A Pilot Feasibility Study of Next Generation Sequencing-Based Stratification of Front Line Treatment of HighGrade Neuroendocrine Carcinoma
Phase: NA
Conditions: Large-Cell Neuroendocrine Carcinoma
Sponsor: Charles Kunos

Document Coversheet 
 
 Study Title: A Pilot Feasibility Study of Next Generation Sequencing-Based Stratification of Front Line 
Treatment of HighGrade Neuroendocrine Carcinoma 
Institution/Site:  
University of Kentucky 
Document (Approval/Update) Date: 
2/14/2023 
NCT Number: 
NCT04452292 
IRB Number 
59128 
Coversheet created: 
4/19/2023 
 
 

PROTOCOL TYPE (VERSION 4)
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Which IRB
Medical
NonMedical
Protocol Process Type
Exemption
Expedited
Full
(Must be risk level 1)
 
IMPORTANT NOTE: You will not be able to change your selections for "Which IRB" and "Protocol Process Type" after
saving this section. If you select the wrong IRB or Protocol Process Type, you may need to create a new application. 
See below for guidance on these options, or refer to ORI's "Getting Started" page. Please contact the Office of Research Integrity
(ORI) at 859-257-9428 with any questions prior to saving your selections.
 
*Which IRB*
The Medical IRB reviews research from the Colleges of:
Dentistry
Health Sciences
Medicine
Nursing
Pharmacy and Health Sciences
and Public Health.
 
The Nonmedical IRB reviews research from the Colleges of:
Agriculture
Arts and Sciences
Business and Economics
Communication and Information
Design; Education
Fine Arts
Law
and Social Work
Note: Studies that involve administration of drugs, testing safety or effectiveness of medical devices, or invasive medical procedures
must be reviewed by the Medical IRB regardless of the college from which the application originates. 
*Which Protocol Process Type* 
Under federal regulations, the IRB can process an application to conduct research involving human subjects in one of three ways: 
by exemption certification
by expedited review.
by full review;
The investigator makes the preliminary determination of the type of review for which a study is eligible. Please refer to ORI's "Getting
Started" page for more information about which activities are eligible for each type of review.
 
The revised Common Rule expanded exemption certification category 4 for certain secondary research with
identifiable information or biospecimens. The regulations no longer require the information or biospecimens to be
existing.  For more information see the Exemption Categories Tool.
Section 1 Page 1 of 2
IRB Approval
2/14/2023
IRB # 59128
IRB3

PROJECT INFORMATION
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Title of Project: (Use the exact title listed in the grant/contract application, if applicable). 
If your research investigates any aspect of COVID-19, please include "COVID19" at the beginning of your Project Title and Short Title 
MCC-20-MULTI-37: A Pilot Feasibility Study of generation
sequencing-based stratification of front line treatment of
high grade neuroendocrine carcinoma(Precision-Nec)
Short Title Description 
Please use a few key words to easily identify your study - this text will be displayed in the Dashboard listing for your study.
20-MULTI-37
Anticipated Ending Date of Research Project: 
Maximum number of human subjects (or records/specimens to be reviewed) 
15
After approval, will the study be open to enrollment of new subjects or new data/specimen collection? 
Yes
No
5/31/2032
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RISK LEVEL
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Indicate which of the categories listed below accurately describes this protocol
(Risk Level 1) Not greater than minimal risk
(Risk Level 2) Greater than minimal risk, but presenting the prospect of direct benefit to individual subjects
(Risk Level 3) Greater than minimal risk, no prospect of direct benefit to individual subjects, but likely to yield generalizable
knowledge about the subject's disorder or condition.
(Risk Level 4) Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious
problem affecting the health or welfare of subjects.
*“Minimal risk” means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of
themselves from those ordinarily encountered in daily life or during the performance of routine physical or psychological
examination or tests.
Refer to UK's guidance document on assessing the research risk for additional information.
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SUBJECT DEMOGRAPHICS
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Age level of human subjects: (i.e., 6 mths.; 2yrs., etc..) 18 yrs to 99 yrs
Study Population:
Describe the characteristics of the subject population, including age range, gender, ethnic background and health status. Identify the criteria for inclusion and
exclusion. 
Provide the following information:
A description of the subject selection criteria and rationale for selection in terms of the scientific objectives and proposed study design;
A compelling rationale for proposed exclusion of any sex/gender or racial/ethnic group;
Justification for the inclusion of vulnerable groups such as children, prisoners, adults with impaired consent capacity, or others who may be vulnerable to
coercion or undue influence.
Please consider these resources: 
NIH Diversity Policy 
FDA Diversity Guidance 
Adult patients with histopathologically confirmed metastatic high-grade neuroendocrine carcinoma (excluding small cell carcinoma) of all types managed at the
MCC will be considered potential candidates for this clinical trial. Specific criteria is listed below.
3.1.1 Histopathologically confirmed high-grade neuroendocrine carcinoma (i.e., large cell carcinoma, poorly differentiated neuroendocrine carcinoma, or mixed
high grade neuroendocrine neoplasm) that is metastatic and/or not resectable.
3.1.2 Adequate tissue is available for genomic sequencing. Prior CLIA certified NGS report, if available, will also be acceptable for review by MCC’s MTB.
3.1.3 Age 18 years or older
3.1.4 ECOG performance status = 2 (Appendix A)
3.1.5 Ability to understand and the willingness to sign a written informed consent document.
3.1.6 Patients may have received up to two cycles of chemotherapy prior to enrollment if deemed as an urgent clinical necessity or under visceral crisis; as
determined by the treating physician, because these circumstances preclude the delay in treatment required for molecular profiling.
3.1.7 Adequate Bone Marrow Function 
Absolute neutrophil count (ANC) = 1.5 × 109/L, Platelets = 100 × 109/L, Hemoglobin = 8 g/dL independent of transfusion = 14 days prior to screening.
3.1.8 Adequate Hepatic Function
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × upper limit of normal (ULN); if liver metastases, then = 5 × ULN
Bilirubin = 1.5 × ULN; = 2 × ULN if hyperbilirubinemia is due to Gilbert’s syndrome
3.1.9 Adequate Renal Function
Measured or calculated creatinine clearance (CrCL) = 60 mL/min. For calculated CrCL, the Cockcroft Gault formula or institutional standard formula can be
used.
Exclusion Criteria
3.2.1 Patients with small cell carcinoma are excluded from the study
3.2.2 Patients with psychiatric illness or social situations that would limit compliance with study requirements.
3.2.3 Pregnant and nursing women, because of teratogenicity and toxicity risks.
3.2.4 Patients who have completed more than two cycles of chemotherapy for the current cancer diagnosis.
3.2.5 Patients with resectable cancer or eligible for curative therapy.
3.2.6 Patients with an actionable mutation for which Markey MTB or NCCN guidelines recommend up-front therapy with targeted agents (e.g., EGFR mutation,
Alk Fusion, ROS1 mutation, etc.).
Attachments
Indicate the targeted/planned enrollment of the following members of minority groups and their subpopulations. Possible demographic
sources: Census Regional Analyst Edition, Kentucky Race/Ethnic Table, Kentucky Population Data. 
(Please note: The IRB will expect this information to be reported at Continuation Review time for Pre-2019 FDA-regulated
Expedited review and Full review applications):
Participant Demographics
Cisgender Man 
Cisgender Woman 
TGNB/TGE 
Unknown/Not Reported
American
Indian/Alaskan
Native:
Asian:
Black/African
American:
Latinx:
Native
Hawaiian/Pacific
Islander:
White:
American
Arab/Middle
Eastern/North
African:
1
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Indigenous
People Around
the World:
More than One
Race:
Unknown or Not
Reported:
 
