Clinical trial NCT03289741
Conditions: Neuroendocrine Tumors
Keywords: Octreotide Lanreotide 17-422
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2017-09-19; Completion date: 2023-04-10
Enrollment: 51 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is being done to evaluate differences in patient experience during treatment with octreotide LAR and lanreotide.

Detailed description:

Arms: arm 1: Each patient on study will receive three injections of intramuscular (IM) octreotide Long Acting Release (LAR). Octreotide LAR for 3 injections followed by lanreotide for 3 injections arm 2: Each patient on study will receive three injections of deep subcutaneous (subq) lanreotide. Lanreotide for 3 injections followed by octreotide LAR for 3 injections
Interventions: intervention 1: Octreotide intervention 2: LAR Lanreotide intervention 3: Questionnaires
Intervention descriptions: intervention 1: Patients will receive three monthly injections every 28 (+/- 3) days. Octreotide LAR for 3 injections followed by lanreotide for 3 injections intervention 2: Patients will receive three monthly injections every 28 (+/- 3) days. Lanreotide for 3 injections followed by octreotide LAR for 3 injections intervention 3: Baseline questionnaire, Post-treatment questionnaire (after the first 3 injections), Preference questionnaire and Pain Score Diary.

Protocol documents:
Prot_SAP_000.pdf: 
Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
Page 1 of 28
 
 
 
 
 
A Pilot Study To Evaluate Patient Experience with the Somatostatin Analogs Octreotide Long Acting 
Release and Lanreotide during the Treatment of Advanced, Nonfunctional, Well Differentiated 
Neuroendocrine Tumors 
 
 
PROTOCOL FACE PAGE FOR 
MSK NON THERAPEUTIC PROTOCOL 
 
 
Principal Investigator/Department: 
Nitya Raj, MD 
Medicine 
Co-Principal  Investigator(s)/Department: 
Elizabeth Cruz, RN 
Leonard Saltz, MD
Medicine/Nursing 
Medicine 
Investigator(s)/Department: 
Ghassan Abou-Alfa, MD 
Andrea Cercek, MD 
Andrew Epstein, MD 
James Harding, MD 
David Ilson, MD, PhD 
Yelena Janjigian, MD 
David Kelsen, MD 
Nancy Kemeny, MD 
Geoffrey Ku, MD 
Eileen O’Reilly, MD 
Diane Reidy-Lagunes, MD 
Neil Segal, MD 
Armin Shahrokni, MD 
Anna Varghese, MD 
Rona Yaeger, MD 
Kenneth Yu, MD 
Elizabeth Won, MD 
Ellen Hollywood, NP 
Erica Kaufmann, NP 
Claudia Calderon, NP 
Pamela Vaiskauskas, RN 
Robin Brenner, RN 
Marinela Capagonu, PhD 
Jaclyn Norris, NP 
Michal Segal, RN 
Arlyn Apollo,MD 
Sree Chalasani, MD 
Daniel Danila, MD 
Avni Desai, MD 
Ping Gu, MD 
Afsheen Iqbal, MD 
Anuja Kriplani, MD 
Jia Li, MD 
Stuart Lichtman, MD 
Louise Ligresti, MD 
Parisa Momtaz, MD
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Nursing 
Nursing 
Nursing 
Nursing 
Nursing 
Biostatistics 
Nursing 
Nursing 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 
Medicine 


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Memorial Sloan Kettering Cancer 
Center IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
 
 
 
Azadeh Namakydoust, MD Medi
Isabel Preeshagul, DO 
Medi
Rui              Wang,              MD 
Medi 
Han               Xiao,               MD 
Medi 
Alice        Zervoudakis,         MD 
Medi 
Sippy             Punn,             RN 
Nurs 
Irina         Konzelmann,        NP 
Nurs 
Janet          Cogswell,          RN 
Nurs 
Kristen         O’Hagan,         NP 
Nurs 
Geri              Arnell,              RN 
Nurs 
Deaglan        McHugh,         MD 
Medi 
Eileen     Kilgus-     Reid,     NP 
Nurs 
Mary             Keogh,            RN 
Nurs 
Ofer           Maimran,           RN 
Nurs 
Megan             Stasi,            RN 
Nurs 
Colette          Owens,          MD 
Medi 
Marina         Shcherba,        DO 
Medi 
Catherine          Pires,          NP 
Nurs 
Jacintha        Ballingall,         NP 
N
 
Consenting  Professional(s)/Department: 
Ghassan       Abou-Alfa,       MD 
Medi 
Andrea          Cercek,          MD 
Medi 
Andrew          Epstein,          MD 
Medi 
James          Harding,           MD 
Medi 
David      Ilson,      MD,      PhD 
Medi 
Yelena         Janjigian,          MD 
Medi 
David            Kelsen,            MD 
cine 
cine 
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Page 3 of 28
Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
 
 
 
 
 
 
Leonard Saltz, MD
Medicine 
Armin Shahrokni, MD
Medicine 
Anna Varghese, MD
Medicine 
Rona Yaeger, MD
Medicine 
Kenneth Yu, MD
Medicine 
Elizabeth Won, MD
Medicine 
Ellen Hollywood, NP
Nursing 
Erica Kaufmann, NP
Nursing 
Claudia Calderon, NP
Nursing 
Elizabeth Cruz, RN
Nursing 
Audrey Chio, RN
Nursing 
Joseph Bacani, RN
Nursing 
Robin Brenner, RN
Nursing 
Michal Segal, RN
Nursing 
Jaclyn Norris, NP
Nursing 
Pamela Vaiskauskas, RN
Nursing 
Arlyn Apollo,MD
Medicine 
Sree Chalasani, MD
Medicine 
Daniel Danila, MD
Medicine 
Avni Desai, MD
Medicine 
Ping Gu, MD
Medicine 
Afsheen Iqbal, MD
Medicine 
Anuja Kriplani, MD
Medicine 
Jia Li, MD
Medicine 
Stuart Lichtman, MD
Medicine 
Louise Ligresti, MD
Medicine 
Parisa Momtaz, MD
Medicine 
Azadeh Namakydoust, MD
Medicine 
Isabel Preeshagul, DO
Medicine 
Rui Wang, MD
Medicine 
Han Xiao, MD
Medicine 
Alice Zervoudakis, MD
Medicine 
Sippy Punn, RN
Nursing 
Deaglan McHugh, MD
Medicine 
Colette Owens, MD
Medicine 
Marina Shcherba, DO
Medicine 
Pamela Drullinsky, MD
Medicine 
Zoe Goldberg, MD
Medicine 
Oscar Lahoud, MD
Medicine 
Kenneth Ng, MD
Medicine 
Tiffany Troso- Sandoval, MD
Medicine 
Maliha Nusrat, MD
Medicine 
 
 
Please Note: A Consenting Professional must have completed the mandatory Human Subjects 
Education and Certification Program. 


