An Observational Pilot Study to Compare the Compliance With and Health Related Quality of Life During Therapy With Standard High-Dose Interferon Alfa (Intron A, HDI) Versus Pegylated Alfa-Interferon 2b (Sylatron, PEG IFN) in Patients With Surgically Resected Melanoma
Conditions: Melanoma
Sponsor: St. Luke's Hospital and Health Network, Pennsylvania

 
 
CLINICAL STUDY PROTOCOL 
An Observational Pilot Study to Compare the Compliance with and Health 
Related Quality of Life during Therapy with Standard High-Dose 
Interferon Alfa (Intron® A, HDI) versus Pegylated Alfa-Interferon 2b 
(Sylatron™, PEG IFN) in Patients with Surgically Resected Melanoma 
Protocol Number: 
MISP 50442 
Sponsor: 
Sanjiv Agarwala, MD 
Professor of Medicine, Temple University 
Chief Oncology & Hematology, St. Luke’s Cancer Center 
1600 Riverside Circle 
Easton, PA 18045 
Coordinating Organization: 
St. Luke’s University Health Network 
801 Ostrum Street 
Bethlehem, PA 18015 
Lead Investigator: 
Sanjiv Agarwala, MD 
Development Phase: 
IV 
Current Protocol Version and 
Release Date: 
Protocol Amendment (Version 2.0) 
25 March 2014 
 
Confidential 

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Signature Page 
PROTOCOL TITLE: 
An Observational Pilot Study to Compare the Compliance with 
and Health Related Quality of Life during Therapy with 
Standard High-Dose Interferon Alfa (Intron® A, HDI) versus 
Pegylated Alfa-Interferon 2b (Sylatron™, PEG IFN) in Patients 
with Surgically Resected Melanoma 
PROTOCOL NUMBER: MISP 50442 
 
Sanjiv Agarwala, MD 
Professor of Medicine, Temple University 
Chief Oncology & Hematology, St. Luke’s 
Cancer Center 
 
Date 

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Investigator Protocol Agreement Page 
I agree to conduct the study as outlined in the protocol entitled “An Observational Pilot Study 
to Compare the Compliance with and Health Related Quality of Life during Therapy with 
Standard High-Dose Interferon Alfa (Intron® A, HDI) versus Pegylated Alfa-Interferon 2b 
(Sylatron™, PEG IFN) in Patients with Surgically Resected Melanoma” in accordance with 
Good Clinical Practices as defined in the current requirements of ICH E6(R1) and local 
regulations. I have read and understand all sections of the protocol. 
 
 
Principal Investigator’s Name 
 
 
Principal Investigator’s Signature 
 
Date 
 
 

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Table of Contents 
Signature Page ............................................................................................................................ 2 
Investigator Protocol Agreement Page ....................................................................................... 3 
Table of Contents ................................................................................................................ 4 
List of Tables ....................................................................................................................... 6 
Protocol Synopsis ....................................................................................................................... 7 
List of Abbreviations and Definition of Terms ........................................................................ 10 
1 
Introduction ....................................................................................................................... 11 
1.1 
Background ............................................................................................................ 11 
1.2 
Study Rationale ...................................................................................................... 13 
2 
Study Objectives ................................................................................................................ 13 
2.1 
Primary Objective .................................................................................................. 13 
2.2 
Secondary Objectives ............................................................................................ 13 
3 
Study Design ..................................................................................................................... 13 
4 
Population .......................................................................................................................... 14 
4.1 
Inclusion Criteria ................................................................................................... 14 
4.2 
Exclusion Criteria .................................................................................................. 15 
5 
Treatments ......................................................................................................................... 15 
5.1 
Identity of Investigational Product ........................................................................ 15 
5.2 
Method of Assigning Patients to Treatment Groups ............................................. 15 
5.3 
Treatment Blinding ................................................................................................ 16 
5.4 
Management of Clinical Supplies .......................................................................... 16 
5.4.1 
Treatment Discontinuation and Premature Patient Withdrawal ............ 16 
5.4.2 
Early Study Termination ....................................................................... 16 
6 
Visit Schedule and Assessments ....................................................................................... 16 
6.1 
Patient Demographics/Baseline Characteristics .................................................... 19 
6.2 
Interferon Preference ............................................................................................. 19 
6.3 
ECOG Performance Scale ..................................................................................... 19 
6.4 
Weight and Vital Signs .......................................................................................... 19 
6.5 
Physical Examination ............................................................................................ 19 
6.6 
Clinical Laboratory Evaluations ............................................................................ 19 
6.7 
Treatment Perceptions and Health-Related Quality of Life Assessments ............. 19 
6.7.1 
CCSQ .................................................................................................... 20 
6.7.2 
FACT-BRM .......................................................................................... 20 
6.8 
Treatment Compliance ........................................................................................... 20 

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6.9 
Pregnancy .............................................................................................................. 20 
7 
Safety Monitoring .............................................................................................................. 21 
7.1 
Adverse Events ...................................................................................................... 21 
8 
Data Review and Database Management .......................................................................... 21 
8.1 
Site Monitoring ...................................................................................................... 21 
8.2 
Data Collection ...................................................................................................... 22 
8.3 
Database Management and Quality Control .......................................................... 22 
9 
Data Analysis ..................................................................................................................... 22 
9.1 
Compliance ............................................................................................................ 24 
9.2 
Safety ..................................................................................................................... 25 
9.3 
Sample Size Calculation ........................................................................................ 25 
9.4 
Interim Analysis ..................................................................................................... 25 
10 Ethical Considerations ....................................................................................................... 26 
10.1 
Regulatory and Ethical Compliance ...................................................................... 26 
10.2 
Informed Consent Procedures ................................................................................ 26 
10.3 
Responsibilities of the Investigator and IRB/EC ................................................... 26 
10.4 
Publication of Study Protocol and Results ............................................................ 27 
11 Protocol Adherence ........................................................................................................... 27 
11.1 
Protocol Amendments ........................................................................................... 27 
12 References ......................................................................................................................... 28 
13 Appendices ........................................................................................................................ 29 
13.1 
Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ) .................. 29 
13.2 
FACT-BRM (Version 4) ........................................................................................ 32 
13.3 
Interferon Preference Questionnaire ...................................................................... 36 
13.4 
ECOG Performance Scale ..................................................................................... 37 

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List of Tables 
Table 1: Study Treatment ......................................................................................................... 15 
Table 2: Schedule of Events (Cohort A: HDI) ......................................................................... 17 
Table 3: Schedule of Events (Cohort B: PEG IFN) .................................................................. 18 
 