If unknown, please explain why:
Indicate the categories of subjects and controls to be included in the study. You may be required to complete additional forms depending on
the subject categories which apply to your research. If the study does not involve direct intervention or direct interaction with subjects, (e.g.,
record-review research, outcomes registries), do not check populations which the research does not specifically target. For example: a large
record review of a diverse population may incidentally include a prisoner or an international citizen, but you should not check those categories
if the focus of the study has nothing to do with that status.
Check All That Apply (at least one item must be selected)
Children (individuals under age
18)
Wards of the State (Children)
Emancipated Minors
Students
College of Medicine Students
UK Medical Center Residents or
House Officers
Impaired Consent Capacity
Adults
Pregnant Women/Neonates/Fetal
Material
Prisoners
Non-English Speaking (translated
long or short form)
International Citizens
Normal Volunteers
Military Personnel and/or DoD
Civilian Employees
Patients
Appalachian Population
ADDITIONAL INFORMATION:
Please visit the IRB Survival Handbook for
more information on:
Children/Emancipated Minors
Students as Subjects
Prisoners
Impaired Consent Capacity Adults
Economically or Educationally
Disadvantaged Persons
Other Resources:
UKMC Residents or House Officers
[see requirement of GME]
Non-English Speaking [see also the
E-IRB Research Description section
on this same topic]
International Citizens [DoD SOP may
apply]
Military Personnel and/or DoD Civilian
Employees
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Traumatic brain injury or acquired brain
injury
Severe depressive disorders or Bipolar
disorders
Schizophrenia or other mental disorders
that
involve serious cognitive disturbances
Stroke
Developmental disabilities
Degenerative dementias
CNS cancers and other cancers with
possible CNS involvement
Late stage Parkinson’s Disease
Late stage persistent substance
dependence
Ischemic heart disease
HIV/AIDS
COPD
Renal insufficiency
Diabetes
Autoimmune or inflammatory disorders
Chronic non-malignant pain disorders
Drug effects
Other acute medical crises
Assessment of the potential recruitment of subjects with impaired consent capacity (or likelihood):
Check this box if your study does NOT involve direct intervention or direct interaction with subjects (e.g., record-review research, secondary
data analysis). If there is no direct intervention/interaction you will not need to answer the impaired consent capacity questions.
Does this study focus on adult subjects with any conditions that present a high likelihood of impaired consent capacity or fluctuations in
consent capacity? (see examples below)
Yes
No
If Yes and you are not filing for exemption certification, go to "Form T", complete the form, and attach it using the button below.
Examples of such conditions include:
Attachments
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INFORMED CONSENT/ASSENT PROCESS/WAIVER
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For creating your informed consent attachment(s), please download the most up-to-date version listed in "All Templates" under the
APPLICATION LINKS menu on the left, and edit to match your research project.
Additional Resources:
Informed Consent/Assent Website
Waiver of Consent vs. Waiver of Signatures
Sample Repository/Registry/Bank Consent Template
Consent/Assent Tips:
If you have multiple consent documents, be sure to upload each individually (not all in a combined file).
If another site is serving as the IRB for the project, attach the form as a “Reliance Consent Form” so the document will not receive
a UK IRB approval stamp; the reviewing IRB will need to stamp the consent forms.
Changes to consent documents (e.g., informed consent form, assent form, cover letter, etc...) should be reflected in a 'tracked
changes' version and uploaded separately with the Document Type "Highlighted Changes".
It is very important that only the documents you wish to have approved by the IRB are attached; DELETE OUTDATED FILES --
previously approved versions will still be available in Protocol History.
Attachments that are assigned a Document Type to which an IRB approval stamp applies will be considered the version(s) to be
used for enrolling subjects once IRB approval has been issued. 
Document Types that do NOT get an IRB approval stamp are:
"Highlighted Changes",
"Phone Script", and
"Reliance Consent Form",
"Sponsor's Sample Consent Form".
How to Get the Section Check Mark
1. You must:
a) provide a response in the text box below describing how investigators will obtain consent/assent, and 
b) check the box for at least one of the consent items and/or check mark one of the waivers
2. If applicable attach each corresponding document(s) as a PDF.
3. If you no longer need a consent document approved (e.g., closed to enrollment), or, the consent document submitted does not
need a stamp for enrolling subjects (e.g., umbrella study, or sub-study), only select "Stamped Consent Doc(s) Not Needed".
4. After making your selection(s) be sure to scroll to the bottom of this section and SAVE your work!
Check All That Apply
Informed Consent Form (and/or Parental Permission Form and/or translated short form)
Assent Form
Cover Letter (for survey/questionnaire research)
Phone Script
Informed Consent/HIPAA Combined Form
Debriefing and/or Permission to Use Data Form
Reliance Consent Form
Sponsor's sample consent form for Dept. of Health and Human Services (DHHS)-approved protocol
Stamped Consent Doc(s) Not Needed
Attachments
Attach Type
File Name
Informed Consent/HIPAA Combined Form
MULTI-37 Consent-HIPAA vd 2-13-2023 CELAN PI CHANGE.pdf
InformedConsent-Highlighted/Tracked_Changes MULTI-37 Consent-HIPAA vd 2-13-2023 TRACKED PI Change.pdf
Informed Consent Process:
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Using active voice, describe how investigators will obtain consent/assent. Include:
the circumstances under which consent will be sought and obtained
the timing of the consent process (including any waiting period between providing information and obtaining consent)
who will seek consent
how you will minimize the possibility of coercion or undue influence
the method used for documenting consent
if applicable, who is authorized to provide permission or consent on behalf of the subject
if applicable, specific instruments or techniques to assess and confirm potential subjects’ understanding of the information
Note: all individuals authorized to obtain informed consent should be designated as such in the E-IRB "Study Personnel" section of
this application.
Special considerations may include:
Obtaining consent/assent for special populations such as children, prisoners, or people with impaired decisional capacity
Research Involving Emancipated Individuals 
If you plan to enroll some or all prospective subjects as emancipated, consult with UK legal counsel prior to submitting this
application to the IRB. Include research legal counsel’s recommendations in the "Additional Information" section as a separate
document.
Research Involving Non-English Speaking Subjects 
For information on inclusion of non-English speaking subjects, or subjects from a foreign culture, see IRB Application Instructions
for Recruiting Non-English Speaking Participants or Participants from a Foreign Culture.
Research Repositories 
If the purpose of this submission is to establish a research repository describe the informed consent process. For guidance
regarding consent issues, process approaches, and sample language see the Sample Repository/Registry/Bank Consent
Template.
Once a subject is referred for consideration in the study, the subject’s history and status will be completely evaluated and treatment
recommendations will then be discussed thoroughly with the subject. Any alternative forms of therapy will be presented as objectively
as possible. The risks and hazards of the study drugs recommended will be explained to the subject. The Investigator shall seek
consent only under circumstances that provide the subject sufficient opportunity to consider whether or not to participate and that
minimize the possibility of coercion or undue influence. The subject will be given as much time as needed to review the consent and
ask any questions before making a decision. The subject will then receive a signed copy of the consent form.
Requests for information about the research or complaints will be addressed to the PI, research staff, Ombudsman or Office of
Research Integrity as appropriate. All requests or complaints will be handled in a timely, courteous, and confidential manner following
University policies.
Request for Waiver of Informed Consent Process
If you are requesting IRB approval to waive the requirement for the informed consent process, or to alter some or all of the
elements of informed consent, complete, Section 1 and Section 2 below.
Note: The IRB does not approve waiver or alteration of the consent process for greater than minimal risk research, except
for planned emergency/acute care research as provided under FDA regulations. Contact ORI for regulations that apply to
single emergency use waiver or acute care research waiver (859-257-9428).
SECTION 1.
Check the appropriate item:
I am requesting a waiver of the requirement for the informed consent process.
I am requesting an alteration of the informed consent process.
If you checked the box for this item, describe which elements of consent will be altered and/or omitted, and justify the
alteration.
SECTION 2.
Explain how each condition applies to your research.
a) The research involves no more than minimal risk to the subject.
b) The rights and welfare of subjects will not be adversely affected.
c) The research could not practicably be carried out without the requested waiver or alteration.
d) Whenever possible, the subjects or legally authorized representatives will be provided with additional pertinent information
after they have participated in the study.
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e) If the research involves using or accessing identifiable private information or identifiable biospecimens, the research could
not practicably be carried out without using such information or biospecimens in an identifiable format.
Private information/specimens are “identifiable” if the investigator may ascertain the identity of the subject or if identifiers
are associated with the information (e.g., medical records). This could be any of the 18 HIPAA identifiers including dates
of service.
If not using identifiable private information or identifiable biospecimens, insert N/A below.
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Request for Waiver of Signatures
If you are requesting IRB approval to waive the requirement for signatures on informed consent forms, your research
activities must fit into one of three regulatory options:
1. The only record linking the participant and the research would be the consent document, and the principal risk would be
potential harm resulting from a breach of confidentiality (e.g., a study that involves participants who use illegal drugs).
2. The research presents no more than minimal risk to the participant and involves no procedures for which written consent
is normally required outside of the research context (e.g., a cover letter on a survey, or a phone script).
3. The participant (or legally authorized representative) is a member of a distinct cultural group or community in which
signing forms is not the norm, the research presents no more than minimal risk to the subject, and there is an appropriate
alternative mechanism for documenting that informed consent was obtained.
Select the option below that best fits your study. 
If the IRB approves a waiver of signatures, participants must still be provided oral or written information about the study.
To ensure you include required elements in your consent document, use the Cover Letter Template as a guide. There is
an English and a Spanish version.
 