Page 4 of 28
Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
 
 
 
 
 
OneMSK  Sites 
Manhattan 
All Protocol Activities 
Basking Ridge 
All Protocol Activities 
Bergen 
All Protocol Activities 
Commack 
All Protocol Activities 
Monmouth 
All Protocol Activities 
Westchester 
All Protocol Activities 
Nassau 
All Protocol Activities 
 
 
 
 
 
 
 
 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 


Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
Page 5 of 28 
 
 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ........................................................................ 6 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS ................................................................................. 7 
3.0 
BACKGROUND AND RATIONALE ....................................................................................... 8 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION ................................................................. 13 
4.1 
Design .................................................................................................................................. 13 
4.2 
Intervention .............................................................................................................................. 14 
5.0 
CRITERIA FOR SUBJECT ELIGIBILITY ................................................................................. 14 
5.1 
Subject Inclusion Criteria ........................................................................................................ 15 
5.2 
Subject Exclusion Criteria ....................................................................................................... 15 
6.0 
RECRUITMENT PLAN ......................................................................................................................... 15 
7.0 
ASSESSMENT/EVALUATION PLAN .................................................................................. 15 
8.0 
TOXICITIES/SIDE EFFECTS .................................................................................................... 16 
9.0 
PRIMARY OUTCOMES ...................................................................................................... 18 
10.0 
CRITERIA FOR REMOVAL FROM STUDY ........................................................................ 19 
11.0 
BIOSTATISTICS ................................................................................................................. 20 
12.0 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
21 
12.1 
Research Participant Registration .......................................................................................... 21 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility .............. 21 
12.2 
Randomization ........................................................................................................................ 21 
13.0 
DAT A M ANAGEMENT ISSUES .......................................................................................... 22 
13.1 
Quality Assurance ................................................................................................................ 22 
13.2 
Data and Safety Monitoring .................................................................................................... 22 
14.0 
PROTECTION OF HUMAN SUBJECTS ............................................................................. 23 
14.1 
Privacy .................................................................................................................................. 23 
14.2 
Serious Adverse Event (SAE) Reporting ................................................................................ 24 
14.2.1  ........................................................................................................................................  25 
15.0 
INFORMED CONSENT PROCEDURES .................................................................................. 25 
16.0 
REFERENCES ........................................................................................................................... 26 
17.0 
APPENDICES ..................................................................................................................... 27 


Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
Page 6 of 28 
 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
Title of Study: A pilot study to evaluate patient experience with the somatostatin analogs  (SSA) octreotide long
acting  release  (LAR)  and  lanreotide   during   the  treatment  of  advanced,   nonfunctional,   well  differentiat ed 
neuroendocrine  tumors (WDNETs) 
Study Centers:  Memorial Sloan Kettering Cancer Center (MSKCC) 
Trial Phase: Pilot study 
Clinical Indication: Well differentiated  neuroendocrine  tumors  (WDNETs) 
Trial Type: Two-arm  randomized  design 
Type of control: No treatment control 
Route  of administration: Each patient  on study will receive  three  injections of  intramuscular  (IM) octreotide 
LAR and three injections of deep subcutaneous  (subq) lanreotide 
Trial blinding: No trial blinding 
Number of trial subjects:  50 patients
Estimated duration of trial: Approximately 30 months from the time the first subject signs the informed consent
until the final  consenting subject’s last visit 
Study Design: 
 
 
This will be a two-arm, randomized,  pilot study of 50 patients. Patients presenting with advanced  WDNETs, 
recommended  to begin SSA therapy by their provider,  will be eligible to participate.  As described in the 
protocol schema below, patients will be randomized to the order in which they receive  two standard-of-care 
SSA by monthly injection (i.e. octreotide LAR before  lanreotide,  or lanreotide  before octreotide LAR). 
Randomization  will occur centrally at MSKCC on day of protocol enrollment.  Our nursing staff will administer   
all injections; octreotide LAR will be manually prepped  in clinic just prior to injection, and lanreotide will be sent 
from pharmacy  in a prefilled syringe. Patients will receive  three monthly injections of one SSA (drug A),  
followed  by three monthly injections of the other SSA (drug B). 
 
The study participation period for each patient is 6 months from the date of beginning  treatment. There will be 
4 time periods: 
 
1. 
Pre-treatment  evaluation  on day of protocol enrollment  at which time a baseline questionnaire will be 
completed. 
2. 
SSA injections #1, 2, and 3 (with drug A) every  28 (+/- 3) days with numeric pain score (0 to 10) 
obtained in clinic and by diary following injection. 
3. 
SSA injections #4, 5, and 6 (with “drug B”) every  28 (+/- 3) days. 
4. 
End of study evaluation  after SSA injection #6, at which time a preference  questionnaire  will be 
completed by all patients. 
 
After completion of this study, if patients are recommended  to continue SSA therapy, they will continue on 
octreotide LAR moving  forward  which is on MSK formulary  without restrictions. 
 
We anticipate accrual of 1 to 2 patients per month, with accrual to this study completed in 24 to 36 months. 
Protocol  Schema: 


Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
Page 7 of 28 
 
 
 
 
Patients 
presenting 
with 
advanced, 
WDNETs, to 
be started on 
SSA 
 
 
Baseline 
assessme 
nts 
- Baseline 
questionn 
aire 
 
 
Central 
randomization 
at MSKCC 
(for order of 
injection) 
For 6 months: 
- 
Monthly 
SSA 
therapy 
 
(octreotide LAR 
lanreotide 
OR 
lanreotide 
octreotide LAR) 
- 
Pain Score 
after 
injections 1 
to 3 
 
 
 
th 
After 6 
injection: 
- 
Prefer 
ence 
questi 
onnair 
e 
 
 
 
 
 
 
 
2.1 
OBJECTIVES AND SCIENTIFIC AIMSOverview:  Octreotide  LAR has been used 
since the early  1990’s  to slow tumor growth.  The original  registration  was for control  of 
hormone-related  symptoms,  however  prolonged  progression-free  survival  (PFS) has been 
shown in a randomized,  double-blind,  placebo-controlled  trial.  However,  octreotide  LAR 
has not been specifically  registered  with the FDA for this specific  purpose. 
 
Based on the more recently  published  registration  trial,  lanreotide  has been specifically 
FDA-approved  for tumor control  of well differentiate d  NETs.  NCCN guidelines  regard  these 
two agents  as equally  acceptable  treatment  options. 
However,  the average  sales price 
(ASP) of one dose of octreotide  LAR is $3362,  while the ASP of lanreotide  is $6157.  These 
shots are given  every  4 weeks. So the annual  costs are $43,706  versus  $80,041,  or 
$36,335  per patient  per year.  This difference  is likely  to increase  further,  as generic 
versions  of octreotide  LAR are expected  on the market shortly.  Furthermore,  due to both 
increasing  incidence  and prevalenc e  of NETs, plus the fact that these agents  are often 
taken  for many years  by patients,  the potential  for financial  toxicity  associated  with 
lanreotide  is considerable. 
 
We believe  that the increased  cost of lanreotide  relative  to octreotide  LAR is not warranted, 
and on the GI Oncology  Service  we use octreotide  LAR unless there  is a specific  
contraindic ation  which favors  lanreotide.  Both agents  are on the MSK formulary  (lanreotide 
available  with restrictions) . 
 
A major marketing  point of lanreotide  is the claim that the injection  is more comfortable  for 
patients.  Octreotide  is given  as an intramuscular  injection,  while lanreotide  is given  as a 
“deep subq injection,”  although  the designation  of “deep”  subq is unique  to this agent  and 
is not well defined. We hypothesize  that patients  will find little  or no subjective  difference 
between  these two injections.  A demonstration  of this is likely  to have a significant  impact 
on the treatment  of NETs in practice in this country  and abroad.   There is considerable 
interest  in this  topic and this study within  the NET community. 


Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
Page 8 of 28 
 
 
 
The purpose of this study is to evaluate patient experience with the SSA octreotide LAR and 
lanreotide. In this study, patient experience is defined as the pain experienced with the drug 
injections, as octreotide LAR is administered IM, and lanreotide is administered deep subq. This 
will be directly evaluated through the primary objective. We will also try to further understand 
other aspects of patient experience by studying drug preference and financial toxicity with our 
secondary objectives. We have  developed our own questionnaires to study some of these 
secondary objectives, as there are no validated questionnaires available to address these issues 
for this patient population. 
 
 
Primary objective:  To compare injection  site pain  experienced with octreotide LAR and 
lanreotide. 
 
Primary endpoint: Comparison of mean pain score over the first three injections of either 
octreotide LAR or lanreotide. 
 
Secondary objectives: 
o To evaluate if patients have a preference for octreotide LAR or lanreotide. 
o To evaluate patient willingness to pay for preferred SSA therapy. 
o To quantify amount of time spent by nurses in clinic to prepare SSA injections. 
 
Secondary endpoints: 
o Patient-reported preference of octreotide LAR vs lanreotide assessed after six 
months of therapy by post-treatment questionnaire. 
o Patient-reported willingness to pay for preferred therapy, assessed by post- 
treatment questionnaire. 
o Nursing-reported measurement of time spent preparing SSA injections in clinic. 
 
3.1 
BACKGROUND AND RATIONALE 
 
3.2 
Well differentiated neuroendocrine tumors (WDNETs) 
 
WDNETs are an uncommon and heterogeneous group of neoplasms that arise throughout the 
body, most commonly in the lung and gastrointestinal tract.1  These tumors are subdivided into 
carcinoid tumors and pancreatic neuroendocrine tumors (panNETs); panNETs are the second 
most common tumor of the pancreas, and represent 1-2% of all pancreatic neoplasms.2,3 
Carcinoid tumors develop from the neuroendocrine tissues of the aerodigestive tract, and 
panNETs develop from the endocrine tissues of the pancreas (i.e. islets of Langerhans). This 
group of WDNETs is both morphologically and clinically distinct from high grade neuroendocrine 
carcinomas, tumors that are characterized by an extremely aggressive behavior and are treated 
along small cell lung cancer paradigms with platinum-based chemotherapy.4  Epidemiological data 
from the last 30 years has demonstrated that the incidence of NETs continues to rise, while there 
have been no significant changes in survival from this disease.5,6 
Although the majority of WDNETs are slow growing, after the development of metastatic disease 
(most commonly, in the liver), median survival ranges from 2 to 5 years, and most patients with 
liver metastases will die from disease.7 A subset of carcinoid tumors (less than 10%) and 
panNETs (just over 30%) are functional tumors and produce clinical syndromes due to excessive 
hormone secretion. Functional carcinoid tumors classically release serotonin and can cause 
“carcinoid syndrome.” The release of serotonin can cause hot red flushing of the face, severe 
diarrhea, and wheezing; rarely, the deposition of serotonin in the heart can cause cardiac 
disease.8  Functional panNETs are classified by the hormones they hypersecrete, and include 
insulinoma (secrete insulin and cause hypoglycemia), gastrinoma (secrete gastrin and cause 


Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
Page 9 of 28 
 
 
 
Zollinger-Ellison syndrome, which is characterized by severe peptic ulcer disease), glucagonoma 
(secrete glucagon and cause hyperglycemia), and vasoactive intestinal polypeptide (VIPoma, 
secrete VIP and cause severe secretory diarrhea).3,9-11   Non-functional WDNETs are tumors that 
do not secrete hormones or the products they secrete do not cause a clinical syndrome; 
examples include pancreatic polypeptide, chromogranin A, ghrelin, neurotensin, subunits of 
chorionic gonadotropin, and neuron-specific enolase.11  Metastatic disease is a common 
presentation for the majority of patients with WDNETs, especially those with non-functioning 
tumors given the absence of clinical symptoms that would warrant earlier clinical evaluation.7 
Asymptomatic patients diagnosed with advanced, metastatic WDNETs are often monitored 
initially, however with time, often their disease will progress and require treatment. The typical 
indications for therapy are pain and symptoms due to tumor bulk, symptoms from hormone 
secretion for functional tumors, high tumor burden, or progression of disease under observation.9 
Given the heterogeneous clinical presentations and complex spectrum of aggressiveness of 
WDNETs, their treatment is challenging, and requires multimodality management with surgeons, 
interventional radiologists, medical oncologists, endocrinologists and gastroenterologists. 
There are multiple systemic therapy options available for the treatment of metastatic WDNETs. 
These systemic options include SSA, targeted agents, and sometimes (usually in the setting of 
grade transformation) cytotoxic chemotherapy. SSA is often the first choice for treatment, and 
there are currently two options (both listed on NCCN guidelines): octreotide LAR or lanreotide. Of 
note, lanreotide is the only SSA that is approved by the FDA for the treatment of tumor control in 
non-functional gastroenteropancreatic NETs (GEP-NETs), based on the results of the CLARINET 
study (see Section 3.2.2). However, it is believed that octreotide LAR and lanreotide are 
biochemically similar, and at MSK, given the much higher retail price/institutional drug cost of 
lanreotide (see Section 3.2.3), lanreotide is not routinely offered to our patients. Lanreotide is 
currently available on the MSK formulary with restrictions; specifically, use of lanreotide requires 
approval from the P&T Chair or designee, and is restricted to patients receiving anticoagulation, 
or a personal history of bleeding from the intended injection site, or insufficient soft tissue mass. 
To date, no investigation has previously been undertaken to look at differences in one SSA  
versus the other. While it is believed that both octreotide LAR and lanreotide are biochemically 
similar and likely offer similar control of disease, these drugs differ in terms of mode of 
administration, and it has been suggested that this difference may impact patient experience and 
drug preference. The purpose of this study is to investigate the patient experience with these two 
SSA; we hypothesize that there is unlikely to be a meaningful difference, as octreotide LAR is 
administered IM,  and lanreotide is administered “deep subq.” However, if there is a meaningful 
difference in patient experience, with lanreotide being preferred by patients, we believe it could 
justify the higher cost of this drug to the institution and impact our use of lanreotide at MSK, when 
treating patients with WDNETs. We are limiting this study to patients with non-functional tumors to 
maintain a homogenous patient population, and to eliminate other biases that could impact patient 
experience. 
3.3 
Somatostatin analog therapy 
 
Somatostatin and its synthetic analogs (i.e. octreotide and lanreotide) bind to G-protein couple 
receptors on the cell surface to exert their effects. There are five known subtypes of somatostatin 


Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
Page 10 of 28
 
 
 
receptors, SST1-SST5, and binding of somatostatin to these receptors can inhibit the release of 
hormones and secretory proteins and also stall tumor growth, offering cytostatic control. 
The majority of WDNETs express somatostatin receptors (most commonly SST2) on their surface 
and are octreotide avid on SSA scintigraphy (i.e. OctreoscanTM).12,13    In octreotide positive 
disease, SSA are often used first line, as they are well tolerated, treat functional symptoms (in 
those tumors that are hormone secreting), and have been demonstrated to have an anti- 
proliferative, cytostatic effect on the growth of tumor. 
3.3.1 
SSA and control of symptoms  from hormone secretion 
 