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Protocol Synopsis 
Protocol Number: 
MISP 50442 
Title: 
An Observational Pilot Study to Compare the Compliance with and Health- 
Related Quality of Life during Therapy with Standard High-Dose Interferon 
Alfa (Intron® A, HDI) versus Pegylated Alfa-Interferon 2b (Sylatron™, 
PEG IFN) in Patients with Surgically Resected Melanoma 
Study Phase: 
IV 
Purpose/Rationale: 
To evaluate the compliance with and perceptions of treatment, as well as 
health-related quality of life (HRQOL) in surgically resected melanoma 
patients undergoing HDI or PEG IFN therapy. 
Study Population: 
Patients with surgically resected melanoma receiving adjuvant therapy with 
HDI or PEG IFN. 
Objectives: 
The primary objective of this study is: 
 To evaluate compliance with the administration of standard HDI 
versus PEG IFN for patients with melanoma in need of adjuvant 
therapy 
The secondary objectives of this study are: 
 To compare the convenience and satisfaction with chemotherapy for 
patients on standard HDI versus PEG IFN using a chemotherapy 
convenience and satisfaction questionnaire (CCSQ) and to evaluate the 
treatment-related side effects that may impact the patient’s HRQOL 
using the Functional Assessment of Cancer Therapy of Biologic 
Response Modifier (FACT-BRM) 
 To assess the frequency of Grade 3 and 4 toxicities, according to the 
National Cancer Institute (NCI) Common Toxicity Criteria for 
Adverse Events (CTCAE) for patients on standard HDI versus PEG 
IFN 
 To examine reasons for patients’ choice of treatment with HDI versus 
PEG IFN, for those cases in which patients are presented with a choice 
of either treatment option 
 To assess Health Resource Utilization on both arms of the study 
Treatments: 
 High-dose interferon alfa (Intron® A, HDI) 
 Pegylated alfa-interferon 2b (Sylatron™, PEG IFN) 
Study Design and 
Methodology: 
This will be a nonrandomized, open-label, pilot, observational, phase IV 
study to evaluate the compliance with and perceptions of treatment, as well 
as HRQOL in surgically resected melanoma patients undergoing HDI or 
PEG IFN therapy. The study will consist of a pretreatment (screening) 
phase, an induction phase, a maintenance phase, and an end-of-study (EOS) 
assessment. 
Pretreatment/Screening 
All patients will undergo a standard medical screening within 28 days of 
study of the first administration of HDI or PEG IFN. 
Induction Phase 

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All enrolled patients will be offered HDI or PEG IFN and, after discussion 
with their treating physician, will initiate the therapy of their choice. 
Suggested dosing per package insert is as follows, but can be altered per 
institutional guidelines. 
HDI: 
20 million IU/m2 as an intravenous (IV) infusion over 
20 minutes, 5 consecutive days per week for 4 weeks  
or 
PEG IFN: 6 mcg/kg/week subcutaneously (SC) for 8 doses 
 
Patients will complete the CCSQ and evaluate the treatment-related side 
effects that may impact their HRQOL using the FACT-BRM at specified 
time points during the Induction Phase.  
Maintenance Phase 
During the Maintenance Phase, patients will receive: 
HDI: 
10 million IU/m2 as an SC injection 3 times per week for 
48 weeks  
or 
PEG IFN: 3 mcg/kg/week SC for up to 5 years (only the first year of 
therapy will be evaluated in this study) 
This is again the suggested dosing per package insert, and can be altered per 
institutional guidelines. 
As in the Induction Phase, patients will complete the CCSQ and FACT-
BRM evaluations at specified time points. 
End-of-Study Assessment 
All patients who receive HDI or PEG IFN will be requested to return for an 
EOS visit within 21 days of discontinuation of study treatment. Final diary 
collection, safety assessments, treatment perceptions and HRQOL 
evaluations will be conducted at this visit. 
Safety assessments will be conducted during the study via clinical 
laboratory tests and adverse event (AE) monitoring. 
Inclusion Criteria: 
To be eligible for enrollment in this study, each of the following criteria 
must be satisfied with a “YES” answer (unless not applicable): 
1. Patient is a male or female at least 18 years of age 
2. Patient has had surgically resected melanoma and plans to receive 
adjuvant therapy with HDI or PEG IFN 
3. Patient is willing and able to give written informed consent 
4. Patient is willing to comply with all study requirements 
5. Female and male patients with female partners of child bearing 
potential that are using contraceptive methods 
Exclusion Criteria: 
To be eligible for this study, each of the following criteria must be satisfied 
with a “NO” answer: 
1. Patient is unable or unwilling to complete QoL questionnaires or 
compliance diary 
2. Patient has a history of anaphylaxis due to any interferon alpha 
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3. Patient has autoimmune hepatitis 
4. Patient has decompensated liver disease (Child-Pugh score >6 
[Class B and C]) 
5. Patient has a history of any neuropsychiatric disorder (including 
depression) that, in the judgment of the investigator, may impair the 
patient’s ability to successfully complete treatment or protocol-
related requirements (e.g., disorders that have required past 
hospitalization) 
6. Patients with uncontrolled cardiac disease or a history of a 
confirmed myocardial infarction within the last 6 months, 
uncontrolled diabetes mellitus, uncontrolled hyper or 
hypothyroidism and significant autoimmune disease requiring 
steroid therapy.  
 
Primary Endpoint: 
The primary endpoint is a comparison of compliance with administration of 
treatment to be evaluated through use of patient diaries. 
Secondary Endpoints: 
1. Comparison of patient-reported perceptions of treatment (CCSQ) and 
HRQOL (FACT-BRM) for each treatment arm 
2. Comparison of the frequency of Grade 3 and Grade 4 AEs per treatment 
arm 
3. Evaluation of the reasons for patients’ choice of treatment with HDI or 
PEG IFN through the use of a study-specific Interferon Preference 
Questionnaire, for cases in which patients are presented with a choice of 
either treatment option 
Safety Assessments: 
Safety assessments will include evaluation of AEs, clinical laboratory 
results (hematology and serum chemistry), vital sign measurements 
(temperature, blood pressure and pulse rate), and physical examination 
findings. 
Sample Size: 
100 patients 
Statistical Methods: 
This is an observational pilot study; therefore, descriptive outcomes will be 
presented comparing primary and secondary endpoints between patients 
receiving HDI versus PEG IGN. Selected inferential statistical comparisons 
will be conducted for exploratory purposes only and based on estimated 
clinically meaningful between-group differences, rather than statistically 
determined effect sizes.. 
Date of Protocol: 
Protocol Amendment (Version 2.0): 25 March 2014 
Original (Version 1.0): 27 June 2013 

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List of Abbreviations and Definition of Terms 
Abbreviation 
Definition 
AE 
adverse event 
CCSQ 
Chemotherapy Convenience and Satisfaction Questionnaire 
CRF 
case report form 
EC 
Ethics Committee 
ECOG 
Eastern Cooperative Oncology Group 
ECOG PS 
Eastern Cooperative Oncology Group Performance Status 
EORTC 
European Organization for Research and Treatment of Cancer 
FACT-BRM 
Functional Assessment of Cancer Therapy of Biologic Response Modifier 
FDA 
Food and Drug Administration 
HDI 
high-dose interferon 
ICH 
International Conference on Harmonization 
IFN 
interferon 
IRB 
Institutional Review Board 
IV 
intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI CTCAE 
National Cancer Institute Common Toxicity Criteria for Adverse Events 
OS 
overall survival 
PEG 
pegylated 
QoL 
quality of life 
QAS 
quality of life adjusted survival 
RFS 
relapse-free survival 
SC 
subcutaneous 
US 
United States 
 