Option 1
Describe how your study meets these criteria:
a) The only record linking the participant and the research would be the consent document:
b) The principal risk would be potential harm resulting from a breach of confidentiality (i.e., a study that involves subjects
who use illegal drugs).
Under this option, each participant (or legally authorized representative) must be asked whether (s)he wants to sign a
consent document; if the participant agrees to sign a consent document, only an IRB approved version should be
used.
Option 2
Describe how your study meets these criteria:
a) The research presents no more than minimal risk to the participant:
b) Involves no procedures for which written consent is normally required outside of the research context (i.e. a cover
letter on a survey, or a phone script):
Option 3
Describe how your study meets these criteria:
a) The subject (or legally authorized representative) is a member of a distinct cultural group or community in which
signing forms is not the norm.
b) The research presents no more than minimal risk to the subject.
c) There is an appropriate alternative mechanism for documenting that informed consent was obtained.
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RESEARCH DESCRIPTION
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You may attach a sponsor’s protocol pages in the “Additional Information” section and refer to them where necessary in
the Research Description. However, each prompt that applies to your study should contain at least a summary paragraph.
Pro Tips:
Save your work often to avoid losing data.
Use one of the attachment buttons in this section or under the Additional Information section to include supplemental
information with your application. During the document upload process, you will be able to provide a brief description
of the attachment.
Background
Include a brief review of existing literature in the area of your research. You should identify gaps in knowledge that should be addressed
and explain how your research will address those gaps or contribute to existing knowledge in this area. For interventional research,
search PubMed and ClinicalTrials.gov for duplicative ongoing and completed trials with same condition and intervention(s).
Neuroendocrine tumors vary widely in both disease site and grade, ranging from low grade, relatively benign carcinoid tumors to
aggressive and rapidly fatal high-grade neuroendocrine carcinomas. High grade neuroendocrine carcinomas (HG-NECs) can originate
anywhere in the body, and are highly aggressive, with dismal 5-year overall survival rates. The lung and gastrointestinal tract (small
bowel, colon, rectum or pancreas) form the majority of these HG-NECs sites. HG-NECs are classified into three subtypes based on
histopathology, specifically, as small cell neuroendocrine carcinoma, large cell neuroendocrine carcinoma (LCNEC) or poorly
differentiated neuroendocrine carcinoma. 
There is a lack of consensus for upfront systemic regimens for HG-NECs and as such, treatment is often per physician preference.
Most often, HG-NECs are treated with platinum-based chemotherapeutic regimens, with marked heterogeneity in response. It is well
established that small cell neuroendocrine carcinomas are characterized by a co-mutation for TP53 and RB1, and are exceptionally
platinum-sensitive. However less is known about LCNECs. 
Large-Cell Neuroendocrine Carcinoma
LCNEC was first introduced in 1991 by Travis et. al [5] as a new type of lung cancer. The 2015 World Health Organization
Classification categorized LCNEC under neuroendocrine tumors, along with typical carcinoma, atypical carcinoma and the more
undifferentiated tumor represented by small cell lung cancer. Prior to 2015, LCNEC was classified under a general category of large
cell carcinoma, however as pathologists studied this entity in detail, it was evident that LCNEC has a distinct clinicopathological identity
[6-8]. Histopathologically, these tumors are characterized by high mitotic rate (more than 10 mitosis per high power field), extensive
necrosis, and neuroendocrine features, specifically the presence of chromogranin A, neuron specific enolase and synaptophysin.
LCNEC is a rare and aggressive disease with a paucity of data regarding disease progression. Precise incidence and prevalence is
unknown. From 2003-2012, the Dutch Cancer Registry reported 952 histologically confirmed new cases of pulmonary LCNECs.
Among these cases, 383 patients presented with advanced disease, primarily metastases to liver, bone or brain. The prognosis is
poor with overall 5-year survival for metastatic disease less than 5% , which is similar to small cell lung cancer (SCLC), although some
studies suggest that the prognosis for early stage LCNEC might be slightly better and similar to non-small cell lung cancer (NSCLC). 
Molecular Profiling of HG-NECs
Molecular profiling of small-cell neuroendocrine carcinomas is well established and validated, indicating universally expressed co-
mutation for TP53 and RB1 [2]. Recently there have been attempts to define genomic profiles of LCNEC. The development of a 241-
gene panel on pulmonary tumors, next generation sequencing allows LCNECs to be further defined. 
Based on specific genetic signatures, Rekhtman and colleagues sub-classified 45 LCNECs into two major cohorts: 
small cell-like (TP53/RB1 co-mutated; n=18) and 
non-small cell-like (n=25), 
as well as one minor cohort (carcinoid-like n=2). 
Similarly, molecular profiling of gastrointestinal high-grade neuroendocrine carcinomas (GI-NECs) indicate that they can also be
dichotomously categorized by the presence or absence of co-mutations for TP53 and RB1. 
Treatment regimens for small cell neuroendocrine carcinoma are well established, based on clinical trials conducted in SCLC. In
contrast, current guidelines regarding optimal treatment for large-cell and poorly differentiated neuroendocrine carcinomas are
nonexistent, driven by the paucity of data on these rare and highly fatal tumors. Additionally, the WHO recently defined a new subtype
of high-grade neuroendocrine carcinoma, mixed neuroendocrine neoplasm (MINEN), which features characteristics found in large-cell
carcinomas and in other tumor types, including adenocarcinomas for example. 
To date, there are no prospective randomized clinical trials examining front line therapies for metastatic HG-NECs, based on mutational
profiles. Given the gap in evidence-based information for treatment and the emerging more refined classification of these tumors, we
propose to utilize recent genomic profiles of high-grade large cell neuroendocrine carcinomas to guide and inform clinicians of optimal
treatments. 
We hypothesize that upfront genetic profiling of HG-NEC can segregate these tumors into NGS-based groups that will impact
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treatment decisions (feasibility study) and ultimately, improve overall treatment response and outcomes.
Objectives
List your research objectives. Please include a summary of intended research objectives in the box below.
Primary Objective 
To study the feasibility of upfront next generation sequencing (NGS) directed treatment in high grade neuroendocrine carcinomas
(excluding small cell carcinoma). Feasibility is defined as being able to sequence the patient within 2 months of initial medical oncology
visit and more than 50% of patients are assigned to molecularly defined cohorts (TP53 and RB1 co-mutated vs. non-co-mutated).
Secondary Objectives:
To evaluate progression-free survival on front-line chemotherapy.
To evaluate the objective response rate.
Exploratory Objective: To identify prevalence of potentially targetable mutations in high grade neuroendocrine carcinoma
Study Design
Describe and explain the study design (e.g., observational, secondary analysis, single/double blind, parallel, crossover, deception, etc.).
Clinical Research: Indicate whether subjects will be randomized and whether subjects will receive any placebo.
Community-Based Participatory Research: If you are conducting community-based participatory research (CBPR), describe
strategies for involvement of community members in the design and implementation of the study, and dissemination of results from
the study.
Qualitative research: Indicate ranges where flexibility is needed, if a fixed interview transcript is not available, describe interview
topics including the most sensitive potential questions.
Research Repositories: If the purpose of this submission is to establish a Research Repository (bank, registry) and the material
you plan to collect is already available from a commercial supplier, clinical lab, or established IRB approved research repository,
provide scientific justification for establishing an additional repository collecting duplicate material. Describe the repository design
and operating procedures. For relevant information to include, see the UK Research Biospecimen Bank Guidance or the UK
Research Registry Guidance.
This is a single-arm, pilot trial in patients with metastatic high grade large cell neuroendocrine carcinoma (HG-LCNEC) to study the
feasibility of upfront NGS directed treatment in high grade neuroendocrine carcinomas. Tumor samples will receive next generation
sequencing (NGS) profiling to classify the tumor as one of three subtypes: small cell-like, non-small cell-like or non-typeable. Non-
typeable cases will not be eligible for participation in this study, neither is small cell neuroendocrine carcinoma (HG-SCNEC). The
systemic therapy regimen will be determined based on the NGS profile of the tumor. 
Feasibility is defined as being able to sequence the patient within 2 months of initial medical oncology visit and being able to assign
into molecularly-defined cohorts (TP53 and RB1 co-mutated vs non-co-mutated). 
Secondary outcomes include ORR and progression-free survival (PFS). Radiological response will be assessed via RECIST Version
1.1 criteria (Appendix B) based on standard-of-care CT scans completed at q2 monthly intervals during treatment and q3 month during
observation. PFS is defined from date of on study to the date of disease progression or death or date of last follow-up whichever
occurs first. PFS will be assessed via standard-of-care CT scans (q2 month intervals during active treatment and q3 months during
observation) as graded by RECIST Version 1.1 criteria for up to three years post-study enrollment.
All patients who received anticancer therapy will be included in the toxicity and safety analysis. Incidence tables will be generated to
summarize incidence of patients reporting at least one episode of each specific AE, the incidence of AE causing withdrawal from the
study and incidence of SAE. The total number of episodes for each event reported (Frequency Table), the severity and attribution to
study therapy of each episode reported (Severity Table and Attribution Table) will also be evaluated.
Subjects receive treatment on the recommended regimens for as long as the treating oncologist feels they are benefiting from the
treatment, and the patient wishes to continue. Subjects will be followed until disease progression.
Attachments
Attach Type
File Name
StudyDesign
Attachment_Treatment plan schema.pdf
Subject Recruitment Methods & Advertising
Describe how the study team will identify and recruit subjects. Please consider the following items and provide additional information as
needed so that the IRB can follow each step of the recruitment process.
How will the study team identify potential participants?
Who will first contact the potential subjects, and how?
Will you use advertisements? If so, how will you distribute those?
How and where will the research team meet with potential participants?
If applicable, describe proposed outreach programs for recruiting women, minorities, or disparate populations.
How you will minimize undue influence in recruitment?
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Attach copies of all recruiting and advertising materials (emails, verbal scripts, flyers, posts, messages, etc.).
For additional information on recruiting and advertising:
IRB Application Instructions - Advertisements
PI Guide to Identification and Recruitment of Human Subjects for Research
Subjects will be identified by referral from community oncologist and primary care physicians, as well as internal referrals from
physicians at the University of Kentucky’s multidisciplinary cancer program. Subjects will initially be evaluated by treating oncologist,
and will be offered initial information about the clinical trial if appropriate. Agreeable subjects will then be invited to participate in an
informed consent process as described below. The study will be posted on the web-site of the Markey Cancer Center in the general
information list and listed in the Markey Cancer Center quarterly: Clinical Research Newsletter. The study is also currently posted at
ClinicalTrials.gov.
We do not plan to do any advertisments.
Attachments
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Research Procedures
Describe how the research will be conducted.
What experience will study participants have?
What will study participants be expected to do?
How long will the study last?
Outline the schedule and timing of study procedures.
Provide visit-by-visit listing of all procedures that will take place.
Identify all procedures that will be carried out with each group of participants.
Describe deception and debrief procedures if deception is involved.
Differentiate between procedures that involve standard/routine clinical care and those that will be performed specifically for this
research project. List medications that are explicitly forbidden or permitted during study participation.
Prior to any study-required tests, subjects must provide written informed consent to participate in this study. It is now standard of care
to send tumor tissue for molecular testing so subjects may begin standard of care (SOC) treatment while waiting for results from this
test. Patients can receive up to two cycles of Standard of Care (SOC) chemotherapy while NGS results are being obtained before the
patient can be presented at Markey Molecular Tumor Board (MTB). Based on the results, subjects may then be changed to a different,
FDA-approved treatment which matches the molecular patterns. All study visits, labs, tests and procedures are SOC and would be
done if the subject were not on study. 
Screening shall include: complete history; physical examination and evaluation of ECOG (Eastern Cooperative Oncology Group)
Performance Status; histopathological confirmed diagnosis of high grade neuroendocrine carcinoma; CBC; serum chemistries and
baseline computerized tomographic (CT) scan (within 6 weeks of starting treatment) for RECIST 1.1 evaluation. Baseline lab tests and
radio-graphic studies should be completed within 6 weeks prior to registration/initiation of treatment. All of these are standard of care
for metastatic carcinoma of HG-NEC type. 
The case will be reviewed at MTB once the NGS report is ready, patient meets inclusion criteria and has consented to participate in the
study. The MTB will provide a written review of the molecular sequencing of the subject, and the study statistician will review and assign
subjects to cohorts, in consultation with the PI. Subjects will be assigned to the current FDA-approved, NCCN-recommended
treatment regimen based on their molecular profile and will continue treatment for as long as the risk-benefit profile remains favorable,
the study remains active, and they wish to continue. 
All the procedures to be carried out are illustrated in the attached study calendar. All the tests/procedures are standard of care for this
patient population.
Attachments
Attach Type
File Name
ResearchProcedures
Study Calander.pdf
Data Collection & Research Materials
In this section, please provide the following:
Describe all sources or methods for obtaining research materials about or from living individuals (such as specimens, records,
surveys, interviews, participant observation, etc.), and explain why this information is needed to conduct the study.
For each source or method described, please list or attach all data to be collected (such as genetic information, interview scripts,
survey tools, data collection forms for existing data, etc.).
If you will conduct a record or chart review, list the beginning and end dates of the records you will view.
This study has no data collection instruments.
Attachments
Resources
Describe the availability of the resources and adequacy of the facilities that you will use to perform the research. Such resources may
include:
Staffing and personnel, in terms of availability, number, expertise, and experience;
Computer or other technological resources, mobile or otherwise, required or created during the conduct of the research;
Psychological, social, or medical services, including equipment needed to protect subjects, medical monitoring, ancillary care, or
counseling or social support services that may be required because of research participation;
Resources for communication with subjects, such as language translation/interpretation services.
Research staff of the Markey Cancer Center Clinical Research Organization with oncology research related experience, ranging from
one to fifteen years, will assist the PI in the conduct of the study. All subjects will have study medication dispensed in the Markey
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Cancer Center’s closely monitored clinic area, with on-site pharmacy and medical support, certified oncology nurses and ready access
to emergency care. The University’s social 
Additional Key Personnel for this study are identified on the MCC-CRO Global KP (MCCCRO Master SP List). This allows for cross-
coverage of studies managed by the MCC-CRO.
Potential Risks & Benefits
Risks
Describe any potential risks – including physical, psychological, social, legal, ability to re-identify subjects, or other risks. Assess
the seriousness and likelihood of each risk.
Which risks may affect a subject’s willingness to participate in the study?
Describe likely adverse effects of drugs, biologics, devices or procedures participants may encounter while in the study.
Qualitative research - describe ethical issues that could arise while conducting research in the field and strategies you may use to
handle those situations.
Describe any steps to mitigate these risks.
Benefits
Describe potential direct benefits to study participants – including diagnostic or therapeutic, physical, psychological or emotional,
learning benefits. This cannot include incentives or payments.
State if there are no direct benefits.
Describe potential benefits to society and/or general knowledge to be gained.
Describe why potential benefits are reasonable in relation to potential risks. If applicable, justify why risks to vulnerable subjects are
reasonable to potential benefits.
Tumor tissue collected will be left-over from SOC biopsies. Risks of blood draw include soreness, bruising, pain, infection, possible
fainting, bleeding. 
Risks of having genetic testing for this study relate to accidental breach of confidence and would include emotional, social, or financial
consequences. In some cases, it could be used to make it harder for the subject to get or keep a job or health insurance. Genetic
information could be used in ways that could cause the subject or their family distress. We will take every precaution to protect our
subjects' information.
HG-NEC is an aggressive cancer with poor prognosis. At the time of this study, overall 5-year survival for metastatic disease is less
than 5 percent. Currently, there is no standard front-line treatment. Physician mainly treat with platinum based chemotherapy with
markedly uneven results. The treatment plan matched specifically to the subjects' molecular profile should be more effective than the
usual treatment approach. As all therapies recommended will be the current FDA-approved treatments for that molecular pattern, we
feel the risk-benefit ratio is acceptable.
Available Alternative Opportunities/Treatments
Describe alternative treatments or opportunities that might be available to those who choose not to participate in the study, and which
offer the subject equal or greater advantages. If applicable, this should include a discussion of the current standard of care treatment(s).
Subjects can get the usual treatment for this type of cancer without being on study. They can participate in another study, if one is
available. They can receive only palliative care or refuse all treatment.
Back to Top
Records, Privacy, and Confidentiality
Specify where the data and/or specimens will be stored and how the researcher will ensure the privacy and confidentiality of both.
Specify who will have access to the data/specimens and why they need access.
Describe how data will be managed after the study is complete:
If data/specimens will be maintained, specify whether identifiers will be removed from the maintained information/material.
If identifiers will not be removed, provide justification for retaining them and describe how you will protect confidentiality.
If the data/specimens will be destroyed, verify that this will not violate retention policies and will adhere to applicable facility
requirements.
If this study will use de-identified data from another source, describe what measures will be taken to ensure that subject identifiers are
not given to the investigator.
If applicable, describe procedures for sharing data/specimens with collaborators not affiliated with UK.
For additional considerations: 
Return of Research Results or Incidental Research Findings 
HIPAA policies 
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FERPA policies 
Procedures for Transfer agreements 
Information regarding multi-site studies 
NIH Genomic Data Sharing (GDS) Policy 
Digital Data
Specimens from subjects (either archival or fresh tumor tissue) are reviewed for NGS status for participation in the study.
Medical/Clinical information pertaining to the protocol is included in the subjects’ medical records. Copies are also kept in subjects’
protocol charts. This ensures timely record review, and allows for collection of data points required to meet primary and secondary
objectives of the study.
Confidentiality of medical information is discussed at length in the informed consent. Subjects are made aware of what data will be
collected, where it is stored and who has access to the information. Study data may be published or shared with other researchers, but
the identity and medical history of each study participant will remain strictly confidential. Representatives of University of Kentucky,
Markey Cancer Center, the Food and Drug Administration (FDA), the Kentucky Cancer Registry, and the Institutional Review Board
(IRB) may review the study data and medical records relating to this research study. 
During the study, information will be collected to assess compliance with the study requirements. These records will be used by the
Markey Cancer Center in connection with complying with their obligations relating to this study. The records will not be used for any
other purposes or disclosed to any other party without the subject’s permission. All records will be coded with an identification number
to protect their identity. Data will be stored in a secured area for at least six years or two years after the study is completed, whichever
occurs first. All data stored is on site at Markey Cancer Center Clinical Research Organization in locked facilities, and with limited
access to records by designated research staff. All research records will be held for a minimum of six years following completion of
the study.
Patients enrolled in this study will be evaluated clinically and with standard laboratory tests before and at regular intervals during their
participation in this study. Safety will be assessed by physical examinations, ECGs, clinical chemistry and hematology tests and
monitoring of adverse events. Adverse events that occur between the signing of the informed consent through 30 days following the
