Clinical trial NCT04499950
Conditions: Breast Cancer Overweight or Obesity
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2021-02-08; Completion date: 2024-01-10
Enrollment: 53 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a single arm phase II study designed to determine the effects of pharmacotherapy and a remote behavioral weight loss intervention on weight loss in breast cancer survivors who are overweight or obese, and the impact of successful weight loss on serum biomarkers and gut microbiome.

Detailed description:
The investigators will evaluate the extent to which implementation of a chronic weight loss medication, Contrave® (Naltrexone/Bupropion), is associated with achieving ≥5% weight loss. All patients will receive the POWER-remote behavioral weight loss intervention (BWL) and have a behavioral coach for the duration of the 6 month study. During months 1-3, the behavioral coach will call weekly. From months 4-6, the behavioral coach will call monthly. At week 9, those who lose ≥5%, designated fast responders, will continue with BWL alone (FAST-BWL) while those who lose \<5%, designated slow responders, will continue BWL and initiate Contrave (SLOW-BWL). The SLOW-BWL arm will receive at least 16 weeks of Contrave (as per Federal Drug Administration \[FDA\] recommended administration) starting at week 9 and discontinue if ≥5% weight loss is not achieved at month 6. During month 3, all participants continue to have weekly calls with the behavioral coach and will be asked about symptoms, which may be related to initiation of pharmacotherapy; any symptoms are reported to the PI for further evaluation. In addition to total weight loss, the investigators will evaluate biomarkers associated with obesity, microbiome and cardiometabolic factors.

Arms: arm 1: All patients will receive the POWER-remote behavioral weight loss intervention (BWL) and have a behavioral coach for the duration of the 6 month study. During months 1-3, the behavioral coach will call weekly. From months 4-6, the behavioral coach will call monthly. At week 9, those who lose \<5%, designated slow responders, will continue BWL and initiate Contrave (SLOW-BWL). The SLOW-BWL arm will receive at least 16 weeks of Contrave \[as per the Food and Drug Administration (FDA) recommended administration\] starting at week 9 and discontinue if ≥5% weight loss is not achieved at month 6. arm 2: All patients will receive the POWER-remote behavioral weight loss intervention (BWL) and have a behavioral coach for the duration of the 6 month study. During months 1-3, the behavioral coach will call weekly. From months 4-6, the behavioral coach will call monthly. At week 9, those who lose ≥5%, designated fast responders, will continue with BWL alone (FAST-BWL)
Interventions: intervention 1: Contrave intervention 2: Behavioral Weight Loss
Intervention descriptions: intervention 1: Initiate Contrave at 1 tab in morning (AM) for Week 9; then 1 tab in AM and 1 tab in evening (PM) for Week 10; then 2 tab in AM and 1 tab in PM for Week 11; then 2 tab in AM and 2 tab in PM for week 12; then constant dose for months 4-6. intervention 2: 6 months of behavioral weight loss. First 3 months are weekly calls with coach and then transition to monthly calls for months 4-6.

Protocol documents:
Prot_SAP_000.pdf: 
Adapative Weight Loss for Breast Cancer Survivors Study 
Protocol Chair: Jennifer Sheng, M.D. 
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A PHASE II SINGLE ARM ADAPTIVE WEIGHT LOSS STUDY IN WOMEN WITH 
EARLY STAGE BREAST CANCER 
Protocol Number
 
Protocol Chair 
IRB00223131 
NCT04499950
Jennifer Sheng, MD 
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 
Bunting-Blaustein Cancer Research Building 
1650 Orleans Street, CRB-I 142 
Baltimore, MD 21231-1000 
Phone: 410-614-0762 
Fax: 410-614-4073 
Email: jsheng7@jhmi.edu 
Protocol Co-author 
Co-Investigators: 
Vered Stearns, MD 
Kim Gudzune, MD 
Janelle Coughlin, PhD 
Claire Snyder, PhD 
Date 3/1/2024 


 
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Members of the Breast Cancer Program 
 
Other Collaborators: 
Dipali Sharma, PhD 
 
Biostatistics  
 
Marianna Zahurak, MS  
 
 
 
 
 
 
 
 
 
 
      Supporters 
Breast Cancer Research Foundation 
 
 
 
 
 
 
Research Manager/  
Jeffrey Reynolds 
Study Liaison  
 
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 
 
 
 
 
Phone: 410-614-9869 
Email: jreynolds@jhmi.edu 
 
 
Coordinating Center            Johns Hopkins 
 
 
 
 
Contact: HopkinsBreastTrials@jhmi.edu 
 
 
Protocol Version: 
 
