may be modified per section ___.
4.SUBJECT SELECTION AND REGISTRATION
Each of the criteria in the sections that follow must be met in order for a subject to be considered eligible for this study.Use the eligibility criteria to confirm a subject’s eligibility.
Patient’s Name ______
Medical Record # ______
Research Nurse /
Study Coordinator Signature:______Date ______
Treating Physician [Print] ______
Treating Physician Signature:
______Date ______
4.1.Inclusion Criteria
Inclusion Criteria must describe the subject population that you want to include in the study.
Create a numbered list of criteria applicable to the protocol that subjects must meet to be eligible for study enrollment.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment:
Below are common examples: Edit per protocol
____4.1.1 Subjects must have histologically or cytologically confirmedName of Disease.
Please specify eligible disease(s)/stage(s)/prognostic score(s) as well as if staging is pathological or clinical.
___4.1.2 Subjects must have received (no, no more than X) prior therapies for this disease.
**If applicable, provide guidance on what constitutes a prior line of therapy, how to count prior lines of therapy and breaks in therapy.
____4.1.3 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 ______in combination with ______in subjects ≤18 years of age, children are excluded from this study.”
____4.1.4 Performance status _____[See Appendix __].
Choose one method (not both):
Example: ECOG Performance status ≤ 2
Example: Karnofsky Performance status ≥60%
____4.1.5 Subjects must have normal organ and marrow function as defined below: Add time frame if applicable.
Please review for relevance to the specific study and modify.
Example:
- Hemoglobin ≥ 10.0 g/dl
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Total bilirubin within normal institutional limits
- AST (SGOT) ≤ 2.5 X institutional upper limit of normal
- ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
- Serum Creatinine within normal institutional limits
____4.1.6Please insert other appropriate eligibility criteria.
____4.1.7 Subjects must have the ability to understand and the willingness to sign a written informed consent document.
4.2Exclusion Criteria
Exclusion Criteria must describe the subject population that you do NOT want to include in the study.
Create a numbered list of criteria applicable to the protocol that would exclude a subject from study enrollment.
The presence of any of the following will exclude a subject from study enrollment.
Below are common examples: Edit per protocol or see further examples hyperlinked above.
____4.2.1 Prior treatment toxicities resolved to ≤ GradeX according to NCI CTCAE Version 4.0 (list exceptions, e.g. alopecia, neuropathy, etc).
____4.2.2 Subjects receiving any other investigational agents.
____4.2.3 To be included if applicable to protocol.Suggested text is provided below:
Subjects with untreated brain metastases/CNS diseasewill be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
____4.2.4History of allergic reactions attributed to compounds of similar chemical or biologic composition to AgentX or other agents used in this study.
Please state appropriate exclusion criteria relating to concomitant medications or substances that have the potential to affect the activity or pharmacokinetics of the study agent(s).
____4.2.5 Subjects with uncontrolled intercurrent illnessincluding, 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.
The investigator must state a medical or scientific reason if pregnant or nursing subjects will be excluded from the study.
Suggested text is provided below:
____4.2.6 Pregnant or breastfeeding are excluded from this study because Agent X is Name of Agent Class 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 Agent X, breastfeeding should be discontinued if the mother is treated with Agent X. These potential risks may also apply to other agents used in this study.
____4.2.7Insert other appropriate agent-specific exclusion criteria.
4.3Inclusion of Women and Minorities
Make sure you include the appropriate verbiage for the subject population.
Both men and women of all races and ethnic groups are eligible for this trial.It is the policy of the Mary Babb Randolph Cancer Center to strive for gender and minority patient participation that represents the population of West Virginia in all clinical investigations. Between January 2015and December 2015, 233 patients were enrolled onto clinical trials at the Mary Babb Randolph Cancer Center. Of these patients 55% percent were female and 3% percent were members of minority ethnic groups. It is anticipated that a similar or greater proportion of patients on this study will be female and/or members of ethnic minorities. It is important to recognize that according to the 2014 US Census Bureau (available at that the State of West Virginia minority ethnic group (e.g.,not limited to African American and Hispanic) population is 3.6% Black (national average 13.2%) and 1.5% Hispanic (national average 17.4%). The majority of Black West Virginians live in the central and southern part of the state and Gilmer County is the only county in WV whose Black population approaches the national average.
4.2.Registration
At the point of registration, the study coordinator will complete registration in the OnCore database, including demographic, consent and on-study information.
The patient will be assigned a unique sequence number for the study prior to the initiation of the study treatment.
For those subjects who are consented, but not enrolled, the reason for exclusion must be recorded.
All source documents that support eligibility, signed informed consent/HIPAA and signed eligibility checklist must be available for review and verification by the quality coordinator prior to starting therapy.
If the trial is randomized the method of randomization should be stated as well as the proportion of subjects that will be accrued to each dose level.
Example:Subjects will be assigned to either [Name of Study Agent] or [Name of Study Agent + Name of Study Agent] based on the randomization lists prepared by the WVU MBRCC Biostatistics Core. Randomization will be stratified by: EXAMPLES: performance status (0-1 vs. 2) and smoking status (ever vs. never lifetime). This is a 1:1 randomization.
5.TREATMENT PLAN AND/OR IMAGING PLAN
Describe the treatment regimen planned. If there are different cohorts, label each cohort and appropriate treatment schedule:
- Pre-medications allowed/required/suggested (if applicable)
- Agent(s)
- Dose(s)
- Route of administration
- Treatment schedule
- Treatment duration
Please provide separate regimen descriptions for different treatment groups of subjects as necessary.