last dose of study drug will be recorded. The severity of adverse events will be assessed using National Cancer Institute Common
Terminology Criteria for Adverse Events, Version 5.
UK IRB policies state that IRB-related research records must be retained for a minimum of 6 years after study closure. Do
you confirm that you will retain all IRB-related records for a minimum of 6 years after study closure?
Yes
No
Payment
Describe the incentives (monetary or other) being offered to subjects for their participation. If monetary compensation is offered,
indicate the amount and describe the terms and schedule of payment. Please review this guidance for more information on payments to
subjects, including restrictions and expectations.
Subjects will not receive any payment for participating in this study.
Costs to Subjects
Include a list of services and/or tests that will not be paid for by the sponsor and/or the study (e.g., MRI, HIV). Keep in mind that a
subject will not know what is “standard” – and thus not covered by the sponsor/study – unless you tell them.
All tests, visits, and procedures are standard of care for this patient population and will be billed to the subject's insurance. All drugs
recommended will be FDA-approved for the tumor markers and the drugs will be charged to the subject's insurance.
Data and Safety Monitoring
The IRB requires review and approval of data and safety monitoring plans for greater than minimal risk research or NIH-funded/FDA-
regulated clinical investigations.
If you are conducting greater than minimal risk research, or your clinical investigation is NIH-funded, describe your Data and Safety
Monitoring Plan (DSMP). Click here for additional guidance on developing a Data and Safety Monitoring Plan.
If this is a non-sponsored investigator-initiated protocol considered greater than minimal risk research, and if you are planning on
using a Data and Safety Monitoring Board (DSMB) as part of your DSMP, click here for additional guidance for information to
include with your IRB application.
The Principal Investigator has primary responsibility for monitoring the safe conduct of this study. Additionally, the Markey Cancer
Center Data Safety and Monitoring Committee outlines oversight and monitoring of all cancer clinical trials. The Committee is
responsible for reviewing data to identify patient safety and protocol compliance issues. The Markey Protocol Review Committee
(PRC) assigns studies a DSMC review timeline based on the phase, origination of the study and known safety issues.
The members of the MCC DSMC consist of Medical Oncologists, a Pharmacist, a Nurse Manager, a Certified Clinical Research
Professional and a Reporter. These members were selected based on their experience, reputation for objectivity, and knowledge of
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clinical trial methodology. The DSMC reviews the protocol to assure the following: progress of the trial and safety of participants;
compliance with requirements for the reporting of adverse events; any actions resulting in a temporary or permanent suspension by the
sponsor; and data accuracy and protocol compliance. The DSMC, the Protocol Review Committee (PRC), the responsible disease-
specific Clinical Care and Research Team (CCART) and/or the UK IRB are empowered to immediately suspend accrual to any study
under its purview for failure to comply with AE/SAE reporting requirements, poor study enrollment, protocol violations or issues related
to patient safety.
Back to Top
Future Use and Sharing of Research Data
If the results of this study will be used by members of the research team or shared with other researchers for future studies, please
address the following:
list the biological specimens and/or information that will be kept
briefly describe the types, categories and/or purposes of the future research
describe any risks of the additional use
describe privacy/confidentiality protections that will be put into place
describe the period of time specimens/information may be used
describe procedures for sharing specimens/information with secondary researchers
describe the process for, and limitations to, withdrawal of specimens/data
Your information or samples collected for this study will NOT be used or shared for future research studies, even if we remove the
identifiable information like your name, medical record number, and/or date of birth.
Are you recruiting or expect to enroll Non-English Speaking Subjects or Subjects from a Foreign Culture? (does not include short
form use for incidentally encountered non-English subjects)
Yes
No
Non-English Speaking Subjects or Subjects from a Foreign Culture
Recruitment and Consent:
Describe how information about the study will be communicated to potential subjects appropriate for their culture, and if necessary,
how new information about the research may be relayed to subjects during the study. 
When recruiting Non-English-speaking subjects, provide a consent document in the subject’s primary language. After saving this
section, attach both the English and translated consent documents in the “Informed Consent" section. 
Cultural and Language Consultants:
The PI is required to identify someone who is willing to serve as the cultural consultant to the IRB.
This person should be familiar with the culture of the subject population and/or be able to verify that translated documents are
the equivalent of the English version of documents submitted.
The consultant should not be involved with the study or have any interest in its IRB approval.
Please include the name, address, telephone number, and email of the person who agrees to be the cultural consultant for
your study.
ORI staff will facilitate the review process with your consultant. Please do not ask them to review your protocol separately.
For more details, see the IRB Application Instructions on Research Involving Non-English Speaking Subjects or Subjects from a
Foreign Culture. 
Local Requirements:
If you will conduct research at an international location, identify and describe:
relevant local regulations
data privacy regulations
applicable laws
ethics review requirements for human subject protection
Please provide links or sources where possible. If the project has been or will be reviewed by a local ethics review board, attach a
copy in the “Additional Information/Materials” section. You may also consult the current edition of the International Compilation of
Human Research Standards
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Does your study involve HIV/AIDS research and/or screening for other reportable diseases (e.g., Hepatitis C, etc…)?
Yes
No
HIV/AIDS Research
If you have questions about what constitutes a reportable disease and/or condition in the state of Kentucky, see ORI’s summary
sheet: “Reporting Requirements for Diseases and Conditions in Kentucky" [PDF].
HIV/AIDS Research: There are additional IRB requirements for designing and implementing the research and for obtaining
informed consent. Describe additional safeguards to minimize risk to subjects in the space provided below.
For additional information, visit the online IRB Survival Handbook to download a copy of the "Medical IRB's requirements for
Protection of Human Subjects in Research Involving HIV Testing" [D65.0000] [PDF], and visit the Office for Human Research
Protections web site for statements on AIDS research, or contact the Office of Research Integrity at 859-257-9428.
PI-Sponsored FDA-Regulated Research
Is this an investigator-initiated study that:
1) involves testing a Nonsignificant Risk (NSR) Device, or
2) is being conducted under an investigator-held Investigational New Drug (IND) or Investigational Device Exemption (IDE)?
Yes
No
PI-Sponsored FDA-Regulated Research
If the answer above is yes, then the investigator assumes the regulatory responsibilities of both the investigator and sponsor. The
Office of Research Integrity provides a summary list of sponsor IND regulatory requirements for drug trials [PDF], IDE regulatory
requirements for SR device trials [PDF], and abbreviated regulatory requirements for NSR device trials [PDF]. For detailed
descriptions see FDA Responsibilities for Device Study Sponsors or FDA Responsibilities for IND Drug Study Sponsor-
Investigators.
Describe the experience/knowledge/training (if any) of the investigator serving as a sponsor (e.g., previously held an
IND/IDE); and
Indicate if any sponsor obligations have been transferred to a commercial sponsor, contract research organization (CRO),
contract monitor, or other entity (provide details or attach FDA 1571).
IRB policy requires mandatory training for all investigators who are also FDA-regulated sponsors (see Sponsor-Investigator
FAQs). A sponsor-investigator must complete the applicable Office of Research Integrity web based training, (drug or device)
before final IRB approval is granted.
Has the sponsor-investigator completed the mandatory PI-sponsor training prior to this submission?
Yes
No
If the sponsor-investigator has completed equivalent sponsor-investigator training, submit documentation of the content for the
IRB’s consideration. 
Attachments
Section 9 Page 8 of 8
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HIPAA
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Is HIPAA applicable?
Yes
No
(Visit ORI's Health Insurance Portability and Accountability Act (HIPAA) web page to determine if your research falls under the HIPAA
Privacy Regulation.)
If yes, check below all that apply and attach the applicable document(s): 
HIPAA De-identification Certification Form
HIPAA Waiver of Authorization
Attachments
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STUDY DRUG INFORMATION
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The term drug may include:
FDA approved drugs,
unapproved use of approved drugs,
investigational drugs or biologics,
other compounds or products intended to affect structure or function of the body, and/or
complementary and alternative medicine products such as dietary supplements, substances generally recognized as safe (GRAS)
when used to diagnose, cure mitigate, treat or prevent disease, or clinical studies of e-cigarettes examining a potential therapeutic
purpose.
Does this protocol involve a drug including an FDA approved drug; unapproved use of an FDA approved drug; and/or an
investigational drug?
Yes
No
If yes, complete the questions below. Additional study drug guidance.
LIST EACH DRUG INVOLVED IN STUDY IN THE SPACE BELOW
Drug Name:
Note: Inpatient studies are required by Hospital Policy to utilize Investigational Drug Service (IDS) pharmacies (Oncology or
Non-Oncology). Use of IDS is highly recommended, but optional for outpatient studies. Outpatient studies not using IDS
services are subject to periodic inspection by the IDS for compliance with drug accountability good clinical practices. 
Indicate where study drug(s) will be housed and managed:
Investigational Drug Service (IDS) UK Hospital
Other Location:
Is the study being conducted under a valid Investigational New Drug (IND) application?
Yes
No
If Yes, list IND #(s) and complete the following:
IND Submitted/Held by:
Sponsor:
Held By:
Investigator:
Held By:
Other:
Held By:
Checkmark if the study is being conducted under FDA’s Expanded Access Program (e.g., Treatment IND)
or if this is an Individual Patient Expanded Access IND (FDA Form 3926).
FDA's Expanded Access Program Information for Individual Patient Expanded Access INDs, and attach the
following:
FDA Form 3926;
FDA expanded access approval or correspondence;
Confirmation of agreement from manufacturer or entity authorized to provide access to the product.
For guidance and reporting requirements at the conclusion of treatment see the Expanded Access SOP.
Complete and attach the required Study Drug Form picking "Study Drug Form" for the document type. Any
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applicable drug documentation (e.g., Investigator Brochure; approved labeling; publication; FDA correspondence,
etc.) should be attached using "Other Drug Documentation" for the document type.
Attachments
Section 11 Page 2 of 2
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STUDY DEVICE INFORMATION
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A DEVICE may be a:
component, part, accessory;
assay, reagent, or in-vitro diagnostic device;
software, digital health, or mobile medical app;
other instrument if intended to affect the structure or function of the body, diagnose, cure, mitigate, treat or prevent disease; or
a homemade device developed by an investigator or other non-commercial entity and not approved for marketing by FDA.
For additional information, helpful resources, and definitions, see ORI's Use of Any Device Being Tested in Research web page.
Does this protocol involve testing (collecting safety or efficacy data) of a medical device including an FDA approved device,
unapproved use of an approved device, humanitarian use device, and/or an investigational device?
Yes
No
[Note: If a marketed device(s) is only being used to elicit or measure a physiologic response or clinical outcome, AND, NO data will
be collected on or about the device itself, you may answer “no” above, save and exit this section, (Examples: a chemo drug study
uses an MRI to measure tumor growth but does NOT assess how effective the MRI is at making the measurement; an exercise study
uses a heart monitor to measure athletic performance but no safety or efficacy information will be collected about the device itself, nor
will the data collected be used for comparative purposes against any other similar device).]
If you answered yes above, please complete the following questions.
LIST EACH DEVICE BEING TESTED IN STUDY IN THE SPACE BELOW
Device Name:
Is the study being conducted under a valid Investigational Device Exemption (IDE),
Humanitarian Device Exemption (HDE) or Compassionate Use?
Yes
No
If Yes, complete the following: 
IDE or HDE #(s)
IDE/HDE Submitted/Held by:
Sponsor:
Held By:
Investigator:
Held By:
Other:
Held By:
 Check if this is a Treatment IDE or Compassionate Use under the Food and Drug Administration (FDA)
Expanded Access program.
For Individual or Small Group Expanded Access, see FDA's Early Expanded Access Program Information,
and attach the following:
FDA expanded access approval or sponsor’s authorization;
An independent assessment from an uninvolved physician, if available;
Confirmation of agreement from manufacturer or entity authorized to provide access to the product.
For guidance and reporting requirements at the conclusion of treatment see the Medical Device SOP.
Section 12 Page 1 of 2
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Does the intended use of any research device being tested (not clinically observed) in this study meet the regulatory definition of
Significant Risk (SR) device?
Yes. Device(s) as used in this study presents a potential for serious risk to the health, safety, or welfare of a subject and (1) is
intended as an implant; or (2) is used in supporting or sustaining human life; or (3) is of substantial importance in diagnosing,
curing, mitigating or treating disease, or otherwise prevents impairment of human health; or (4) otherwise presents a potential
for serious risk to the health, safety, or welfare of a subject.
No. All devices, as used in this study do not present a potential for serious risk to the health, safety, or welfare of
subjects/participants.
Complete and attach the required Study Device Form, picking the "Study Device Form" for the document type. Any
applicable device documentation (e.g., Manufacturer information; patient information packet; approved labeling; FDA
correspondence, etc.) should be attached using "Other Device Documentation" for the document type.
Attachments
Section 12 Page 2 of 2
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RESEARCH SITES
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To complete this section, ensure the responses are accurate then click "SAVE".
A) Check all the applicable sites listed below at which the research will be conducted. If none apply, you do not need to check any
boxes.
UK Sites
UK Classroom(s)/Lab(s)
UK Clinics in Lexington
UK Clinics outside of Lexington
UK Healthcare Good Samaritan Hospital
UK Hospital
Schools/Education Institutions
Fayette Co. School Systems *
Other State/Regional School Systems
Institutions of Higher Education (other than UK)
*Fayette Co. School systems, as well as other non-UK
sites, have additional requirements that must be
addressed. See ORI's IRB Application Instructions -
Off-site Research web page for details.
Other Medical Facilities
Bluegrass Regional Mental Health Retardation Board
Cardinal Hill Hospital
Eastern State Hospital
Norton Healthcare
Nursing Homes
Shriner’s Children’s Hospital
Veterans Affairs Medical Center
Other Hospitals and Med. Centers
Correctional Facilities
Home Health Agencies
International Sites
Research activities conducted at performance sites that are not owned or operated by the University of Kentucky, at sites
that are geographically separate from UK, or at sites that do not fall under the UK IRB’s authority, are subject to special
procedures for coordination of research review. Additional information is required (see IRB Application Instructions - Off-
Site Research web page), including:
A letter of support and local context is required from non-UK sites. See Letters of Support and Local Context on the
IRB Application Instructions - Off-Site Research web page for more information.
Supportive documentation, including letters of support, can be attached below.
NOTE: If the non-UK sites or non-UK personnel are engaged in the research, there are additional federal and
university requirements which need to be completed for their participation. For instance, the other site(s) may need
to complete their own IRB review, or a cooperative review arrangement may need to be established with non-UK
Section 13 Page 1 of 2
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sites.
Questions about the participation of non-UK sites/personnel should be discussed with the ORI staff at (859) 257-
9428.
List all other non-UK owned/operated locations where the research will be conducted:
Describe the role of any non-UK site(s) or non-UK personnel who will be participating in your research.
Attachments
B) Is this a multi-site study for which you are the lead investigator or UK is the lead site?
Yes
No
If YES, describe the plan for the management of reporting unanticipated problems, noncompliance, and submission of protocol
modifications and interim results from the non-UK sites:
C) If your research involves collaboration with any sites and/or personnel outside the University of Kentucky, then it is considered
multisite research and IRB reliance issues will need to be addressed. This may include national multi-center trials as well local studies
involving sites/personnel external to UK. If you would like to request that the University of Kentucky IRB (UK IRB) serve as the lead
IRB for your study, or if you would like the UK IRB to defer review to another IRB, please contact the IRBReliance@uky.edu.
Section 13 Page 2 of 2
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RESEARCH ATTRIBUTES
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Indicate the items below that apply to your research. Depending on the items applicable to your research, you may be required to
complete additional forms or meet additional requirements. Contact the ORI (859-257-9428) if you have questions about additional
requirements.
Not applicable
Check All That Apply
Academic Degree/Required Research
Alcohol/Drug/Substance Abuse Research
Biological Specimen Bank Creation (for sharing)
Cancer Research
CCTS-Center for Clinical & Translational Science
Certificate of Confidentiality
Clinical Research
Clinical Trial - Phase 1
Clinical Trial
Collection of Biological Specimens for internal banking and use
(not sharing)
Community-Based Participatory Research
Deception
Educational/Student Records (e.g., GPA, test scores)
Emergency Use (Single Patient)
Gene Transfer
Genetic Research
GWAS (Genome-Wide Association Study) or NIH Genomic Data
Sharing (GDS)
Human Cells, Tissues, and Cellular and Tissue Based Products
Individual Expanded Access or Compassionate Use
International Research
Planned Emergency Research Involving Exception from
Informed Consent
Recombinant DNA
Registry or data repository creation
Stem Cell Research
Suicide Ideation or Behavior Research
Survey Research
Transplants
Use, storage and disposal of radioactive material and radiation
producing devices
Vaccine Trials
For additional requirements and information:
Cancer Research (MCC PRMC)
Certificate of Confidentiality (look up
"Confidentiality/Privacy...")
CCTS (Center for Clinical and Translational
Science)
Clinical Research (look up "What is the definition
of....)
Clinical Trial
Collection of Biological Specimens for Banking
(look up "Specimen/Tissue Collection...")
Collection of Biological Specimens (look up
"Specimen/Tissue Collection...")
Community-Based Participatory Research (look
up "Community-Engaged...")
Data & Safety Monitoring Board (DSMB)
*For Medical IRB: Service Request Form for
CCTS DSMB
Data & Safety Monitoring Plan
Deception*
*For deception research, also go to the E-IRB
Application Informed Consent section,
checkmark and complete "Request for Waiver
of Informed Consent Process"
Emergency Use (Single Patient) [attach
Emergency Use Checklist] (PDF)
Genetic Research (look up "Specimen/Tissue
Collection...")
Gene Transfer
HIV/AIDS Research (look up "Reportable
Diseases/Conditions")
Screening for Reportable Diseases [E2.0000]
(PDF)
International Research (look up "International &
Non-English Speaking")
NIH Genomic Data Sharing (GDS) Policy (PDF)
Planned Emergency Research Involving Waiver
of Informed Consent*
*For Planned Emergency Research Involving
Waiver of Informed Consent, also go to the E-
IRB Application Informed Consent section,
checkmark and complete "Request for Waiver
of Informed Consent Process"
Use, storage and disposal of radioactive material
and radiation producing devices
Section 14 Page 1 of 2
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Section 14 Page 2 of 2
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FUNDING/SUPPORT
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If the research is being submitted to, supported by, or conducted in cooperation with an external or internal agency or funding program,
indicate below all the categories that apply. 
Not applicable
Check All That Apply
Grant application pending
(HHS) Dept. of Health & Human Services
(NIH) National Institutes of Health
(CDC) Centers for Disease Control &
Prevention
(HRSA) Health Resources and Services
Administration
(SAMHSA) Substance Abuse and Mental
Health Services Administration
(DoJ) Department of Justice or Bureau of
Prisons
(DoE) Department of Energy
(EPA) Environmental Protection Agency
Federal Agencies Other Than Those Listed
Here
Industry (Other than Pharmaceutical
Companies)
Internal Grant Program w/ proposal
Internal Grant Program w/o proposal
National Science Foundation
Other Institutions of Higher Education
Pharmaceutical Company
Private Foundation/Association
U.S. Department of Education
State
Click applicable listing(s) for additional requirements and information:
(HHS) Dept. of Health & Human Services
(NIH) National Institutes of Health
(CDC) Centers for Disease Control & Prevention
(HRSA) Health Resources & Services Administration
(SAMHSA) Substance Abuse & Mental Health Services
Administration
Industry (Other than Pharmaceutical Companies) [IRB Fee Info]
National Science Foundation
(DoEd) U.S. Department of Education
(DoJ) Department of Justice or Bureau of Prisons 
(DoE) Department of Energy Summary and Department of Energy
Identifiable Information Compliance Checklist
(EPA) Environmental Protection Agency
Other:
Specify the funding source and/or cooperating organization(s) (e.g., National Cancer Institute, Ford Foundation, Eli Lilly
& Company, South Western Oncology Group, Bureau of Prisons, etc.):
 