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1 
Introduction 
1.1 
Background 
Melanoma 
The incidence of melanoma is rising rapidly, with over 75,000 new cases expected to occur in 
the United States (US) in 2013 (Siegel 2013). Despite this rising incidence, which is likely 
related to an increased emphasis on early detection, the mortality rate has remained relatively 
unchanged (Howlander 1975-2008). 
Most patients with melanoma present with early stage disease. For patients with thin 
melanomas without other adverse pathologic features, the cure rate with surgical therapy 
alone exceeds 90% (Sosman 2013). Unfortunately, for patients with thicker melanomas (stage 
IIb or higher), the risk of recurrence is higher. For these patients, the risk of recurrence is 
correlated with pathologic features, including thickness of the lesion, high versus low mitotic 
rate, presence of ulceration and regional lymph node involvement. High-risk disease is 
generally considered to include patients with stage IIb disease (lesion thickness >4 mm 
without ulceration or >2 mm with ulceration), stage IIc disease (lesion thickness >4 mm with 
ulceration), and stage III disease (regional lymph node involvement). 
Adjuvant therapy to reduce the risk of recurrence in high-risk patients has now become 
standard of care for patients with stage III disease and is often used clinically for patients with 
high-risk stage II disease. Currently, the Food and Drug Administration (FDA) approved 
adjuvant therapy for patients with high-risk non-metastatic melanoma is interferon alpha. 
Both the standard form (interferon alpha 2b) and pegylated interferon alpha are approved for 
use as adjuvant therapy. 
Interferon Alfa 
The use of high-dose interferon (HDI) as adjuvant therapy following surgical resection of 
high-risk melanoma began in the early 1990s. The Eastern Cooperative Oncology Group 
(ECOG) 1684 trial examined the efficacy of 1-year HDI in patients with stage IIb-III 
melanoma (Kirkwood 1996). Patients were randomly assigned to receive HDI at a schedule of 
20 MU/m2/day intravenously (IV) for 5 consecutive days for 4 weeks (induction) followed by 
10 MU/m2/day subcutaneously (SC) 3 times per week (maintenance) for 48 weeks or 
observation. HDI was shown in the first analysis to significantly increase median relapse-free 
survival (RFS) (1.7 years versus 1 year; p=0.0023) and to prolong median overall survival 
(OS) (3.8 years versus 2.8 years; p=0.0237). In a follow-up analysis, the difference in OS was 
no longer statistically significant; however, the improvement in RFS persisted. The 
prolongation of RFS was only clearly shown for patients with stage III disease; however, 
there were too few stage II patients in the trial to draw a meaningful conclusion regarding its 
benefit in this patient population. Similar results to those obtained in ECOG trial 1684 were 
seen in subsequent trials in high-risk patients including Intergroup trials E1690 and E1694. 
The results of these trials have established the treatment schedule from E1684 as a standard of 
care for the adjuvant therapy of high-risk melanoma. A subsequent trial (E1697) was also 
performed to compare 1 month of induction therapy to observation for patients with stage IIa 

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disease. Accrual to this trial was halted when a planned interim analysis showed no difference 
in RFS or OS. 
Pegylated Interferon Alfa (PEG IFN) 
PEG IFN is composed of interferon covalently bound to polyethylene glycol monomethoxy 
ether, which increases the stability of the compound and results in a mean half-life (t1/2) 
approximately 5 times greater than the t1/2 of HDI (Eggermont 2008). In 2011, the FDA 
approved the drug as adjuvant treatment for patients with surgically resected melanoma based 
on the outcome from the European Organization for Research and Treatment of Cancer 
(EORTC) 1991 study (Eggermont 2012). In this study, patients with stage III melanoma after 
complete regional lymphadenectomy were randomized to receive either PEG IFN at a dose of 
6 mcg/kg per week SC for 8 weeks followed by 3 mcg/kg per week SC for a treatment 
duration of up to 5 years or observation. At 7.6-year median follow-up, patients who received 
PEG IFN therapy had a significantly improved RFS; however, the distant metastasis free 
survival and OS were similar between the 2 cohorts (Eggermont 2012).  
Toxicity and Quality of Life on Interferon Therapy 
The use of adjuvant HDI is associated with considerable toxicity, most prominently flu-like 
symptoms and depression, resulting in a high rate of discontinuation. Despite this, over 60% 
of patients are able to complete 1 year of therapy. Treatment with PEG IFN produces similar 
side effects to those seen in patients treated with HDI, but at a lower intensity (Loquai 2008).  
The value of HDI adjuvant therapy, with its attendant side effects, is an area of interest for 
prescribing physicians. Investigators question whether patients view HDI treatment positively 
because there is only a modest benefit in RFS without an improvement in OS. In 2002, a 
study was conducted to evaluate quality of life (QoL) of high-risk melanoma patients who 
received HDI versus observation for patients enrolled on 2 cooperative group trials (E1684 
and E1690/S9111/C9190) (Kilbridge 2002). The study analyzed the trial efficacy, utility data, 
and quality-adjusted time without symptoms or toxicity to estimate the effect of HDI on QoL-
adjusted survival (QAS). When the study evaluated patients enrolled in the E1684 study, a 
significant increase in QAS was found for all patient subsets but the result was statistically 
significant for only 16% of patients. For patients enrolled in the E1690/S9111/C9190 trial, 
QAS improvement was seen for 77% and a decrease was seen for 23%. Neither of the groups 
was statistically significant. In both trials, the change in QAS depended more on the utility for 
HDI toxicity than on the utility for melanoma recurrence. 
A study has also been conducted to evaluate the effect of PEG IFN therapy on QoL. This 
study performed a retrospective evaluation using the EORTC QLQ-C30 QoL questionnaire. 
Both patients and physicians were asked to report on the patients’ physical condition, mental 
health, and social life at baseline and throughout the course of treatment. The dose of 
PEG IFN given was lower than the current standard, at 2 mcg/kg per week for 18 months. For 
all functional domains analyzed, patients reported a decrease from baseline in their ability to 
function while on PEG IFN treatment. Similarly, as expected, there was an increase in 
constitutional symptoms with fatigue and loss of appetite being the most highly affected. 
Despite the significant impact of treatment on the QoL, patients still assessed their QoL as 
good on PEG IFN treatment.  

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1.2 
Study Rationale 
Previous trials have examined the quality of life of patients on either HDI or PEG IFN; 
however, no trials have examined whether patients prefer HDI or PEG IFN therapy. This 
study is a pilot, nonrandomized, observational, Phase IV study to investigate the compliance 
with and perceptions of treatment, as well as health-related quality of life (HRQOL) in 
surgically resected melanoma patients undergoing HDI or PEG IFN therapy. Patients will be 
offered HDI and/or PEG IFN, and, after discussion with their treatment physicians, will 
initiate therapy of choice. Baseline data, including medical history, perceptions of treatment 
and HRQOL, will be collected upon enrollment. Patients will complete treatment perception 
and HRQOL questionnaires and drug administration diaries to track compliance and the 
overall well-being of the patient while on therapy. 
Accrual of 100 patients is expected to generate data adequate to determine whether a larger 
trial is warranted.  
2 
Study Objectives 
2.1 
Primary Objective 
 To evaluate compliance with the administration of standard HDI versus PEG IFN for 
patients with surgically resected melanoma in need of adjuvant therapy 
2.2 
Secondary Objectives 
 To compare perceptions of chemotherapy for patients on standard HDI versus PEG IFN 
using the Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ) and to 
evaluate the treatment-related side effects that may impact the patient’s HRQOL using the 
Functional Assessment of Cancer Therapy of Biologic Response Modifier (FACT-BRM) 
 To assess the frequency of Grade 3 and 4 toxicities, according to the National Cancer 
Institute (NCI) Common Toxicity Criteria for Adverse Events-CTCAE, Version 4.0 
 To examine the reasons for patients’ choice of treatment with PEG IFN versus HDI 
 To assess Health Resource Utilization on both arms of the study 
3 
Study Design 
This study is a non-randomized, observational, phase IV, multi-site pilot study to investigate 
the compliance with and perceptions of treatment, as well as HRQOL in surgically resected 
melanoma patients undergoing HDI or PEG IFN therapy. After discussion with their treating 
physician, patients will receive 1 of 2 approved adjuvant therapies for melanoma: 
1. Cohort A: high-dose interferon alfa (HDI, Intron® A) 
2. Cohort B: pegylated alfa-interferon 2b (PEG IFN, Sylatron™) 
Although the study is not randomized, in order to attempt to discern a difference between the 
groups, a maximum of a 60:40 split will be allowed on the protocol. This means that a 