Therapy with octreotide and lanreotide has revolutionized the way we care for patients with 
hormone producing, functional WDNETs. In the earliest study of SSA in patients with carcinoid 
syndrome, 25 patients with metastatic carcinoid tumors were treated with short-acting octreotide 
(150 mcg subq three times a day); 18/25 (72%) patients experienced a decrease of 50% or more 
in their urinary 5-HIAA levels, and 7/24 (29%) patients who reported flushing experienced 
complete relief of treatment, while 4/25 (16%) patients who reported considerable diarrhea 
experienced complete relief. In many subsequent studies, both partial and complete relief of 
carcinoid syndrome symptoms has been demonstrated in the majority of patients studied.14-20 
As previously discussed, functional panNETs include insulinomas, gastrinomas, glucagonomas, 
and VIPomas. SSA appear to be highly useful in the treatment of functional symptoms from 
VIPomas and glucagonomas, with an improvement seem in secretory diarrhea in VIPomas and 
an improvement in necrolytic migratory erythema, a characteristic blistering skin rash, in 
glucagonomas.21-23  However, although insulinomas and gastrinomas are the most common types 
of functional panNETs, SSA appear to have a more limited role in controlling their hormone- 
related symptoms. In particular, when initiating SSA therapy on insulinomas, close monitoring of 
glucose levels is required, as there can be transient worsening of hypoglycemia; hypoglycemia 
can occur as nearly half of insulinomas do not express SST2 and SSA therapy can blunt a 
compensatory glucagon response.9  In gastrinomas, rather than SSA, proton pump inhibitors are 
the preferred treatment to blunt the effects of excessive gastric acid production. 
3.3.2 
SSA and control of tumor growth 
 
In addition to treating hormone-related symptoms in functional tumors, octreotide and lanreotide 
have a role in controlling tumor growth of non-functional as well as functional tumors. As 
previously discussed, observation alone is generally pursued for patients with asymptomatic, 
advanced, unresectable WDNETs and small volume disease, as disease may remain indolent for 
months to years; SSA therapy is subsequently initiated when there is evidence of clinically 
meaningful tumor progression. 
The earliest studies investigating a cytostatic role for SSA included patients with many types of 
NETs. In one phase II trial, 34 patients with advanced NETs were treated with octreotide as 
antineoplastic therapy after clear objective disease progression; with a median follow-up of 29 
months, the median survival for this patient population from the start of octreotide therapy had not 
been reached.24 In this study, 17/34 (50%) patients had disease stabilization for a minimum of two 
months based on CT imaging. In another prospective study, 21 patients with metastatic GEP- 
NETs were treated with short-acting octreotide 200 micrograms three times a day; no patients 


Memorial Sloan Kettering Cancer Center 
IRB Number: 17-422 A(6) 
Approval date: 20-Apr-2020 
Page 11 of 28
 
 
 
had documented tumor shrinkage, and the most favorable response was stability of disease in 
5/21 (24%) patients.25 
The first randomized data to support an antiproliferative role for octreotide in the treatment of 
NETs came from the phase III PROMID study; this study included only midgut NETs and not 
panNETs.26  In this study, 85 patients were randomized to either placebo or octreotide LAR 30 mg 
IM every month until progression of disease or death. The primary endpoint was time to tumor 
progression (TTP), and the investigators observed a significant difference in TTP in the octreotide 
LAR and placebo groups (14.3 months versus 6 months, p=0.000072). In clinical practice and by 
NCCN guidelines, physicians were extrapolating the use of octreotide in midgut tumors to use in 
panNETs but no prospective randomized data exist.27 
The CLARINET study, however, confirmed the antiproliferative effect of SSA in GEP- NETs.[28]  
In this double-blind, placebo-controlled, multinational study in patients with low or intermediate 
grade, well or moderately differentiated NETs (45% panNETs), 204 patients were randomized to 
receive an extended-release aqueous-gel formulation of lanreotide (Autogel) at a dose of 120 mg 
or placebo once every 28 days for 96 weeks; the primary endpoint was progression-free survival 
(PFS), defined as time to disease progression or death. The authors observed that lanreotide was 
associated with significantly prolonged PFS in comparison to placebo (median not reached versus 
median of 18 months, p<0.001).There were no significant differences between the two groups in 
quality of life or overall survival. The most common adverse event was diarrhea, which was more 
prevalent in patients receiving lanreotide (26% in the lanreotide group and 9% in the placebo 
group). The CLARINET study confirmed that in comparison to placebo, lanreotide is safely 
tolerated and significantly prolongs PFS in patients with metastatic NETs; based on these  
findings, lanreotide is the only SSA that is FDA-approved for tumor control in non-functional 
GEP-NETs. 
 
Of note, while lanreotide is the only SSA FDA approved for cytostatic tumor control in the 
treatment of NETs (given the trial design of CLARINET and PROMID),  octreotide LAR is believed 
to have similar efficacy in controlling tumor growth based on the available data and identical 
mechanism of action of the two drugs.28  Per NCCN guidelines, either octreotide LAR or lanreotide 
are listed as treatment options for cytostatic control of octreotide avid disease. 
3.3.3 
Octreotide LAR vs lanreotide: similarities and differences 
 
Both octreotide LAR and lanreotide are 8 amino acid synthetic analogues of somatostatin. Both 
drugs have the same mechanism of action and are designed to bind the somatostatin receptor, 
but have a longer half-life than somatostatin. Both drugs display a greater affinity for the SST2 
and SST5 receptors. In the currently available formulations, both drugs are administered monthly. 
Although no trial has directly compared octreotide LAR and lanreotide for efficacy or tolerability, 
the assumption based on their mechanism of action is that the two drugs are identical, and 
similarly offer symptomatic and as well as cytostatic control in NETs. 
Though these drugs have many similarities biochemically, they differ in three key ways: 
preparation, mode of administration, and cost, which may influence patient experience and 
preference for drug. 
Preparation: Octreotide LAR is manually mixed in clinic; both the powder and diluents must first 