KL2 Career Development Grant and
Markey Cancer Center
Add Related Grants
If applicable, please search for and select the OSPA Account number or Electronic Internal Approval Form (eIAF) #
(notif #) associated with this IRB application using the "Add Related Grants" button. 
If required by your funding agency, upload your grant using the "Grant/Contract Attachments" button.
Add Related Grants
Grant/Contract Attachments
Section 15 Page 1 of 2
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The research involves use of Department of Defense (DoD) funding, military personnel, DoD facilities, or other DoD resources.
(See DoD SOP and DoD Summary for details)
Yes
No
Using the “attachments” button (below), attach applicable materials addressing the specific processes described in
the DoD SOP.
DOD SOP Attachments
Additional Certification: (If your project is federally funded, your funding agency may request an Assurance/ Certification/Declaration
of Exemption form.) Check the following if needed:
Protection of Human Subjects Assurance/Certification/Declaration of Exemption (Formerly Optional Form – 310)
Assurance/Certification Attachments
Section 15 Page 2 of 2
59128

OTHER REVIEW COMMITTEES
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If you check any of the below committees, additional materials may be required with your application submission.
Does your research fall under the purview of any of the other review committees listed below? [If yes, check all that apply and attach
applicable materials using the attachment button at the bottom of your screen.]
Yes
No
Institutional Biosafety Committee
Radiation Safety Committee
Radioactive Drug Research Committee
Markey Cancer Center (MCC) Protocol Review
and Monitoring Committee (PRMC)
Graduate Medical Education Committee (GME)
Office of Medical Education (OME)
Additional Information
Institutional Biosafety Committee (IBC) - Attach required IBC
materials
Radiation Safety Committee (RSC) - For applicability, see
instructions and attach form
Radioactive Drug Research Committee (RDRC)
Markey Cancer Center (MCC) Protocol Review and Monitoring
Committee (PRMC)** - Attach MCC PRMC materials, if any, per
instructions.
Office of Medical Education (OME)
Graduate Medical Education Committee (GME)
Attachments 
** If your study involves cancer research, be sure to select "Cancer Research" in the "Research Attributes"
section. ORI will send your research protocol to the Markey Cancer Center (MCC) Protocol Review and Monitoring
Committee (PRMC). The MCC PRMC is responsible for determining whether the study meets the National Cancer Institute
(NCI) definition of a clinical trial and for issuing documentation to you (the investigator) which confirms either that PRMC
approval has been obtained or that PRMC review is not required. Your IRB application will be processed and reviewed
independently from the PRMC review.
Section 16 Page 1 of 1
59128