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maximum of 60% of patients will be permitted on either arm and if achieved, that particular 
arm will be capped at 60%.  
Each treatment arm will have a pretreatment phase (within 4 weeks/28 days of starting the 
induction phase (4 weeks of HDI or 8 weeks of PEG IFN), a maintenance phase (treatment 
administration at specified times up to 1 year), and an end-of-study assessment, conducted 
within 21 days of discontinuation of study treatment. 
The primary endpoint of this study is to compare compliance with treatment of HDI and 
PEG IFN. Patients will complete drug administration diaries to track compliance with the 
recommended dosing schedule. Secondary endpoints include comparing treatment 
perceptions and HRQOL between treatment groups, comparing the frequency of Grade 3 
and Grade 4 adverse events (AEs) in each treatment arm, and evaluating the reasons for 
patients’ choice of treatment with HDI or PEG IFN through the use of the Interferon 
Preference Questionnaire 
 Patients receiving HDI will complete the CCSQ and FACT-BRM at baseline, every 2 weeks 
during the induction phase and monthly during the maintenance phase (beginning at Day 29) 
for up to 1 year. Patients receiving PEG IFN will complete the CCSQ and FACT-BRM at 
baseline, 2 weeks, 4 weeks, 6 weeks, and monthly during the maintenance phase (beginning at 
Day 57) for up to 1 year. Adverse events will be monitored throughout the study. Any dose 
adjustments based on toxicities will be made according to investigator judgment and the 
package insert for each product. Patients will also be queried to determine the most important 
reasons for choice of treatment with HDI versus PEG IFN. 
Study participation is expected to last until the completion of HDI treatment or a comparable 
duration for PEG IFN recipients (approximately 1 year). 
Safety and tolerability will be assessed by evaluating adverse events, clinical laboratory tests 
(hematology and serum chemistry), physical examination, and Eastern Cooperative Oncology 
Group Performance Status (ECOG PS). The schedule of events for each treatment arm is 
presented in Table 2 and Table 3. 
4 
Population 
The study population will consist of males and females at least 18 years of age with surgically 
resected melanoma in need of adjuvant therapy. Approximately 100 patients will be enrolled 
to compare the toxicity and compliance with standard HDI versus PEG IFN. This study is 
being conducted in the US at approximately 5-10 centers. 
The investigator must ensure that all patients who meet the following inclusion and exclusion 
criteria are offered enrollment in the study. 
4.1 
Inclusion Criteria 
1. Man or woman at least 18 years of age 
2. Patient has had surgically resected melanoma and plans to receive adjuvant therapy 
with HDI or PEG IFN 

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3. Patient is willing and able to give written informed consent 
4. Patient is willing to comply with all study requirements 
5. Female and male patients with female partners of child bearing potential must use 
adequate contraceptive measures while on treatment 
4.2 
Exclusion Criteria 
1. Patients were unable or unwilling to complete QoL or compliance questionnaires 
2. Patient has a history of anaphylaxis due to any interferon alpha product 
3. Patient has autoimmune hepatitis 
4. Patient has decompensated liver disease (Child-Pugh score >6 [Class B and C]) 
5. Patient has a history of any neuropsychiatric disorder (including depression) that, in 
the judgment of the investigator, may impair the patient’s ability to successfully 
complete treatment or protocol-related requirements (e.g., disorders that have required 
past hospitalization).  
6. Patients with uncontrolled cardiac disease or a history of a confirmed myocardial 
infarction within the last 6 months, uncontrolled diabetes mellitus, uncontrolled hyper 
or hypothyroidism and significant autoimmune disease requiring steroid therapy.  
5 
Treatments 
5.1 
Identity of Investigational Product 
Patients will be offered HDI and PEG IFN and, after discussion with their treating physician, 
will initiate the therapy of their choice (Table 1).The HDI and PEG IFN dose may modified 
per institutional dosing guidelines. 
Table 1: Study Treatment (Suggested Dosing per Package Insert) 
Treatment Group 
Dose 
Induction Phase 
Maintenance Phase 
High-dose interferon alpha 
(HDI) 
20 million IU/m2 IV infusion 
over 20 minutes, 5 consecutive 
days per week for 4 weeks 
10 million IU/m2 as a SC injection 3 times 
per week for 48 weeks 
Pegylated alfa-interferon 2b 
(PEG IFN) 
6 mcg/kg/week SC for 8 doses 
3 mcg/kg/week SC for up to 5 yearsa 
a this study will only examine the first year of treatment 
The proper storage conditions of HDI and PEG IFN will be described on the medication 
labels. 
5.2 
Method of Assigning Patients to Treatment Groups 
This is an open-label, nonrandomized study. Patients will be offered HDI and/or PEG IFN 
and, after discussion with their treating physician, will initiate the therapy of their choice. 

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5.3 
Treatment Blinding 
Not applicable for this study. 
5.4 
Management of Clinical Supplies 
Patients will receive commercially available product. 
5.4.1 
Treatment Discontinuation and Premature Patient Withdrawal 
The investigator may at any time determine that a patient should no longer receive treatment 
with HDI or PEG IFN for reasons related to patient safety or for other reasons. If a patient’s 
treatment with interferon is permanently discontinued, all study procedures will also be 
discontinued. All data obtained prior to treatment discontinuation will be included in the 
analysis set.  
Patients may voluntarily withdraw from the study for any reason at any time. They may be 
considered withdrawn if they state an intention to withdraw, or fail to return for visits, or 
become lost to follow up for any other reason. 
If premature withdrawal occurs for any reason, the investigator must determine the primary 
reason for a patient’s premature withdrawal from the study and record this information on the 
Study Completion case report form (CRF). Patients who are prematurely withdrawn from the 
study will not be replaced. 
5.4.2 
Early Study Termination 
The study can be terminated at any time for any reason by the sponsor. Should this be 
necessary, instructions will be provided concerning timing of final assessments. The 
investigator will be responsible for informing the Institutional Review Board (IRB) and/or the 
Ethics Committee (EC) of the early termination of the trial. 
6 
Visit Schedule and Assessments 
Table 2 and Table 3 are suggested assessments for both treatment arms and suggested visit 
procedures are indicated with an “x.” This study schedule is a suggested guideline and can be 
modified per institutional standard practice guidelines, with the exception of QoL, which is 
mandatory at the time points as indicated.