February 12, 2021 
 
 
 
 
May 7, 2021 
 
 
 
 
October 29, 2021 
 
 
 
 
March 2, 2022  
 
 
 
June 13, 2022 
October 11, 2023 
March 1, 2024 
 
 


 
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A PHASE II SINGLE ARM ADAPTIVE WEIGHT LOSS STUDY IN WOMEN WITH 
EARLY STAGE BREAST CANCER 
 
- PROTOCOL REVISION RECORD – 
 
 
Original Protocol: 
 
September 4, 2019 
 
 
 
Version 2 (November 13, 2019)  
Version 3 (February 7, 2020) 
Version 4 (May 13, 2020) 
Version 5 (June 18, 2020) 
Version 6 (August 31, 2020) 
Version 7 (October 27, 2020) 
Version 8 (February 12, 2021) 
Version 9 (May 7, 2021) 
Version 10 (October 29, 2021) 
Version 11 (March 2, 2022) 
Version 12 (June 13, 2022) 
Version 13 (October 11, 2023) 
Version 14 ( March 1, 2024) 
 
 
 


 
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TABLE OF CONTENTS 
- PROTOCOL REVISION RECORD – ....................................................................................................... 3 
1. SUMMARY ............................................................................................................................................. 8 
2. SCHEMA ............................................................................................................................................... 10 
3. HYPOTHESIS....................................................................................................................................... 10 
4. OBJECTIVES ....................................................................................................................................... 10 
4.1 Primary Objectives ............................................................................................................................ 10 
4.2 Secondary Objectives ........................................................................................................................ 10 
5. BACKGROUND AND RATIONALE ................................................................................................ 11 
5.1 The Biology of Obesity and Breast Cancer ...................................................................................... 11 
5.2 Obesity and Breast Cancer Outcomes ............................................................................................... 12 
5.3 Weight Gain in Breast Cancer .......................................................................................................... 12 
5.4 Effects of Obesity on Quality of Life in Breast Cancer .................................................................... 13 
5.5 Predictors of Successful Weight Loss ............................................................................................... 14 
5.6 Weight Loss Interventions for Breast Cancer Survivors ................................................................... 15 
5.7 Biomarkers ........................................................................................................................................ 16 
5.8 Chronic Weight Loss Medications .................................................................................................... 17 
5.9 Efficacy and safety of Contrave® (Naltrexone/Buproprion) ............................................................ 17 
5.10 
Patient Reported Outcomes (PROs) .......................................................................................... 19 
5.11 Summary ......................................................................................................................................... 20 
6. INCLUSION AND EXCLUSION CRITERIA ................................................................................... 20 
6.1 Inclusion criteria ............................................................................................................................... 20 
6.2 Exclusion criteria .............................................................................................................................. 21 
6.3 Inclusion of women and minorities ................................................................................................... 22 
7. STUDY DESIGN AND TREATMENT PLAN................................................................................... 22 
7.1 Recruitment ....................................................................................................................................... 22 
7.2 Determination of Eligibility .............................................................................................................. 23 
7.3 Visits and Follow up ......................................................................................................................... 23 
7.3.1 Screening (by phone call) .......................................................................................................... 24 
7.3.2 Baseline Visit ............................................................................................................................. 25 
7.3.3 Follow-Up Visits ........................................................................................................................ 25 


 
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7.4 Measurements ................................................................................................................................... 26 
7.5 Questionnaires ................................................................................................................................... 27 
7.5.1 Clinical and Demographic Information ..................................................................................... 27 
7.5.2 Patient Reported Outcomes ........................................................................................................ 27 
7.5.3 Nutritional and Physical Activity Assessments ......................................................................... 29 
7.6 BWL intervention ............................................................................................................................. 30 
7.6.1 Goals .......................................................................................................................................... 30 
7.6.5 Participant contact ...................................................................................................................... 31 
7.6.6 Assessment of adherence ........................................................................................................... 31 
7.6.7 Provider role ............................................................................................................................... 31 
7.6.8 Description of BWL Intervention .............................................................................................. 31 
7.6.9 Weight Goals and Behavioral Recommendations ...................................................................... 32 
7.7. Concomitant and Supportive Therapy ............................................................................................. 32 
7.8 Discontinuation and withdrawal of subjects ..................................................................................... 33 
7.11 Discontinuation of intervention ...................................................................................................... 33 
7.12 Withdrawal from Study ................................................................................................................... 33 
7.13 Additional Information ................................................................................................................... 33 
9. CORRELATIVE STUDIES ................................................................................................................. 35 
9.1 Blood Samples .................................................................................................................................. 35 
9.1.1 Collection ................................................................................................................................... 35 
9.1.2 Analysis ...................................................................................................................................... 36 
9.2 Fecal Samples ................................................................................................................................... 36 
9.3 Leftover Samples .............................................................................................................................. 36 
9.4 Additional information ...................................................................................................................... 36 
10. ADVERSE EVENTS .......................................................................................................................... 36 
10.1 
General ...................................................................................................................................... 36 
10.2 Potential Risk from Intervention ..................................................................................................... 37 
10.2.1 Physical Activity ...................................................................................................................... 37 
10.2.2 Nutrient Intake ......................................................................................................................... 37 
10.2.3 Hypoglycemia .......................................................................................................................... 37 
10.2.4 Symptomatic Hypotension ....................................................................................................... 38 