ADDITIONAL INFORMATION/MATERIALS
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Approval Letter Details:
If you wish to have specific language included in your approval letter (e.g., serial #, internal tracking identifier, etc…), type that
language in the box below exactly as it should appear in the letter. The text you enter will automatically appear at the top of all
approval letters, identical to how you typed it, until you update it. Don't include instructions or questions to ORI staff as those will
appear in your approval letter. If these details need to be changed for any reason, you are responsible for updating the
content of this field.
MR Changing PI to Kunos, Updating Consents vd 2/13/2023
Additional Materials:
If you have other materials you would like to include for the IRB's consideration, check all that apply and attach the corresponding
documents using the Attachments button below.
Detailed protocol
Dept. of Health & Human Services (DHHS) approved protocol (such as NIH sponsored Cooperative Group Clinical Trial)
Other Documents
Protocol/Other Attachments
Attach Type File Name
Protocol
MCC-20-MULTI-37. Amendment 1. 25NOV2020.pdf
NOTE: Instructions for Dept. of Health & Human Services (DHHS)-approved protocol]
If you have password protected documents, that feature should be disabled prior to uploading to ensure access for IRB review.
To view the materials currently attached to your application, click “All Attachments” on the left menu bar.
Section 17 Page 1 of 1
59128

MCC Protocol #: MCC-20-MULTI-37 
Version Date: 25.November.2020 
18 
PRECISION-NEC 
 
 
 
6. STUDY DESIGN AND STATISTICAL CONSIDERATIONS 
 
6.1 
Study Design and Endpoints 
 
This is a single-arm, pilot trial in patients with metastatic high grade large cell neuroendocrine 
carcinoma (HG-LCNEC) to study the feasibility of upfront NGS directed treatment in high grade 
neuroendocrine carcinomas. Tumor samples will receive next generation sequencing (NGS) 
profiling to classify the tumor as: small cell-like or non-small cell-like. Non-typeable cases will 
not be eligible for participation in this study, neither is small cell neuroendocrine carcinoma 
(HG-SCNEC). The systemic therapy regimen will be determined based on the NGS profile of 
the tumor. 
 
Feasibility is defined as being able to sequence the patient within 2 months of initial medical 
oncology visit and being able to assign into molecularly-defined cohorts (TP53 and RB1 co- 
mutated vs non-co-mutated). 
 
Secondary outcomes include ORR and progression-free survival (PFS). Radiological response 
will be assessed via RECIST Version 1.1 criteria (Appendix B) based on standard-of-care CT 
scans completed at q2 monthly intervals during treatment and q3 month during observation. PFS 
is defined from date of on study to the date of disease progression or death or date of last follow- 
up whichever occurs first. PFS will be assessed via standard-of-care CT scans (q2 month 
intervals during active treatment and q3 months during observation) as graded by RECIST 
Version 1.1 criteria for up to one year post-study enrollment. 
 
All patients who received anticancer therapy will be included in the toxicity and safety analysis. 
Incidence tables will be generated to summarize incidence of patients reporting at least one 
episode of each specific AE, the incidence of AE causing withdrawal from the study and 
incidence of SAE. The total number of episodes for each event reported (Frequency Table), the 
severity and attribution to study therapy of each episode reported (Severity Table and Attribution 
Table) will also be evaluated. 
 
Listings of AEs by patients will include the following information: time to onset, the duration of 
each AE, the severity of each AE, the relationship of the AE to study therapy, whether it was a 
serious AE (or not), and whether the AE caused withdrawal. Toxicities will be graded according 
to Common Toxicity Criteria (CTCAE) v5. 
 
6.2 
Sample Size/Accrual Rate 
 
We plan to enroll 15 patients on this pilot trial to study the feasibility of upfront NGS directed 
treatment in high grade neuroendocrine carcinomas and evaluate the ORR and progression-free 
survival. 
 
Feasibility is defined as being able to sequence the patient within 2 months of initial medical 
oncology visit and being able to assign into molecularly defined cohorts (TP53 and RB1 co- 
mutated vs non co-mutated). If more than 50% patients are not able to sequence within 2 months 

MCC Protocol #: MCC-20-MULTI-37 
Version Date: 25.November.2020 
19 
PRECISION-NEC 
 
 
 
of initial medical oncology visit or more than 50% patients are not able to assign into 
molecularly defined cohorts, the study will be deemed not feasible. No stopping rule is planned 
to stop enrollment based on feasibility. With 15 patients, the probability of unfeasible of the 
study is calculated with true unfeasibility probability p from 0.2 to 0.8 (Table 1). From this 
calculation we see if the true unfeasibility rate <0.5, the probability to declaim the trial 
unfeasible is low and if the true unfeasibility rate >0.5, the probability to declaim the trial 
unfeasible is high. 
 
Table 1: Probability of unfeasibility for this pilot study 
True 
prob. of 
unfeasible 
p=0.2 
p=0.3 
p=0.4 
p=0.5 
p=0.6 
p=0.7 
p=0.8 
Prob. of 
unfeasible 
0.0042 
0.050 
0.213 
0.50 
0.787 
0.950 
0.996 
 
The expected accrual rate is about 8 patients per year and accrual duration is approximately 2 
years, with an additional 1 year follow-up after the last patient is enrolled on the study for 
observation of disease progression. Thus, the total study duration is about 3 years. 
 
All patients who completed at least 2-cycle treatments will be evaluable for the ORR objective. 
Patients who fail to complete 2-cycles of the treatment due to toxicity or withdrawal from study 
will be excluded  from the ORR evaluation. All patients enrolled on the study will be evaluable 
for the PFS. 
 