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Table 2: Schedule of Events Cohort A: HDI Suggested schedule of events (QOL evaluation is mandatory) 
Test/Assessment 
Pretreatmenta 
D1  
D8 b 
D15 b 
D22 b 
Maintenance Phasec 
Informed consent 
X 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
Interferon preference questionnaire 
X 
 
 
 
 
 
ECOG PS 
X 
 
 
 
 
 
Weight/vital signsd 
 
X 
X 
X 
X 
X 
Physical examinatione 
 
X 
 
 
 
X 
Hematology labsf 
 
X 
X 
X 
X 
X 
Chemistry labsg 
 
X 
X 
X 
X 
X 
Collection and Monitoring of 
Grade 3 and 4 AE  and all SAEs h 
 
X 
X 
X 
X 
X 
QoL evaluationsi 
 
X 
 
X 
 
X 
Drug administration diaryj 
 
X 
X 
X 
X 
X 
Treatment: 
Induction Phase: Suggested dosing per package insert is 20 million IU/m2 IV infusion over 20 minutes, 5 consecutive days per week for 4 weeks; Maintenance Phase: 10 
million IU/m2 SC injection 3 times per week for 48 weeks. Dosing can be modified per institutional guidelines. 
a Within 4 weeks (28 days) of starting HDI 
b For Days 8, 15, and 22, if HDI was delayed, the study assessment schedule for these dates will also be delayed 
c . Maintenance dose begins at day 29 and then monthly until last dose of HDI. 
d Weight should be obtained at baseline. Vital signs should be performed at each visit.  
e  Physical examination should be performed monthly or according to institutional protocol. 
f Hematology labs will be done as clinically indicated and will include hemoglobin, hematocrit, RBC count, WBC count, platelets , as well as total and differential neutrophil counts. 
Hematology labs should be performed weekly during the induction phase or according to institutional protocol.  
g Chemistry labs will be done as clinically indicated and should include albumin, creatinine kinase (CPK), urea or blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), lactate dehydrogenase (LDH), serum alkaline phosphatase, direct and total bilirubin, glucose, total protein, sodium, potassium, chloride, bicarbonate 
(HCO3) (CO2; venous blood), calcium, and phosphorous. Chemistries should be performed weekly during the induction phase or according to institutional protocol. Specific individual 
chemistry labs may be omitted according to investigator judgment if not included in the institution’s chemistry profile.  
h All Grade 3 and 4 adverse events (regardless of whether they occur on treatment or non-treatment weeks) will be collected until the last day of treatment and submitted utilizing the 
corresponding AE forms. Additionally, all SAEs, regardless of grade will also be collected. 
i Treatment perceptions and HRQOL data will be collected via CCSQ and FACT-BRM, respectively, at baseline, every 2 weeks during the induction phase, and monthly during the 
maintenance phase (beginning at day 29) for up to 1 year. These questionnaires are to be completed prior to the administration of the dose for that visit. .If dose is held or changed QoL 
is still to be completed.   
j Patients will be instructed to record details on the receipt of HDI in the drug administration diary and will return the diary to the site at the subsequent visit. These diaries will capture the 
onset of AEs in relationship to the day of drug administration. 
 

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Table 3: Schedule of Events (Cohort B: PEG IFN) Suggested schedule of events (QOL evaluation is mandatory) 
Test/Assessment 
Pretreatmenta 
D1  
D8 b 
D15 b 
D22 b 
 
 b 
 b 
b 
Maintenance Phasec 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Interferon preference questionnaire 
X 
 
 
 
 
 
 
 
 
 
ECOG PS 
X 
 
 
 
 
 
 
 
 
 
Weight/vital signsd 
 
X 
X 
X 
X 
 
 
 
 
X 
Physical examinatione 
 
X 
 
 
 
 
 
 
 
X 
Hematology labsf 
 
X 
X 
X 
X 
 
 
 
 
X 
Chemistry labsg 
 
X 
X 
X 
X 
 
 
 
 
X 
Collection and Monitoring of 
Grade 3 and 4 AE  and all SAEs h 
 
X 
X 
X 
X 
 
 
 
 
X 
QoL evaluationsi 
 
X 
 
X 
 
 
 
 
 
X 
Drug administration diaryj 
 
X 
X 
X 
X 
 
 
 
 
X 
Treatment: 
Induction Phase: Suggested dosing per package insert is 6 mcg/kg/week SC for 8 doses (8 weeks); Maintenance Phase: 3 mck/kg/week SC injection for up to 5 years (this 
study will only evaluate the first year of treatment). Dosing can be modified per institutional guidelines. 
a Within 4 weeks (28 days) of starting PEG IFN 
b For Days 8, 15, 22, 29, 36, 43, and 50 if PEG IFN was delayed, the study assessment schedule for these dates will also be delayed 
c Maintenance dose begins at day 29 and then monthly until last dose of PEG IFN, .or until treatment discontinuation or one year of therapy 
d  Weight should be obtained at baseline. Vital signs should be performed at each visit.  
e  Physical examination should be performed monthly or according to institutional protocol. 
f Hematology labs will be done as clinically indicated and will include hemoglobin, hematocrit, RBC count, WBC count, platelets , as well as total and differential neutrophil counts.. 
Hematology labs should be performed weekly during the induction phase or according to institutional protocol.  
g Chemistry labs will be done as clinically indicated and should include albumin, creatinine kinase (CPK), or urea blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), lactate dehydrogenase (LDH), serum alkaline phosphatase, direct and total bilirubin, glucose, total protein, sodium, potassium, chloride, bicarbonate 
(HCO3) (CO2; venous blood),  calcium, and phosphorous. Chemistries should be performed weekly during the induction phase or according to institutional protocol. Specific individual 
chemistry labs may be omitted according to investigator judgment if not included in the institution’s chemistry profile.  
h All Grade 3 and 4 adverse events (regardless of whether they occur on treatment or non-treatment weeks) will be collected until the last day of treatment and submitted utilizing the 
corresponding AE forms. Additionally, all SAEs, regardless of grade will also be collected. 
i Treatment perceptions and HRQOL data will be collected via CCSQ and FACT-BRM, respectively, at baseline, 2 weeks, 4 weeks, 6 weeks, and monthly during the maintenance phase 
(beginning at Day 57) for up to 1 year. These questionnaires are to be completed prior to the administration of the dose for that visit. If dose is held or changed, QoL is still to be 
completed. 
j Patients will be instructed to record details on the receipt of HDI in the drug administration diary and will return the diary to the site at the subsequent visit. These diaries will capture the 
onset of AEs in relationship to the day of drug administration. 
 