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reach room temperature, and then the powder must be completely saturated and uniformly 
suspended in the diluent immediately prior to injection. It is estimated by our nurses that this  
entire preparation period takes approximately seven minutes on average for each octreotide LAR 
injection administered in the clinic setting. To contrast, lanreotide is administered subcutaneously, 
and is an aqueous gel that comes in a prefilled syringe, requiring no in-clinic preparation. Given 
the very high volume of RN/nurse-only visits for SSA injections in our clinics providing care to  
NET patients, and the time requirements necessary to prepare octreotide LAR injections in 
specific, we now have a weekly clinic led by our nurses during which patients receive their 
monthly SSA injections. The amount of time spent by nurses preparing and mixing these 
injections while also assessing patients just prior to and after injection administration has never 
been quantified in a prospective fashion. 
Mode of administration: Octreotide LAR is administered IM while lanreotide is administered deep 
subq. It has been reported that up to 50% of patients receive injection site pain with octreotide 
LAR (with up to 5% developing hematomas at the injection site).[Reference: Octreotide LAR drug 
manual - Novartis] In comparison, about 20% of patients receiving lanreotide report injection site 
pain.[Reference: Lanreotide drug manual - Ipsen] This “injection site pain” has never been 
quantified from the patient’s perspective. However, on this limited data, it is assumed that 
lanreotide is less painful for patients, and may be the preferred SSA by patients; these 
assumptions have not been studied to date. 
Cost: There is also a cost difference between octreotide LAR and lanreotide, with an average 
sales price (as of October 2016) of approximately $3362 each month for a typical dose of 
octreotide LAR (20 mg) and $6157 each month for a typical dose of lanreotide (120 
mg).[Reference: Centers for Medicare and Medicaid Services Manufacturer reporting of Average 
Sales Price data]. Given the results of CLARINET, over the period of time a patient may be on 
lanreotide (>2 years), this cost differential in retail price of lanreotide could easily exceed $67,000 
per patient. 
Given increased cost-sharing, through co-payments, co-insurance, and high deductible insurance 
plans, all patients, including those who are well-insured, are at risk for experiencing the burden of 
high cost cancer treatments. Looking at US prices for new cancer drugs, these prices have  
soared from approximately $170 per month of therapy in the 1970s, to $10,000 per month as of 
2014.29  Through prior investigation, it has been shown that these higher drug costs can result in 
decreased adherence, increased bankruptcy, as well as personal sacrifice.30,31(National Survey of 
Households affected by Cancer) Looking specifically in advanced cancer patients, it has been 
demonstrated that 1 in 4 patients abandoned their cancer drugs when out-of-pocket costs 
exceeded $500 – a “side effect” of cancer treatment the American Society of Clinical Oncology 
(ASCO) has termed “financial toxicity.” 
In prior experience at MSK, when two drugs have demonstrable equal efficacy but real cost 
differences (for example in colorectal cancer: ziv-aflibercept and bevacizumab, cetuximab and 
panitumumab), we have recognized and acknowledged that there are not two equivalent 
regimens (i.e. offering all options and leaving the decision of which drug to use to the treating 
physician); rather, we have recognized there is really only one appropriate regimen, and neither 
ziv-aflibercept nor cetuximab are on our formulary and available for use by providers at MSK. 
Similarly, at this time, in an effort to control and limit costs, octreotide LAR is available on MSK 


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formulary for all patients and lanreotide is available on MSK formulary with restrictions, limited to 
those receiving anticoagulation, with a personal history of bleeding from the intended injection 
site, or with insufficient soft tissue mass to administer the shot. It is of note that MSK is one of the 
only institutions that does not have lanreotide freely available and current practice in the 
community and at other centers is changing to use lanreotide more frequently despite the higher 
retail price, particularly as it is now approved by the FDA for tumor control. Unlike the above 
examples in colorectal cancer, we recognize that the differences in drug administration between 
octreotide LAR and lanreotide could impact patient experience and drug preference. In our 
opinion, an improvement in patient experience could change the value of lanreotide (if lanreotide 
is in fact preferred by our patients), and impact our decision to use lanreotide without restrictions 
at MSK. For this reason, we have developed this pilot study, to evaluate the question “does 
patient experience impact choice for a particular SSA?” Given our belief that there is minimal 
difference in patient experience between an IM and deep subq injection, we hypothesize that 
there will not be a difference in patient experience between the two SSA to justify our inclusion of 
lanreotide onto the MSK formulary without restrictions. 
In order to answer the above question and study our hypothesis, this pilot study will evaluate the 
pain or discomfort experienced during SSA administration, to quantify the toxicity that may impact 
experience and drive patient drug preference. Through a questionnaire we have developed 
specific for this study (Appendix C), as there are no available validated questionnaires, patients 
will indicate their level of preference for these injections. In addition, we will study “financial 
toxicity,” and collect data on patient willingness to pay for a preferred drug. 
Ultimately, we believe that the findings from this pilot study will illustrate that patients will find little 
or no subjective difference between octreotide LAR and lanreotide injections. The data collected 
from this pilot study will be directly applicable in our practice here at MSK, and for the community 
of providers caring for patients with WDNETs, as well as for patients with this cancer. 
 
. 
 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.2 
Design 
 
This is a single institution, prospective, pilot study to evaluate pain experienced following 
injection and patient preference of SSA therapy when treated with octreotide LAR and 
lanreotide during the management of advanced WDNETs. Please refer to table 1 for the 
protocol design and schema: 
Table 1: Protocol schema 


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Patients 
presenting 
with 
advanced, 
WDNETs, to 
be started on 
SSA 
 
 
Baseline 
assessme 
nts 
- Baseline 
questionn 
aire 
 
 
Central 
randomization 
at MSKCC 
(for order of 
injection) 
For 6 months: 
- 
Monthly 
SSA 
therapy 
(octreotide LAR 
lanreotide 
OR 
lanreotide 
octreotide LAR) 
- 
Pain Score 
after 
injections 1 
to 3 
 
 
 
th 
After 6 
injection: 
- 
Prefer 
ence 
questi 
onnair 
e 
 
4.3 
Intervention 
 
This will be a two-arm randomized pilot study of 50 patients who will be randomized to 
receive octreotide LAR followed by lanreotide (n=25) or lanreotide followed by octreotide 
LAR (n=25). Patients presenting with advanced WDNETs, recommended to begin SSA 
therapy by their provider, will be eligible to participate. Patients will receive a total of 6 
months of SSA therapy on trial, three octreotide LAR injections and three lanreotide 
injections; the injections will be separated by 28 (+/- 3) days. For the purposes of this 
study, these drugs will be referred to as “drug A” (drug given in months 1 to 3) and “drug 
B” (drug given in months 4 to 6). Our nursing staff will administer all injections in the 
outpatient clinic setting; octreotide LAR will be manually prepped in clinic just prior to 
injection, and lanreotide will be sent from pharmacy to clinic in a prefilled syringe. 
On day of trial enrollment, after signing informed consent, patients will complete a baseline 
questionnaire (Appendix A). This baseline questionnaire will assess financial burden of 
health care, and whether a patient is concerned, prior to beginning any treatment, about 
pain or discomfort with the SSA injection. 
The study participation period for each patient is 6 months from the date of beginning 
treatment and includes 4 time periods (pre-treatment evaluation on day of protocol 
enrollment, monthly injections of drug A for three months, monthly injections of drug B for 
three months, and an end of study evaluation after injection #6 at which time a preference 
questionnaire will be completed).  At the first three visits when patients receive drug A, a 
pain score will be collected (0 to 10 numeric scale). Please refer to Appendix B for the 
post-treatment questionnaire that patients will complete immediately after injection, and to 
Appendix D for the diary patients will complete at home prior to returning for their next 
injection. As is standard practice at our institution, prior to every SSA injection, a baseline 
pain score using this same scale will be obtained by the nurse administering the injection. 
The end of study preference questionnaire (Appendix C) will evaluate which drug patients 
preferred and how much they preferred a certain drug. The preference questionnaire will 
also evaluate the topic of financial burden and willingness to pay, asking patients to 
quantify how much extra money per injection they believe their preferred drug is worth. 
5.0 
CRITERIA FOR SUBJECT ELIGIBILITY 