6.3 
Study Cohorts 
 
Patients with large cell, HG-NEC will be enrolled into one of two cohorts, small cell-like or non- 
small cell-like cohorts, based on the next generation sequencing panel performed on the tumor 
sample. It is expected to enroll 6 patients for small cell-like subtype (40%) and 9 patients for 
non-small cell-like subtype (60%). 
 
6.4 
Analysis of Primary and Secondary Endpoints 
 
Percentage of patients who are able to sequence within 2 months of initial medical oncology visit 
will be estimated and percentage of patients who are able to assign into molecularly defined 
cohorts will be estimated for assessment of feasibility of the study. The ORR will be estimated 
with a standard error (SE). All patients will be followed until disease progression, death or end of 
study, whichever occurs first, for evaluation of PFS. The PFS will be estimated using Kaplan- 
Meier method for the entire cohort. Summary statistics will be provided for the analysis of 
potentially targetable mutations in high grade neuroendocrine carcinoma. 

Page 1 of 10 
2-13-2023 
Consent and Authorization to Participate in a Research Study 
 
KEY INFORMATION FOR MCC-20-MULTI-37: A Pilot Feasibility Study of Next Generation 
Sequencing-based stratification of front-line treatment of high-grade Neuroendocrine 
Carcinoma (Precision-NEC) 
 
We are asking you to choose whether or not to volunteer for a research study about using molecular analysis to 
guide treatment planning for patients with high-grade neuroendocrine cancer (HG-NEC). We are asking you to 
take part in this research because you have HG-NEC that has spread to other places in your body and your 
cancer cannot be cured by surgery. The purpose of this study is to use results of molecular analysis of your tumor 
tissue to inform treatment planning for your disease. 
 
This top sheet provides Key Information to help you decide whether to participate. More detailed information is 
provided after this page. Ask the research team questions. If you have questions later, contact information for Dr. 
Charles Kunos, MD, the researcher (i.e., Investigator) in charge of this study, can be found below.   
WHAT IS THE STUDY ABOUT AND HOW LONG WILL IT LAST?   
HG-NEC is an aggressive cancer and currently, there is no standard front-line treatment. The usual approach 
involves treatment with platinum-based chemotherapy. For some patients this works well but for many others it 
does not. Among patients who get the usual approach, about 5 out of 100 are free of cancer after 5 years.   
One of the ways doctors are trying to find better treatments is by looking at the cancer on a molecular level. We 
know that many drugs are effective only against cancers with certain tumor mutations. We also know that some of 
the tumor mutation patterns in HG-NEC seem very similar to patterns of other cancer types. There are treatments 
that work against those mutation patterns approved by the FDA for other cancer types. In this study, we will test 
the match of your tumor tissue’s mutation patterns to the mutation patterns found in other cancer types. We will 
then recommend the FDA-approved treatment for you based on your tumor mutations profile. We hope this 
molecularly-guided plan for treatment will be more effective against your cancer (high-grade neuroendocrine 
cancer) than just the usual approach using platinum-based chemotherapy. 
Of course, getting the tumor analysis done and reviewing treatment options takes time. By doing this feasibility 
study, we hope to find out if we can complete molecular analysis (sequencing) and begin your treatment in a 
timely manner. Additionally, we want to learn how effective this approach will be. Your participation in this 
research study will last about 3 years.   
WHAT ARE KEY REASONS YOU MIGHT CHOOSE TO VOLUNTEER FOR THIS STUDY? 
The treatment plan matched specifically for you should be more effective than the usual treatment approach you 
might otherwise receive, however, there may be no added benefit to you at all. For a complete description of 
benefits, refer to the Detailed Consent, found on the following pages. 
WHAT ARE KEY REASONS YOU MIGHT CHOOSE NOT TO VOLUNTEER FOR THIS STUDY? 
Next generation molecular sequencing is now standard of care for all patients with HG-NEC and you can get 
treatment for your cancer without being on this study. For a complete description of risks, refer to the Detailed 
Consent and/or Appendix. 
DO YOU HAVE TO TAKE PART IN THE STUDY? 
If you decide to take part in the study, it should be because you really want to volunteer. You will not lose any 
services, benefits or rights you would normally have if you choose not to volunteer to be in this study.  
WHAT IF YOU HAVE QUESTIONS, SUGGESTIONS OR CONCERNS? 
If you have questions, suggestions, or concerns regarding this study or you want to withdraw from the study 
contact Charles Kunos, MD of the University of Kentucky Department of Radiation Medicine at 859-562-0210  
If you have any concerns or questions about your rights as a volunteer in this research, contact staff in the 
University of Kentucky (UK) Office of Research Integrity (ORI) between the business hours of 8am and 5pm EST, 
Monday-Friday at 859-257-9428 or toll free at 1-866-400-9428. 
IRB Approval
2/14/2023
IRB # 59128
IRB3

Page 2 of 10 
MCC-20-Multi-37 
 
              
Consent-HIPAA dated 2/13/2023 
 
 
DETAILED CONSENT: 
ARE THERE REASONS WHY YOU WOULD NOT QUALIFY FOR THIS STUDY? 
You cannot be in this study if you are under 18 years of age or if you are pregnant or nursing an infant.  
WHERE WILL THE STUDY TAKE PLACE AND WHAT IS THE TOTAL AMOUNT OF TIME INVOLVED? 
The research procedures will be conducted at UK Medical Center. You will need to come to the clinic every 4 
weeks while you are getting treatment. You will get treatment as long as the treatment helps you and you want to 
continue. You will come to clinic for another visit 30 days after you finish treatment. Each of these visits will take 
about 2 hours. You will be in the study for about 3 years.  
WHAT WILL YOU BE ASKED TO DO? 
If you decide to take part in this study, while you are receiving the commonly-used, platinum-based 
chemotherapy, your tumor tissue will be sent to a laboratory for molecular sequencing. Those results will be 
analyzed by the Markey Cancer Center Molecular Tumor Board and results will be provided to your oncologist. 
Based on your cancer’s molecular profile you may then be changed to a different FDA-approved treatment 
regimen that best matches the patterns of your tumor’s mutations. 
You will get the FDA-approved treatment for your cancer based on your tumor’s molecular profile. While on 
treatment, you will come to the clinic every 4 weeks. At each visit you will meet with your doctor and the research 
team and have a physical exam and laboratory tests (e.g., blood tests). You will get a CT scan every 2 months 
during study treatment. This study will collect information about how you are responding to the treatment. 
You will take the recommended treatment until your disease gets worse or the side effects become too severe.  
After you finish your study treatment, your doctor will continue to follow your progress every 3 months through 
clinic visits. During the follow-up period, you will get CT scan every 3 months for at least one year. Additionally, 
your research team will monitor you for potential side effects and worsening of your condition in conjunction with 
your oncologist until the study is completed.    
There are no additional tests or procedures for this study. You will have the same tests and visits on this study as 
you would have if you were not on study. For a list of all tests and procedures for this study, see the Appendix: 
Study Visits/Procedures.  
WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS? 
Physical: 
You will not receive any investigational treatment on this study.  
There is no additional physical risk from collecting leftover tumor tissue from a procedure that is being done as 
part of your clinical care.  
Risks of blood collection:  
Risks associated with blood sampling are generally slight, but may include soreness, bruising, pain, infection, 
possible fainting, bleeding.  
Risk of having genetic testing:  
Even without your name or identifiers, genetic information is unique to you making it possible for someone to 
trace it back to you. The results of genetic research apply to both you and your family members.  In some cases, 
it could be used to make it harder for you to get or keep a job or health insurance.  Genetic information could be 
used in ways that could cause you or your family distress.  There is a federal law called the Genetic Information 
Non- discrimination Act (GINA).  Generally, GINA makes it illegal for health insurance companies, group health 
plans, and most employers to discriminate against you or treat you differently based on your genetic information. 
Be aware that GINA does not protect you against discrimination by companies that sell life insurance, disability 
insurance, or long-term care insurance.  GINA also does not prohibit discrimination on the basis of an already 
known genetic disease. 
Unknown Risks 
In addition to the risks listed above, you may experience a previously unknown risk or side effect. Tell the study 
doctor or study staff right away if you have any problems or ill effects from participating in this study.  The 
59128