 

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Patients should be seen for all visits on the designated day or as close as possible to the 
designated day. Please note that the ±1 week interval in the Maintenance Phase of the 
study is proposed as a guide. Visits falling outside this window should not lead to 
automatic patient discontinuation. 
All data obtained from the assessments listed in the schedule of events must be supported in 
the patient’s source documentation. 
6.1 
Patient Demographics/Baseline Characteristics 
Patient demographic and baseline characteristic data will be collected for all patients enrolled 
in the study, including relevant medical history. 
6.2 
Interferon Preference 
For situations in which the investigator offered both treatment options, patients will be 
queried regarding their reasons for the choice of either HDI or PEG IFN using a standardized 
questionnaire created for this study (see Appendix 13.3). 
6.3 
ECOG Performance Scale 
The Eastern Cooperative Oncology Group Performance Scale (ECOG PS) assesses the 
patients' general well-being and activities of daily life (see Appendix 13.4). 
6.4 
Weight and Vital Signs 
Weight and vital signs (temperature, pulse rate and blood pressure) should be recorded at 
baseline. Vital signs should be obtained weekly during induction and monthly during 
maintenance or according to institutional protocol.  
6.5 
Physical Examination 
A complete physical examination will be performed at baseline and monthly for the duration 
of the study or according to institutional protocol. The physical examination should include 
examination of general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, 
lungs, heart, abdomen, back, lymph nodes, extremities, vascular, and neurological.  
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings made after the start of treatment that meet the definition of a 
Grade 3 or Grade 4 adverse event must be recorded on the AE CRF. 
6.6 
Clinical Laboratory Evaluations 
Clinical laboratory assessments will be performed by local laboratories as clinically indicated. 
Routine laboratory tests (hematology and clinical chemistry) should be performed at the time 
points designated in the schedule of events for both treatment cohorts (Table 2 and Table 3).  
6.7 
Treatment Perceptions and Health-Related Quality of Life 
Assessments 
The CCSQ will be used to ascertain patients’ perceptions of their chemotherapy regimen in 
terms of its convenience and their overall level of satisfaction. Treatment-related side effects 

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that may impact the patient’s HRQOLwill be evaluated using the FACT-BRM. Patients will 
complete these mandatory assessments at the time points specified in Table 2 and Table 3. 
6.7.1 
CCSQ 
The CCSQ is a questionnaire for oncology patients used to evaluate their overall satisfaction 
with and preferences for chemotherapy. The CCSQ was generated from interviews with 
70 oncology patients, 7 oncologists, 4 nurses, and focus groups of 14 nurses. Interviews took 
place in the US, the United Kingdom, and France and were qualitatively analyzed. The CCSQ 
was designed for adults with a wide range of cancer types and stages and contains 21 items 
and 7 domains: 
1. Expectations of chemotherapy 
2. Feelings about side effects 
3. Oral chemotherapy compliance 
4. Convenience 
5. Satisfaction with chemotherapy 
6. Stopping chemotherapy 
7. Reasons for non-compliance 
6.7.2 
FACT-BRM 
The FACT-BRM is a questionnaire designed to evaluate HRQOLin cancer patients who are 
receiving treatment with biologic response modifiers. The FACT-BRM contains 6 domains: 
1. Physical well-being 
2. Social/family well-being 
3. Emotional well-being 
4. Functional well-being 
5. Additional concerns – Physical 
6. Additional concerns – Mental 
6.8 
Treatment Compliance 
Patients will complete drug administration diaries to track compliance with the recommended 
dosing schedule. These diaries will also capture the onset of AEs in relationship to the day of 
drug administration. The diaries will be returned to the Investigator at the subsequent visit. 
6.9 
Pregnancy 
The occurrence of pregnancy in a female subject or female partner of a male subject will be 
reported and recorded on the CRFs. Pregnancy will be handled as per usual clinical care. If 
interferon therapy is interrupted due to the pregnancy, this should be recorded on the CRFs. 

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7 
Safety Monitoring 
7.1 
Adverse Events 
An adverse event is the appearance or worsening of any undesirable sign, symptom, or 
medical condition occurring after starting the treatment even if the event is not considered to 
be related to the treatment. Treatment includes the investigational drug under evaluation and 
the comparator drug or placebo that is given during any phase of the study. Medical 
conditions/diseases present before starting treatment are only considered AEs if they worsen 
after starting treatment. Abnormal laboratory values or test results constitute AEs only if they 
induce clinical signs or symptoms, are considered clinically significant, or require therapy. 
The occurrence of AEs should be sought by non-directive questioning of the patient at each 
visit during the study. Adverse events also may be detected when they are volunteered by the 
patient during or between visits or through physical examination, laboratory test, or other 
assessments. All Grade 3 or 4 AEs and all SAEs regardless of grade, must be recorded on the 
AE CRF with the following information: 
1. the severity grade (3 or 4 AEs and all SAEs regardless of grade)  
2. its relationship to HDI or PEG IFN therapy (suspected/not suspected) 
3. its duration (start and end dates or if continuing at final exam) 
All adverse events should be treated appropriately. Treatment may include one or more of the 
following: no action taken (ie, further observation only); treatment dosage 
adjusted/temporarily interrupted; treatment permanently discontinued due to this adverse 
event; concomitant medication given; non-drug therapy given; patient hospitalized/patient’s 
hospitalization prolonged. The action taken to treat the adverse event should be recorded on 
the AE CRF.  
Once an adverse event is detected, it should be followed until its resolution or until it is 
judged to be permanent, and assessment should be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the treatment, the 
interventions required to treat it, and the outcome. 
8 
Data Review and Database Management 
8.1 
Site Monitoring 
Before study initiation at any sub-sites, a study representative will review the protocol and 
CRFs with the investigators and their staff, and protocol training will be documented 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, and the results of any other tests or assessments. All information 
on CRFs must be traceable to these source documents in the patient's file. Data not requiring a 
separate written record will be defined before study start and will be recorded directly on the 
CRFs. The investigator must also keep the original informed consent form signed by the 
patient (a signed copy is given to the patient). 

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All multi-site procedures outlined in the multi-site procedures manual must be followed. 
No information in source documents about the identity of the patients will be disclosed. 
8.2 
Data Collection 
Designated investigator staff must enter the information required by the protocol onto the 
paper CRFs, and copies of the interferon preference questionnaire, treatment perceptions, 
HRQOL evaluations and the drug administration diaries will be sent to the coordinating center 
as outlined in the multi-site procedures manual.  
8.3 
Database Management and Quality Control 
Data from the interferon preference questionnaire, treatment perception 
questionnaire,HRQOL evaluations and drug administration diaries will be reviewed by the 
coordinating center staff following their own internal standard operating procedures. 
Errors or omissions on paper CRFs will generate queries that will be returned to the 
investigational site for resolution. Quality control audits will be completed as outlined in the 
multi-site procedures manual, and prior to finalizing data. 
Medical history/current medical conditions and adverse events will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA) terminology. 
9 
Data Analysis 
This is an observational pilot study with no formal sample size calculation based on a 
previously established effect size. For both primary and secondary outcomes, descriptive data 
will be presented (i.e., means and standard deviations or medians and interquartile ranges for 
interval and ordinal data as appropriate; frequencies and percentages for nominal/categorical 
data). Missing data will not be imputed due to the study’s exploratory nature; however, all 
missing data points will be recorded and assessed for possible response patterns. 
Selected inferential analyses will be conducted for exploratory purposes using estimated 
clinically important between-group differences. The study authors will seek to maintain at 
least a 60:40 between-group ratio to guard against unequal variance. 
 
 Primary outcome  
 To compare compliance with HDI and PEG IFN (percentage of doses taken as 
recorded in patient diaries), with a 30% between-group difference deemed clinically 
relevant, a mixed randomized-repeated measures analysis of variance (ANOVA) will 
be conducted with treatment group (HDI versus PEG IFN) as the randomized 
(between-group) factor and treatment period time as the repeated measures (within-
group) factor. For the repeated measures factor of time, given the different induction 
phases for the two regimens (i.e., approximately 4 weeks for HDI versus 8 weeks for 
PEG IFN), the ANOVA will capture outcomes at baseline, 2 weeks, 3 months, 6 

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months and 12 months, with inclusion of the latter outcome dependent on the amount 
of missing data. 
 