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5.1 
Subject Inclusion Criteria 
 
1. Willing and able to provide written informed consent for the trial 
2. ≥ 18 years of age 
3. Histologically- or cytologically- confirmed locally advanced or metastatic WDNET 
4. SSA therapy is recommended by physician for disease management, and has not yet 
begun 
5. ECOG performance status of 0, 1, or 2 
 
5.2 Subject Exclusion Criteria 
1. Currently participating in a study of an investigational agent 
2. Prior chemotherapy, targeted small molecule therapy within 2 weeks prior to study Day 
1 or not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a 
previously administered agent 
*Note: Subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to 
this criterion and may qualify for the study 
3. No concurrent chemotherapy or targeted small molecule therapy 
4. If received major surgery, not recovered adequately from the toxicity and/or 
complications from the intervention prior to starting the study 
5. Known additional malignancy that is progressing or requires active treatment 
6. Active infection requiring systemic therapy 
7. Known psychiatric or substance abuse disorders that would interfere with cooperation 
with the requirements of the trial 
 
 
6.0 
RECRUITMENT PLAN 
 
This study will be available to all patients seen at MSKCC, who meet the eligibility criteria 
outlined in section 5.0. 
 
Potential research subjects will be identified by doctors from the gastrointestinal medical 
oncology clinics at MSKCC. The principal investigator or a member of the treatment team 
will discuss the study with the patient. They will use the information provided by the patient 
and/or medical record to confirm that the patient is eligible and to contact the patient 
regarding study enrollment. All eligible patients, regardless of sex and race, will be 
approached for participation. The investigators are aware of the NIH policy concerning 
inclusion of women and minorities in clinical research populations. 
 
 
Participation in the study is completely voluntary. Patients will be required to read, agree 
to, and sign an IRB-approved informed consent form prior to registration on this trial; 
registration is described in section 12.2. Patients will not receive payment for their 
participation on this study. Patients are free to withdraw from the study without 
consequence at any time. 
7.1 
ASSESSMENT/EVALUATION PLAN 
 
The following assessments will be performed in this study: 


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Period
Screening 
(<28 days2) 
Treatment 
(6 SSA injections)1 
Post-treatment 
(After injection #6) 
Informed consent 
x 
 
 
Medical history
x 
 
 
Physical examination 
x 
 
 
Vital signs/Performance status3 
x 
 
 
Review and report medications
x
Central randomization at MSKCC (to order 
receiving octreotide LAR and lanreotide) after 
enrollment on study
 
x 
 
 
Octreotide LAR or Lanreotide injection  
x 
 
Baseline questionnaire (AppendixA)
x (day of 
protocol 
entry) 
 
 
 
 
Post-injection pain assessment (AppendixB) 
 
 
x 
(after injections 1, 2, 
and 3) 
 
 
 
Pain Diary (Appendix D) 
 
 
 
x 
 
End of study preference questionnaire 
(Appendix C)
 
 
x 
1. 
Each injection must be given 28 (+/-3) days apart 
2. 
Procedures must be performed within 28 days prior to first SSA injection 
3. 
Vital signs to include heart rate, respiratoryrate, blood pressure, height, and weight 
 
 
8.1 
TOXICITIES/SIDE EFFECTS 
 
There are no investigational drugs in this trial - both octreotide LAR and lanreotide are 
standard of care treatment options for WDNETs. Both octreotide LAR and lanreotide will 
be administered by their approved mode of administration (IM for octreotide LAR, deep 
subq for lanreotide). For these reasons, patients on this study are not anticipated to 
experience side effects or toxicities from these drugs beyond those that are already 
known. 
 
The side effects of octreotide LAR that may occur include: 
 
Common (>20%): 
 
 
Slow heart rate 
 
Fatigue, malaise 
 
Headache 
 
Fever 
 
Dizziness 
 
High blood sugar 
 
Abdominal pain 
 
Loose bowel movements 


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 
Nausea 
 
Flatulence 
 
Gallstones 
 
Upper respiratory infections 
Occasional (4-20%) 
 
Itching 
 
Muscle and/or joint aches 
 
High blood pressure 
 
Irregular heart rhythms 
 
Pain 
 
Rash 
 
Heartburn 
 
Fatty bowel movements 
 
Low red blood cell counts 
 
Ear aches 
 
Kidney stones 
 
Sweating 
 
Rare and Serious (<3%) 
 
Heart failure 
 
Depression 
 
Hallucinations 
 
Low blood sugars 
 
Difficulty swallowing 
 
Changes in taste 
 
Incontinence 
 
Tremor 
 
Vision changes 
 
Ringing of the ears 
 
Anaphylaxis 
 
Bile duct infection (cholangitis) 
 
Diabetes mellitus 
 
Fatty liver 
 
GI bleeding 
 
Pancreatitis 
 
Syncope/loss of consciousness 
 
The side effects of lanreotide that may occur include: 
 
Common (>20%): 
 
 
Diarrhea 
 
Abdominal pain 
 
Vomiting 
 
Gall stones 
 
Occasional (4-20%) 
 
Slow heart rate 
 
High blood pressure 


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 
Headache 
 
High or low blood sugars 
 
Flatulence 
 
Nausea 
 
Low red blood cell count 
 
Muscle or joint pains 
 
Dizziness 
 
Depression 
 
Loose bowel movements 
 
Constipation 
 
Rare and Serious (<3%) 
 
Gall bladder infection 
 
Hypersensitivity  reaction 
 
Low thyroid function 
 
Pancreatitis 
 
Cardiac valve abnormalities 
 
The interventions that are being performed in this trial, specifically, baseline, post- 
treatment, as well as preference questionnaires, do not pose any potential toxicities or 
side effects to enrolled patients. 
9.1 
PRIMARY OUTCOMES 
 
The following are tests and/or measures to be carried out during this pilot study: 
For patients: 
1. Baseline questionnaire: This questionnaire is provided in Appendix A and will be 
completed in clinic by all enrolled patients on the day that they provide informed 
consent to participate in this study. This questionnaire assesses financial burden of 
health care, and whether a patient is concerned, prior to beginning any treatment, 
about pain or discomfort with the SSA injection. 
 
2. Post-treatment questionnaire (after the first 3 injections): Patients will rate, on a 
numeric scale of 0 to 10, with 0 being “No pain” to 10 being “Worst pain ever” the pain 
or discomfort experienced with the SSA injection (Appendix B). Patients will rate their 
pain following injection by the nurse who administered the injection. 
 
3. Pain Score Diary: Patients will rate, on a numeric scale of 0 to 10, with 0 being “No 
pain” to 10 being “Worst pain ever” the pain or discomfort experienced with the SSA 
injection (Appendix D). Patients will rate their pain at home each day prior to returning 
to clinic for their next injection. 
 
4. Preference questionnaire: This questionnaire is provided in Appendix C. This 
questionnaire asks 2 questions to evaluate level of preference for drug A or B, and 
how much extra money per injection a patient feels the preferred drug would be worth. 