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MCC-20-Multi-37 
 
              
Consent-HIPAA dated 2/13/2023 
 
 
information in this form tells you what is known about the research study at the time this consent is first signed.  If 
any new information is discovered during the research study that may affect whether you want to continue to take 
part, you will be informed in a timely manner.  
WILL YOU BENEFIT FROM TAKING PART IN THIS STUDY? 
We do not know if you will get any benefit from taking part in this study. However, if you take part in this study, 
information learned may help others with your condition. 
IF YOU DON’T WANT TO TAKE PART IN THE STUDY, ARE THERE OTHER CHOICES? 
If you do not want to take part in the study, there are other choices.  
• 
You may choose to have cancer treatment without being on study. At UK, our standard treatment would 
be platinum-based chemotherapy with carboplatin and etoposide.  
• 
You may choose to take part in a different research study, if one is available. 
• 
You may choose not to be treated for cancer. 
• 
You may choose to only get comfort care to help relieve your symptoms and not get treated for your 
cancer.   
WHAT WILL IT COST YOU TO PARTICIPATE? 
You and/or your insurance company, Medicare, or Medicaid will be responsible for the costs of all care and 
treatment that you would normally receive for any conditions you may have. These are costs that are considered 
medically necessary and will be part of the care you receive, even if you do not take part in this study. 
The University of Kentucky may not be allowed to bill your insurance company, Medicare, or Medicaid for the 
medical procedures done strictly for research. These costs will be paid by the Markey Cancer Center. The 
research-related tests/procedures for this study are: review by the Molecular Tumor Board and some of the 
laboratory tests. 
WHO WILL SEE THE INFORMATION THAT YOU GIVE? 
When we write about or share the results from the study, we will write about the combined information. We will 
keep your name and other identifying information private. We will make every effort to prevent anyone who is not 
on the research team from knowing that you gave us information, and what that information is. Your information 
will be stored in a password-protected database and any physical files (scans, slides or paper records) will be 
stored in locked file cabinets located behind locked doors.   
You should know that in some cases we may have to show your information to other people. For example, the law 
may require us to share your information with:  
• 
a court or agencies, if you have a reportable disease/condition; 
• 
authorities, if you report information about a child being abused; or if you pose a danger to yourself or 
someone else.  
To ensure the study Is conducted properly, officials of the National Cancer Institute, the Kentucky Cancer 
Registry and/or the University of Kentucky may look at or copy pertinent portions of records that identify you. 
CAN YOU CHOOSE TO WITHDRAW FROM THE STUDY EARLY? 
You can choose to leave the study at any time. You will not be treated differently if you decide to stop taking part 
in the study. 
If you choose to leave the study early, data collected until that point will remain in the study database and may not 
be removed.  
The investigators (researchers overseeing this trial) may need to remove you from the study. You may be 
removed if: 
• 
you are not able to follow the directions, 
• 
we find that your participation in the study is more risk than benefit to you, or  
• 
the agency paying for the study chooses to stop this study early for a number of scientific reasons.  
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ARE YOU PARTICIPATING, OR CAN YOU PARTICIPATE, IN ANOTHER RESEARCH STUDY AT THE SAME 
TIME AS PARTICIPATING IN THIS ONE? 
You may not take part in this study if you are currently involved in another research study. It is important to let 
your study doctor know if you are in another research study. You should discuss this with your study doctor before 
you agree to participate in another research study while you are in this study. 
WHAT HAPPENS IF YOU GET HURT OR SICK DURING THE STUDY? 
If you believe you are hurt or if you get sick because of something that is due to the study, you should call Dr. 
Charles Kunos, MD at (859) 562-0210immediately. If you need to call on the weekend or after normal business 
hours, please call the UK paging operator at (859) 323-5321 and ask them to page the oncologist on-call. The 
oncologist will contact Charles Kunos, MD if necessary. Charles Kunos, MD or your treating oncologist will 
determine what type of treatment, if any, is best for you at that time. 
It is important for you to understand that the University of Kentucky does not have funds set aside to pay for the 
cost of any care or treatment that might be necessary because you get hurt or sick while taking part in this study. 
Also, the University of Kentucky will not pay for any wages you may lose if you are harmed by this study.   
Medical costs related to your care and treatment because of study-related harm will be your responsibility. 
These costs may be paid by your insurer if you are insured by a health insurance company (you should ask your 
insurer if you have any questions regarding your insurer’s willingness to pay under these circumstances). If you 
have any questions regarding Medicare/Medicaid coverage, you should contact Medicare by calling 1-800-
Medicare (1-800-633-4227) or Medicaid 1-800-635-2570. 
A co-payment/deductible may be needed by your insurer or Medicare/Medicaid even if your insurer or Medicare/ 
Medicaid has agreed to pay the costs. The amount of this co-payment/deductible may be costly. 
You do not give up your legal rights by signing this form. 
WILL YOU RECEIVE ANY REWARDS FOR TAKING PART IN THIS STUDY? 
You will not receive any rewards or payment for taking part in the study.  
WHAT IF NEW INFORMATION IS LEARNED DURING THE STUDY THAT MIGHT AFFECT YOUR DECISION 
TO PARTICIPATE? 
We will tell you if we learn new information that could change your mind about staying in the study. We may ask 
you to sign a new consent form if the information is provided to you after you have joined the study.  
WILL YOU BE GIVEN INDIVIDUAL RESULTS FROM THE RESEARCH TESTS? 
Generally, tests done for research purposes are not meant to provide clinical information. We will not provide 
you with individual research results.  
There is a slight possibility that during a research project, an investigator could discover something that could 
affect the health of you or your family. If this occurs, the finding will be reviewed by Markey’s Molecular Tumor 
Board to determine if it is in your best interest to contact you. 
Do you give permission for us to contact you about research results or  incidental findings that are determined to 
be important to you/your family’s health? (Incidental findings are unforeseen findings discovered during the 
course of the research that may affect you or your family’s health). 
 
Yes      No          _________Initials 
You may also withdraw your consent to be contacted with information about research results or incidental 
findings by sending a written request to Charles Kunos, MD Telephone: (859) 562-0210 at University of 
Kentucky c/o Markey Cancer Center Clinical Research Organization / CC 140 Pavilion H / 800 Rose Street / 
Lexington, KY 40536-0293. 
 
WHAT ELSE DO YOU NEED TO KNOW? 
If you volunteer to take part in this study, you will be one of about 15 people to do so.   
The Markey Cancer Center is providing financial support and/or material for this study. 
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Consent-HIPAA dated 2/13/2023 
 
 
A description of this clinical trial will be available on ClinicalTrials.gov as required by U.S. Law. This website will 
not include information that can identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 
WILL YOUR INFORMATION (OR SPECIMEN SAMPLES) BE USED FOR FUTURE RESEARCH? 
Your information or samples collected for this study will NOT be used or shared for future research studies, 
even if we remove the identifiable information like your name, medical record number, and/or date of birth.  
 
 
This Space Intentionally Blank 
 
 
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AUTHORIZATION TO USE OR DISCLOSE YOUR IDENTIFIABLE HEALTH INFORMATION  
The privacy law, HIPAA (Health Insurance Portability and Accountability Act), requires researchers to protect your 
health information. The following sections describe how researchers may use your health information.   
Your health information that may be accessed, used and/or released includes: 
• 
Demographic Information (your name, address, telephone number, email address, health insurance 
number, social security number; your birth month and year, gender, ethnic and racial background) 
• 
History and diagnosis of your disease 
• 
Specific information about treatments you have received 
• 
Past and present medical records pertaining to your health condition 
• 
Information about other medical conditions that may affect your treatment 
• 
Medical data, including physical examinations, laboratory test results, tumor measurements, CT scans, 
MRIs, X-rays, photographs of radiation therapy target areas, and pathology results related to your 
disease 
• 
Information on side effects (adverse events) you may experience, and how these were treated 
• 
Long-term information about your general health status and the status of your disease 
 
The Researchers may use and share your health information with: 
• 
The University of Kentucky’s Institutional Review Board/Office of Research Integrity; 
• 
Law enforcement agencies, when required by law; 
• 
University of Kentucky representatives; 
• 
UK Hospital, UK Markey Cancer Center; 
• 
U.S. Food and Drug Administration (FDA); 
• 
National Cancer Institute (NCI) and Kentucky Cancer Registry; 
• 
National Institutes of Health (NIH); 
If you become pregnant anytime during the study or within 90 days after stopping study treatment, you must 
inform the study doctor.  
The researchers agree to only share your health information with the people listed in this document.   
Should your health information be released to anyone that is not regulated by the privacy law, your health 
information may be shared with others without your permission; however, the use of your health information would 
still be regulated by applicable federal and state laws.   
You may not be allowed to participate in the research study if you do not sign this consent form. If you decide not 
to sign this form, it will not affect your: 
• 
Current or future healthcare at the University of Kentucky; 
• 
Current or future payments to the University of Kentucky; 
• 
Ability to enroll in any health plans (if applicable); or 
• 
Eligibility for benefits (if applicable). 
 
After signing the form, you can change your mind and NOT let the researcher(s) collect or release your 
health information (revoke the Authorization). If you revoke the authorization: 
Send a written letter to:  
Charles Kunos at University of Kentucky c/o Markey Cancer Center Clinical Research Organization /  
CC 140 Pavilion H / 800 Rose Street / Lexington, KY 40536-0293. 
• 
 to inform him of your decision. 
• 
Researchers may use and release your health information already collected for this research study. 
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Consent-HIPAA dated 2/13/2023 
 
 
• 
Your protected health information may still be used and released should you have a bad reaction 
(adverse event). 
You will not be allowed to review the information collected for this research study until after the study is 
completed. When the study is over, you may have the right to access the information. 
The use and sharing of your information has no time limit.  
If you have not already received a copy of the Privacy Notice, you may request one. If you have any 
questions about your privacy rights, you should contact the University of Kentucky’s Privacy Officer 
between the business hours of 8am and 5pm EST, Monday-Friday at (859) 323-1184. 
 
 
This Space Intentionally Blank 
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Appendix: Study Visits and Procedures  
Pre-Screening 
Baseline Visit 
Week 4 
Off-Treatment 
30-day follow-up  after the         
last dose * 
  ** Ongoing Follow-up          
(up to 1-yr post-enrollment) 
Off Study 
 
C
1 
D
1 
4 * 
8 * 
12 
* 
16 * 
CLIA-certified NGS 
ordered 
X 
 
Informed Consent 
X 
 
Demographics 
X 
 
ECOG Performance 
Status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 X 
Medical History 
X 
 
 
Record drug 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Physical Exam, with 
vital signs, weight 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
Adverse Event 
Evaluation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CBC w/ diff 1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CMP 2 
X 
X 
X 
X 
X 
X 
X 
B-hCG (in WCBP) 
X 
 
Imaging (CT C/A/P) 
X 
 
X 
X 
X3 
Assessment of 
disease progression 
X 
X 
X 
Record date of    
progression for PFS 
 Record the date of progression on the study form.  
Survival Status 
X 
 
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LEGEND for the STUDY CALENDAR: 
 
* data and samples may be collected ±1 week from this timeframe. 
** After the 16-week visit, Q4 weeks 1-year post study enrollment (i.e., the end of study observation period) or death, 
whichever occurs first.  
 
1. CBC w/diff: White Blood Cell count (WBC), Hematocrit (HCT), Platelet count, and Absolute Neutrophil Count (ANC). 
This panel will be run and assessed in timeframes per standard of care for the specific disease site of the neuroendocrine 
tumor.  
 
2. Serum Chemistry Panel (CMP) includes sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, 
albumin, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin. This panel will be run and assessed in 
timeframes per standard of care for the specific disease site of the neuroendocrine tumor. 
 
3. Imaging: Every 2 months during therapy to assess disease progression, and thereafter per standard of care (currently 
every 3 months) up to 1-year post-study enrollment.  There is a three-week window for imaging after Week 16, to allow 
for flexibility in patient scheduling and to avoid protocol deviations. 
 
4. Assessments to be made generally at the end of the week, with a one-week study visit window to allow for 
flexibility in patient scheduling. Study visit windows can flex up to 3 weeks, to avoid protocol deviations.  
5. For pregnancy testing in women of child-bearing potential: serum or urine tests are acceptable, and will be 
assessed in timeframes per standard of care for the specific disease site of the neuroendocrine tumor. 
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MCC-20-Multi-37 
 
              
Consent-HIPAA dated 2/13/2023 
 
 
INFORMED CONSENT :  SIGNATURES 
 
This consent includes the following: 
• Key Information Page 
• Detailed Consent  
• Appendix: Study tests and procedures 
 
You will receive a copy of this consent form after it has been signed. 
 
 
 
 
 
 
___________________________________________                      _____________________ 
Signature of research participant        
   
                                 Date 
 
 
 
 
 
 
 
 
 
___________________________________________ 
 
 
 
Printed name of research participant       
 
 
 
 
 
 
________________________________________________________________          ___________ 
Printed name of [authorized] person obtaining informed consent and  
HIPAA authorization)  
 
 
 
 
 
                           Date 
 
 
 
 
_____________________________________________ 
Signature of Principal Investigator or Sub/Co-Investigator  
 
 
 
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