 
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10.2.5 Cardiovascular Events .............................................................................................................. 38 
10.2.6 Symptoms Related to Contrave ................................................................................................ 38 
10.2.6 Survey fatigue .......................................................................................................................... 38 
10.3 Definitions....................................................................................................................................... 38 
10.4 Relationship .................................................................................................................................... 39 
10.5 Reporting Procedures ...................................................................................................................... 40 
10.5.1 General ..................................................................................................................................... 40 
10.5.2 Serious Adverse Events ........................................................................................................... 40 
10.5.3 Institutional Review Board (IRB) ............................................................................................ 40 
11. DATA AND SAFETY MONITORING ............................................................................................ 41 
11.1 Data management ............................................................................................................................ 41 
11.2 Meetings .......................................................................................................................................... 41 
11.3 Monitoring ...................................................................................................................................... 42 
11.4 Data Safety Monitoring Board ........................................................................................................ 42 
12. ADMINISTRATIVE PROCEDURES .............................................................................................. 42 
12.1 Protocol Amendments ..................................................................................................................... 43 
12.2 Informed Consent ............................................................................................................................ 43 
12.3 Ethics and Good Clinical Practice .................................................................................................. 43 
12.4 Regulatory Authorities .................................................................................................................... 43 
13. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ................................................... 44 
13.1 Study Design ................................................................................................................................... 44 
13.2 Analysis Plans ................................................................................................................................. 45 
13.3 Early Stopping ................................................................................................................................ 46 
REFERENCES .......................................................................................................................................... 47 
APPENDICES ........................................................................................................................................... 57 
APPENDIX A:  ECOG Performance Status Scale ................................................................................. 58 
APPENDIX B:  Lifestyle Guidelines Handout ....................................................................................... 59 
APPENDIX C:  Weekly weight and symptom survey............................................................................ 61 
APPENDIX D: Aim for a Healthy Weight Brochure ............................................................................. 62 
APPENDIX E:  PRO Questionnaire ....................................................................................................... 63 
APPENDIX F: Score Interpretation ........................................................................................................ 83 


 
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APPENDIX G:  Drug Diary ................................................................................................................... 85 
 
 
 


 
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1. SUMMARY 
Excess body weight is a significant risk factor for many cancers, especially breast cancer. 
Obesity can affect survivorship and quality-of-life factors including sexual function, neuropathy, 
cardiotoxicity, chronic fatigue and lymphedema. In retrospective studies, patients with a history 
of or current breast cancer who are overweight or obese are at an increased risk of therapy-
related morbidity, recurrence, and breast cancer-related mortality1,2. Most cancer guidelines 
recommend that breast cancer survivors who are overweight or obese lose weight and that those 
within a normal body mass index (BMI) maintain a stable body weight. The cornerstone of 
interventions to treat or prevent obesity includes lifestyle modification with diet and exercise; 
however, integration into clinical practice is challenging due to limitations with standardization 
and scalability.  
Our collaborators from the Welch Center for Prevention, Epidemiology, and Clinical Research at 
the Johns Hopkins University have reported impressive and sustained weight loss in randomized 
controlled trials designated Practice-based Opportunities for Weight Reduction (POWER) in 
obese women with at least one cardiovascular risk factor using a remote-support weight loss 
intervention3. This remote-support weight loss intervention of the POWER study has been 
adapted in women with early breast cancer who are overweight or obese, designated POWER-
remote, and demonstrated statistically significant weight loss of ≥5% body weight, compared to 
self-directed weight loss at 6 and 12 months4.  Our recent evaluation of 6 months of the POWER 
intervention in breast cancer survivors found that 46% of women randomized to the POWER-
remote arm were able to lose ≥5% of their baseline weight as compared to only 10.9% of women 
in the self-directed arm.  
While some patients with early stage breast cancer are able to achieve significant clinically 
meaningful loss, the majority are unable to. The goal of this project is to evaluate whether weight 
loss in overweight/obese breast cancer survivors whose trajectory suggests unlikelihood of 
attaining clinically significant weight loss of ≥5% with behavioral intervention alone can be 
augmented with pharmacotherapy. Studies have shown that self-directed weight loss is generally 
not successful. Our POWER-remote study showed that 89.1% of women in the self-directed arm 
were not successful in weight loss. With the implementation of remote behavioral intervention, 
this value drops to 54% of women not being able to lose at least 5% of their weight. We will 
focus on this population of women, as they may be identified earlier (after 4-12 weeks of 
behavioral intervention). Success for this study will be measured by the rate of these women who 
are able to achieve weight loss with the adapted behavioral intervention with pharmacotherapy. 
As there are over 3 million breast cancer survivors in the US5, many of whom are 
overweight/obese, underutilization of anti-obesity drugs may be a critical and neglected 
component of weight loss treatment.  
We will evaluate the extent to which implementation of a chronic weight loss medication, 
Contrave® (Naltrexone/Bupropion), is associated with achieving ≥5% weight loss. All patients 
will receive the POWER-remote behavioral weight loss intervention (BWL) and have a 
behavioral coach for the duration of the 6 month study. During months 1-3, the behavioral coach 
will call weekly. From months 4-6, the behavioral coach will call monthly. At week 9, those who 
lose ≥5%, designated fast responders, will continue with BWL alone (FAST-BWL) while those 