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For nursing: 
 
1.   Time for injection preparation: Nurses will use a stopwatch to measure the amount 
time they spend preparing octreotide LAR and lanreotide injections. Start time will be 
the time the RN opens the package of the drug; octreotide LAR injections will be 
prepared in the room while the patient is undergoing nursing assessment. The end  
time will be as soon as the nurse discards the needle in the sharps container. A secure 
data spreadsheet will be maintained on the MSK server to collect this information for 
each monthly injection for enrolled patients. Coordination of this study objective will be 
by Elizabeth Cruz, RN, Co-PI on this study. 
 
 
 
10.0 
CRITERIA FOR REMOVAL FROM STUDY 
 
In the absence of serious toxicity or complications, all patients will continue on study for 6 months 
(through completion of post-treatment questionnaire. In the absence of adverse event(s), patients 
may continue on study until one of the following criteria applies: 
 
 
Progression of disease warranting switch off of SSA therapy 
 
Development of an intercurrent medical condition or need for concomitant treatment that 
precludes further participation in the trial 
 
Unacceptable toxicity or any adverse event that precludes further participation in the trial 
 
The investigator removes the patient from the trial in the best interests of the patient 
 
Patient death 
 
Study completion or discontinuation for any reason 
 
Patient withdraws consent to continued participation in the trial or is lost to follow up 
 
If consent is withdrawn, the subject can continue to receive SSA therapy off of protocol under the 
care of his/her treating physician, however the subject will not receive any further study 
observation. 


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11.1 
BIOSTATISTICS 
 
This is a pilot study to evaluate patient preferences for therapy with the commercially available 
SSA octreotide LAR and lanreotide. Fifty patients with WDNETs will be accrued to this study. We 
expect to accrue 2-3 patients per month, with accrual completed in 24 months. This study is a 
two-arm randomized design, in which patients will be randomized to the order in which they 
receive octreotide LAR and lanreotide in six separate monthly injections (randomization described 
in section 12.2). 
Twenty-five patients will receive three monthly injections of octreotide LAR followed by three 
monthly injections of lanreotide, and 25 patients will receive three monthly injections of lanreotide 
followed by three monthly injections of octreotide LAR. The study participation period for each 
patient is 6 months from the date of beginning treatment and includes 4 time periods (pre- 
treatment evaluation on day of protocol enrollment, monthly injections of drug A for three months, 
monthly injections of drug B for three months, and an end of study evaluation after injection #6 at 
which time the preference questionnaire will be completed). Injection site pain will be assessed 
after each of the first 3 injections (with drug A) using a numeric 0 to 10 pain scale. For the primary 
objective of this study, all patients are expected to be included (i.e. all patients are expected to 
have data for the first 3 injections). In the unlikely event that patients drop-out before we get the 
data for the entire 6 months of this protocol, any patients that are removed will not be evaluable  
for our secondary objectives. 
Primary objective: To compare injection site pain experienced with octreotide LAR and 
lanreotide. 
 
Primary endpoint: Comparison of mean pain score over the first three injections of either 
octreotide LAR or lanreotide., With 25 patients per group, using a two-sample t-test we have 80% 
power to detect a mean score difference of 1.6 with a two-sided type I error of 0.05 assuming a 
standard deviation of 2 for both groups. The standard deviation of 2 was chosen based on internal 
pilot data of pain scores obtained from 20 patients receiving octreotide LAR. The mean score 
difference of 1.6 is the minimal detectable difference based on the proposed design and sample 
size and is considered to be clinically meaningful by the investigators of this study based on prior 
evaluation of the smallest meaningful and clinically significant change than can be identified using 
numeric and pictorial pain scales.34 For the actual analysis, nonparametric tests such as Wilcoxon 
rank sum test will be used to compare the two groups in terms of their pain scores averaged over 
the 3 time-points. To account for correlation between the pain scores obtained after injections 1,  
2, and 3, as a secondary analysis for the primary objective, repeated measures ANCOVA 
(adjusting for the baseline pain score) and/or Friedman’s test will also be employed. In this study, 
mean pain score will be calculated among all non-missing data. 
 
Secondary objectives: 
 
1. To evaluate if patients have a preference for octreotide LAR or lanreotide. 
 
2. To evaluate patient willingness to pay for preferred SSA therapy. 


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3. To quantify amount of time spent by nurses in clinic to prepare octreotide LAR and 
lanreotide  injections. 
 
 
Secondary endpoints: 
 
1. Patient-reported preference of octreotide LAR versus lanreotide assessed after 
six months of therapy by post-treatment questionnaire (Appendix C). Patients 
will be asked their level of preference for either drug A or B with a Likert scale 
(i.e. no preference for one drug over the other, mild preference for drug A, 
strong preference for drug A, mild preference for drug B, strong preference for 
drug B). Preference of one drug over the other will be summarized 
descriptively. 
 
2. Patient willingness to pay extra for preferred therapy measured in question 
format in the preference questionnaire (7 choices: $0, $1-50, $51-100, $101- 
200, $201-500, $501-1000, more than $1000). We will summarize patient 
willingness to pay (how much extra money per injection they believe the 
preferred drug is worth) using descriptive statistics after review of the answers 
provided in the preference questionnaire. We will use this data to evaluate 
whether or not the level of preference has a relationship to the amount of 
money people are willing to pay for a preferred therapy. This relationship will be 
assessed using the Spearman rank correlation coefficient. Due to small sample 
sizes this analysis is exploratory in nature. 
 
3. Measurement of time nurses spend preparing octreotide LAR injections in 
clinic. We will summarize the average (with range) of time spent preparing 
either octreotide LAR or lanreotide injections for the patients included in this 
study. 
 
 
12.1 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES 
 
12.2 
Research Participant Registration 
 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject Eligibility. 
 
Obtain informed consent, by following procedures defined in section entitled Informed 
Consent Procedures. 
During the registration process registering individuals will be required to complete a 
protocol specific Eligibility Checklist.The individual  signing the Eligibility Checklist is 
confirming whether or not the participant is eligible to enroll in the study. Study staff are 
responsible for ensuring that all institutional requirements necessary to enroll a participant 
to the study have been completed. See related Clinical Research Policy and Procedure 
#401 (Protocol Participant Registration). 
 
12.3 
Randomization 
 
This is a pilot study in which patients are randomized to the order in which they receive 
three monthly injections of octreotide LAR and lanreotide. After eligibility is established 


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and consent is obtained, patients will be registered in the Protocol Participant Registration 
(PPR) system, and randomized to order octreotide LAR lanreotide (n=25) or lanreotide 
octreotide LAR (n=25) using the Clinical Research Database (CRDBi-Multicenter). If a 
patient is pending registration based on limited available information, randomization will 
occur after all completed documentation is received. A patient may be registered as 
pending for up to 30 days from the initial registration submission to PPR. Randomization 
will be completed at MSKCC and accomplished by the method of random permutated 
block. Since this is an unblinded study, all study investigators may view randomization in 
the CRDBi-Multicenter. 
13.1 
DATA MANAGEMENT ISSUES 
 
A Research Study Assistant (RSA) will be assigned to the study. The responsibilities of the 
RSA include project compliance, data collection, abstraction and entry, data reporting, 
regulatory monitoring, problem resolution and prioritization, and coordinate the activities of 
the protocol study team. 
 
The data collected for this study will be entered into a secure database (Clinical Research 
Database, CRDB). Source documentation will be available to support the computerized 
patient record. 
 