 Secondary outcomes: 
 
To compare the convenience and satisfaction with chemotherapy for patients on standard HDI 
versus PEG IFN using a chemotherapy convenience and satisfaction questionnaire (CCSQ), 
with a 30% between-group difference in scores deemed clinically relevant, a mixed 
randomized-repeated measures ANOVA will be conducted for items CS1 – GP5 as a 
summation score, since these items share the same Likert scale anchors and valences. 
Treatment group (HDI versus PEG IFN) will comprise the randomized (between-
group) factor and treatment period time represents the repeated measures (within-
group) factor. For the repeated measures factor of time, given the different induction 
phases for the two regimens (i.e., approximately 4 weeks for HDI versus 8 weeks for 
PEG IFN), the ANOVA will capture outcomes at baseline, 2 weeks, 3 months, 6 
months and 12 months, with inclusion of the latter outcome dependent on the amount 
of missing data. 
 
It should be noted that although the CCSQ is technically an ordinal tool, it will be treated 
as a continuous/interval scale for the purposes of the ANOVA, with transformation of 
outcomes as deemed appropriate. It should also be noted that the CCSQ has not been 
formally validated; therefore, certain items will be presented descriptively, rather than 
inferentially, as per the judgment of the study authors in keeping with the study’s 
exploratory nature. 

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Item GF7, which assesses contentment with current quality of life, will be presented 
descriptively for the two treatment groups as a separate item due to its positively 
worded valence, at baseline, 2 weeks, 3 months, 6 months and 12 months. No 
inferential analyses will be conducted for this item. 
  
For item CS10, which assesses satisfaction with current results of chemotherapy, the 3 
separate “yes” responses will be collapsed for the sake of convenience and presented 
descriptively as a dichotomous outcome for the two treatment groups at 2 weeks, 3 
months, 6 months and 12 months. No inferential analyses will be conducted for this 
item. 
 
Items CS11 and CS12, which measure recommendation/choice of chemotherapy 
regimen, will be presented descriptively for the two treatment groups at 2 weeks, 3 
months, 6 months and 12 months. No inferential analyses will be conducted for these 
items. 
 
Item CS13, which rates the chemotherapy regimen overall, will be presented 
descriptively for the two treatment groups at the end of the study (i.e., 12 months). No 
inferential analyses will be conducted for this item.  
 
 
To evaluate the treatment-related side effects that may impact the patient’s health-related QoL 
(HRQOL) using the Functional Assessment of Cancer Therapy of Biologic Response Modifier 
(FACT-BRM), with a 30% between-group difference in scores deemed clinically relevant, a 
mixed randomized-repeated measures ANOVA will be conducted for all items as a summation 
score, similar to the analysis plan described for CCSQ items CS1 – GP5 (page 23, second 
bullet point). Separate subscales will be presented descriptively for the two treatment groups. 
 
 
The frequency of Grade 3 and 4 toxicities, according to the National Cancer Institute (NCI) 
Common Toxicity Criteria for Adverse Events (CTCAE) for patients on standard HDI versus 
PEG IFN, will be presented descriptively for the two treatment groups at 2 weeks, 3 months, 6 
months and 12 months. No inferential analyses will be conducted for this outcome. 
 
 
Patients’ reasons for their choice of treatment with HDI versus PEG IFN, for those cases in 
which patients are presented with a choice of either treatment option, will be reported 
descriptively at the study’s conclusion (i.e., 12 months). No inferential analyses will be 
conducted for this outcome. 
 
9.1 
Compliance 
Compliance for HDI and PEG IFN will be analyzed by comparing the percentage of doses 
taken (as recorded in the diary) over the treatment period as prescribed by the physician.  

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Analysis of this primary endpoint is described on pages 22-23. 
 
 
9.2 
Safety 
The only adverse events that will be counted will be treatment-emergent Grade 3 and 4 AEs 
and treatment-emergent SAEs regardless of grade. These events are those that started after the 
start of that treatment period, or were present prior to the start of the treatment period but 
increased in severity, or changed from being not suspected to being suspected to be due to 
treatment. 
Treatment-emergent adverse events will be summarized separately for each treatment group 
and by body system and preferred term. Any other information collected (eg, severity or 
relatedness to treatment) will be listed as appropriate. 
Laboratory data will be summarized by presenting summary statistics of raw data and change 
from baseline values (means, medians, standard deviations, ranges) will be provided.  
Data from other tests will be listed, notable values will be flagged, and any other information 
collected will be listed as appropriate. Any statistical tests performed to explore the data will 
be used only to highlight any interesting comparisons that may warrant further consideration. 
9.3 
Sample Size Calculation 
Due to the pilot study design, minimum sample size has not been calculated formally. The 
sample size of 100 patients is expected to generate data adequate to determine if a larger trial 
is warranted. 
9.4 
Interim Analysis 
There is no interim analysis planned for this study. 

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10 
Ethical Considerations 
10.1 
Regulatory and Ethical Compliance 
This clinical study was designed and shall be implemented and reported in accordance with 
the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for 
Good Clinical Practice, with applicable local regulations (including European Directive 
2001/20/EC, US Code of Federal Regulations Title 21, and Japanese Ministry of Health, 
Labor, and Welfare), and with the ethical principles laid down in the Declaration of Helsinki. 
10.2 
Informed Consent Procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/EC -approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative of the patient. 
In cases where the patient’s representative gives consent, the patient should be informed about 
the study to the extent possible given his/her understanding. If the patient is capable of doing 
so, he/she should indicate assent by personally signing and dating the written informed 
consent document or a separate assent form. Informed consent must be obtained before 
conducting any study-specific procedures (ie, all of the procedures described in the protocol). 
The process of obtaining informed consent should be documented in the patient source 
documents.  
St. Luke’s University Health Network (SLUHN) will provide to investigators in a separate 
document a proposed informed consent form that complies with the ICH GCP guideline and 
regulatory requirements and is considered appropriate for this study. Any changes to the 
proposed consent form suggested by the investigator must be agreed to by SLUHN before 
submission to the IRB/EC, and a copy of the approved version must be provided to SLUHN 
after IRB/EC approval. 
Women of childbearing potential should be informed that taking the study medication may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
should not be entered in the study. 
10.3 
Responsibilities of the Investigator and IRB/EC 
The protocol and the proposed informed consent form must be reviewed and approved by a 
properly constituted IRB/EC before study start. A signed and dated statement that the protocol 
and informed consent have been approved by the IRB/EC must be given to SLUHN before 
study initiation. Prior to study start, the investigator is required to sign a protocol signature 
page confirming his/her agreement to conduct the study in accordance with these documents 
and all of the instructions and procedures found in this protocol and to give access to all 
relevant data and records to SLUHN monitors, auditors, Clinical Quality Assurance 
representatives, designated agents of SLUHN, IRBs/ECs, and regulatory authorities as 
required. If an inspection of the clinical site is requested by a regulatory authority, the 
investigator must inform SLUHN immediately that this request has been made. 