13.2 
Quality Assurance 
 
Weekly registration reports will be generated to monitor patient accruals and completeness 
of registration data. Routine data quality reports will be generated to assess missing data 
and inconsistencies. Accrual rates and extent, and accuracy of evaluations and follow-up 
will be monitored periodically throughout the study period and potential problems will be 
brought to the attention of the study team for discussion and action. 
 
Random-sample data quality and protocol compliance audits will be conducted by the study 
team, at a minimum of two times per year, more frequently if indicated. 
 
 
13.3 
Data and Safety Monitoring 
 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan Kettering Cancer Center 
were approved by the National Cancer Institute in September 2001. The plans address the 
new policies set forth by the NCI in the document entitled “Policy of the National  Cancer 
Institute  for  Data  and  Safety  Monitoring   of  Clinical  Trials”  which  can  be  found  at:  
http://cancertrials.nci.nih.gov/researchers/dsm/index.html. The DSM Plans at MSKCC were 
established and are monitored by the Office of Clinical Research. The MSKCC Data and 
Safety 
Monitoring 
Plans 
can 
be 
found 
on 
the 
MSKCC 
Intranet 
at:  
http://mskweb5.mskcc.org/intranet/_assets/_tables/content/359689/Data_safety%20Monit   
oring07.pdf 
 
There are several different mechanisms bywhich clinical trials are monitored for data, safety 
and quality. There are institutional processes in place for quality assurance (e.g., protocol 
monitoring, compliance and data verification audits, therapeutic response, and staff 
education on clinical research QA) and departmental procedures for quality control, and 
there are two institutional committees that are responsible for monitoring the activities of our 


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clinical trials programs. The committees: Data and Safety Monitoring Committee (DSMC) 
for Phase I and II clinical trials, and the Data and Safety Monitoring Board (DSMB) for Phase 
III clinical trials, report to the Center’s Research Council and Institutional Review Board. 
 
During the protocol development and review process, each protocol will be assessed for its 
level of risk and degree of monitoring required. Every type of protocol (e.g., NIH sponsored, 
in-house sponsored, industrial sponsored, NCI cooperative group, etc.) will be addressed 
and the monitoring procedures will be established at the time of protocol activation. 
 
14.1 
PROTECTION OF HUMAN SUBJECTS 
 
All the patients will be required to sign an IRB-approved informed consent document and 
will have all their questions fully addressed before enrolling in the study. During the informed 
consent process, it will be made clear to the patient that participation is voluntary. All the 
data will be confidential, maintained in a password protected electronic database and will 
comply with all HIPAA  guidelines. 
 
Benefits: While on study, participating patients may identify a more preferable SSA drug 
and have the opportunity to receive this drug moving forward. It is also possible that from 
the results of this  pilot study, we will be able to characterize, in broader terms, patient 
preference for SSA therapy. This information may guide both patients and clinicians in the 
future when they are making a similar therapy decision (i.e. whether to begin octreotide LAR 
or lanreotide when needing to start a SSA). 
Risks: None beyond side effects/toxicities associated with SSA, which are standard-of-care 
therapy for WDNETs. 
Costs: The patient will be responsible for the costs of standard medical care, including all 
drug and drug administration fees and all hospitalizations, even for complications of 
treatment. Patients will be notified of the co-pay  associated with octreotide LAR and 
lanreotide and will have this information available prior to signing consent to this trial, as 
patients will have varying co-pays for these drugs that may impact their decision to enroll 
on this trial. 
 
Incentives:  No incentives will be offered to patients/subjects for participation in the study. 
 
Alternatives/options for treatment: Patients may be eligible for other investigational studies, 
standard treatment options (including SSA off of trial), or focus on palliative care options. 
Confidentiality:  Every effort will be made to maintain patient confidentiality. Research and 
hospital records are confidential. Patient’s name or any other personally identifying 
information will not be used in reports or publications resulting from this study. The Food 
and Drug Administration or other authorized agencies (e.g., qualified monitors) may review 
patients’ records and pathology slides, as required. 
14.2 
Privacy 
 
MSK’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure 


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of protected health information will be limited to the individuals described in the Research 
Authorization form. A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board (IRB/PB). 
14.3 
Serious Adverse Event (SAE) Reporting 
 
 
An adverse event is considered serious if it results in ANY of the following outcomes: 
 
Death 
 
A life-threatening adverse event 
 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 
 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
 
A congenital anomaly/birth defect 
 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition 
Note: Hospital admission for a planned procedure/disease treatment is not considered an 
SAE. 
 
SAE reporting is required as soon as the participant signs consent. SAE reporting is 
required for 30-days after the participant’s last investigational treatment or intervention. 
Any events that occur after the 30-day period and that are at least possibly related to 
protocol treatment must be reported. 
 
If an SAE requires submission to the IRB office per IRB SOP RR-408 ‘Reporting of Serious 
Adverse Events’, the SAE report must be sent to the IRB within 5 calendar days of          
the event. The IRB requires a Clinical Research Database (CRDB) SAE report be 
submitted electronically to the SAE Office as follows: 
For IND/IDE trials: Reports that include a Grade 5 SAE should be sent to  
saegrade5@mskcc.org.  All other reports should be sent to saemskind@mskcc.org. 
 
For all other trials: Reports that include a Grade 5 SAE should be sent to  
saegrade5@mskcc.org.  All other reports should be sent to sae@mskcc.org. 
 
The report should contain the following information: 
Fields populated from CRDB: 
 
Subject’s initials 
 
Medical record number 
 
Disease/histology (if applicable) 
 
Protocol number and title 
Data needing to be entered: 


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 
The date the adverse event occurred 
 
The adverse event 
 
The grade of the event 
 
Relationship of the adverse event to the treatment (drug, device, or intervention) 
 
If the AE was expected 
 
The severity of the AE 
 
The intervention 
 
Detailed text that includes the following 
o A explanation of how the AE was handled 
o A description of the subject’s condition 
o Indication if the subject remains on the study 
 
If an amendment will need to be made to the protocol and/or consent form 
 
If the SAE is an Unanticipated Problem 
The PI’s signature and the date it was signed are required on the completed report. 
For IND/IDE protocols: 
The CRDB SAE report should be completed as per above instructions.  If appropriate, the 
report will be forwarded to the FDA by the SAE staff through the IND Office. 
14.2.1 
There is no additional SAE reporting information as no investigational drug is being 
studied in this trial. 
15.1 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will explain 
full details of the protocol and study procedures as well as the risks involved to  
participants prior to their inclusion in the study. Participants will also be informed that they 
are free to withdraw from the study at any time. All participants must sign an IRB/PB- 
approved consent form indicating their consent to participate. This consent form meets the 
requirements of the Code of Federal Regulations and the Institutional Review 
Board/Privacy Board of this Center. The consent form will include the following: 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of 
supportive care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and 
to withdraw from participation at any time. 
Before any protocol-specific procedures can be carried out, the consenting professional 
will fully explain the aspects of patient privacy concerning research specific information.  In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 


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Each participant and consenting professional will sign the consent form. The participant 
must receive a copy of the signed informed consent form. 
16.0 
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17.0 
APPENDICES 
 
Appendix A: Baseline Patient Questionnaire 
Appendix B: Post-treatment Questionnaire 
Appendix C: Preference Questionnaire 


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Appendix D: Pain Score Diary