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10.4 
Publication of Study Protocol and Results 
SLUHN will ensure that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report the results of this trial will be either submitted for publication 
and/or posted in a publicly accessible database of clinical trial results. 
11 
Protocol Adherence 
Investigators ascertain they will apply due diligence to avoid protocol deviations. All 
significant protocol deviations will be recorded and reported in the CRF. 
11.1 
Protocol Amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by SLUHN and the IRB/EC. Only amendments that are required for patient 
safety may be implemented prior to IRB/EC approval. Notwithstanding the need for approval 
of formal protocol amendments, the investigator is expected to take any immediate action 
required for the safety of any patient included in this study, even if this action represents a 
deviation from the protocol. 

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12 
References 
Eggermont AM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b 
versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised 
phase III trial. Lancet 2008;372:117-26. 
Eggermont AM, Suciu S, Testori A, et al. Long-term results of the randomized phase III trial EORTC 
18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III 
melanoma. J Clin Oncol 2012;30:3810-8. 
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, Altekruse SF, Kosary CL, 
Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA, 
Edwards BK. SEER Cancer Statistics Review, 1975-2008, National Cancer Institute. Bethesda, MD. 
Kilbridge KL, Cole BF, Kirkwood JM, et al. Quality-of-life-adjusted survival analysis of high-dose 
adjuvant interferon alpha-2b for high-risk melanoma patients using intergroup clinical trial data. J Clin 
Oncol 2002;20:1311-8. 
Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b 
adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group 
Trial EST 1684. J Clin Oncol 1996;14:7-17. 
Loquai C, Nashan D, Hensen P, et al. Safety of pegylated interferon-alpha-2a in adjuvant therapy of 
intermediate and high-risk melanomas. Eur J Dermatol 2008;18:29-35. 
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA: A Cancer Journal for Clinicians 
2013;63:11-30. 
Sosman JA. Adjuvant Therapy for Intermediate and High-Risk Melanoma. In: Atkins MB, Ross ME, 
eds. UptoDate. Waltham, MA: , 2013. 

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13 
Appendices 
13.1 
Chemotherapy Convenience and Satisfaction Questionnaire 
(CCSQ) 

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Below is a list of statements that people receiving chemotherapy like yours have said are important. 
For each statement, please choose the reply that best fits your experience with receiving 
chemotherapy, and circle the number corresponding to your reply.  
"Chemotherapy" means the drug(s) you receive to treat your cancer or tumor.  
 
Chemotherapy Experience - 1 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
Much 
CS1 
Chemotherapy treatment takes up my time. 
0 
1 
2 
3 
4 
CS2 
My chemotherapy treatment takes up my 
family’s time. 
0 
1 
2 
3 
4 
CS3 
I worry about side effects from chemotherapy 
treatment. 
0 
1 
2 
3 
4 
CS4 
My chemotherapy treatment causes me physical 
pain. 
0 
1 
2 
3 
4 
CS5 
Receiving chemotherapy is inconvenient. 
0 
1 
2 
3 
4 
CS6 
I worry that my chemotherapy will not be 
effective. 
0 
1 
2 
3 
4 
CS7 
Chemotherapy treatment seems harmful to me. 
0 
1 
2 
3 
4 
CS8 
My chemotherapy schedule is stressful to me. 
0 
1 
2 
3 
4 
CS9 
My chemotherapy schedule is stressful to my 
family. 
0 
1 
2 
3 
4 
GP5 
I am bothered by side effects of treatment. 
0 
1 
2 
3 
4 
 
 
 
 
 
 
 
 
Please answer this last question about how you 
have felt this past week. 
 
 
 
 
 
GF7 
I am content with the quality of my life right 
now. 
0 
1 
2 
3 
4 
 
 
 
 
 
 
Copyright 2002, FACIT, David Cella, Ph.D. 
Version 6, 11-27-02 

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Considering your experience with chemotherapy to date, please respond to the following questions. 
 
Chemotherapy Experience - 2 
No, not at 
all 
Yes, to 
some 
extent 
Yes, for 
the most 
part 
Yes, 
completely 
CS 
10 
Are you satisfied with the current results of 
your chemotherapy? 
0 
1 
2 
3 
 
 
 
No 
Maybe 
Yes 
CS 
11 
Would you recommend this chemotherapy to others 
with your illness? 
0 
1 
2 
CS 
12 
Would you choose this chemotherapy again? 
0 
1 
2 
 
 
 
Poor 
Fair 
Good 
Very 
Good 
Excellent 
CS 
13 
How would you rate this chemotherapy?  
0 
1 
2 
3 
4 
 
Resource Utilization  
A "cycle" of therapy with interferon is defined as one month of treatment and includes the days on 
which you get an infusion or injection or both, and also the days after that until you get another 
infusion or injection. Each month is separate cycle. If you have any question about what period of time 
makes up one “cycle” of treatment, your doctor or nurse can tell you. 
1. How many times did you go to the hospital or doctor’s office for any reason (including scheduled 
visits) during the previous cycle?  
____________ times during the previous cycle to the hospital  
____________ times during the previous cycle to the emergency room or clinic 
____________ times during the previous cycle to the doctor’s office 
 
2. What was the average length of time spent on these visits, including travel to and from, waiting 
time, time with doctor or nurse, drug administration time, and testing/procedure time?  
____________ days during the previous cycle for an average hospital visit  
____________ hours during the previous cycle for an average emergency room or clinic visit  
____________ hours during the previous cycle for an average doctor’s office visit 
 
3. How many total hours did you miss from work and/or your usual activities during your previous 
treatment cycle? 
____________ hours missed during the previous cycle 
 
4. How many total hours have your friends or relatives missed from work and/or their usual activities 
because you needed their help during your previous treatment cycle? 
____________ hours missed during the previous cycle 

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13.2 
FACT-BRM (Version 4) 

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13.3 
Interferon Preference Questionnaire 
 
Study Patient number: ______________ 
Interferon Preference Questionnaire 
1. Did your physician discuss the option of taking standard 
high dose interferon vs. pegylated interferon 
(Sylatron™) with you? 
Yes  □        No  □ 
If you answered “No” to question 1, there is no need to complete the remainder of the 
questionnaire. 
 
2. Please rate the following factors in terms of its  importance with regard to your choice of type of 
interferon therapy: 
a. Frequency of treatment (how often the treatment is 
given) 
Very important                 □            
Somewhat important       □ 
Not important                   □ 
b. Toxicity (side effects) of therapy 
Very important                 □            
Somewhat important       □ 
Not important                   □ 
c. Effectiveness of therapy in preventing or delaying 
return of melanoma 
Very important                 □            
Somewhat important       □ 
Not important                   □ 
d. Convenience of the treatment schedule 
Very important                 □            
Somewhat important       □ 
Not important                   □ 
e. Length of therapy (one year vs. longer) 
Very important                 □            
Somewhat important       □ 
Not important                   □ 
3. Do you perceive that your physician has recommended 
or has a preference between the two treatment options? 
Yes, I followed his/her 
recommendation              □      
Yes, but I chose the other treatment 
option                                  □ 
My physician did not seem to have a 
preference                    □ 
Please add any additional comments here: 
 
 
 
 
 
 

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13.4 
ECOG Performance Scale 
 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature (eg, light house work, office work). 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and 
about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead 
Note: As published in Am. J. Clin. Oncol.: 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response 
Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.