 
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who lose <5%, designated slow responders, will continue BWL and initiate Contrave (SLOW-
BWL). The SLOW-BWL arm will receive at least 16 weeks of Contrave (as per Federal Drug 
Administration [FDA] recommended administration) starting at week 9 and discontinue if ≥5% 
weight loss is not achieved at month 6. During month 3, all participants continue to have weekly 
calls with the behavioral coach and will be asked about symptoms, which may be related to 
initiation of pharmacotherapy; any symptoms are reported to the Protocol Chair for further 
evaluation. In addition to total weight loss, we will evaluate biomarkers associated with obesity, 
microbiome and cardiometabolic factors.   
The ability of a diet and behavioral interventions to promote a more favorable microbiome 
profile, a lower BMI, and reduced levels of inflammatory cytokines, may help explain why 
vegetarian diets, and particularly vegan diets, seem to be protective against cancer growth in 
general and PC in particular.  Our study, through its focus on inflammatory biomarkers, analysis 
of fecal microbiota, and traditional metabolic endpoints such as weight loss, adiposity, insulin 
resistance and hyperlipidemia, will help elucidate the complex interplay between metabolic 
disorders and inflammation in breast cancer survivors.  Perhaps more importantly, we are 
confident that our study will offer breast cancer survivors a low-risk strategy to weight 
management, with tremendous potential for near-term impact on their quality of life and health 
outcomes. We will also assess certain genotypes to determine whether the effect of an adaptive 
weight loss intervention on biomarkers is greater in the patients who have a particular genotype 
(e.g. AA-SOD2). The potential increase in antioxidants in the adaptive weight loss intervention 
may enable certain patients with certain genotypes to gain greater benefit from the diet than 
others. 
Our research will address a major gap in the literature that could potentially improve quality of 
life and cancer and non-cancer outcomes for obese breast cancer patients. While many studies 
have explored various interventions for weight loss in cancer survivors, to our knowledge none 
have explored the influence of weight loss pharmacotherapy in breast cancer survivors. 
Additionally, these medications have not been studied in the setting of use of hormonal therapy, 
such as tamoxifen or an aromatase inhibitor. The data will be used not only to assess the impact 
of weight loss and biomarker modulation but also to design definitive studies available to all 
overweight and obese women with breast cancer whom struggle to achieve clinically significant 
weight loss despite lifestyle intervention.  
 


 
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2. SCHEMA 
 
3. HYPOTHESIS 
 In SLOW-BWL, adding Contrave at week 9 of a weight loss intervention may augment 
BWL and allow women to lose ≥5% of their baseline body weight at 6 months.  
 In SLOW-BWL, weight loss of ≥5% baseline body weight will be associated with 
changes in the following from baseline to 2 and 6 months:  
o reductions in fasting glucose, fasting insulin, total and low-density lipoprotein 
(LDL) cholesterol, triglycerides, leptin;  
o increases in high-density lipoprotein (HDL) cholesterol and adiponectin;  
o altered gut microbiome (decrease in the ratio of bacteroides and firmacutes); and 
o improved patient reported outcomes (PROs) 
o increased total lean mass, and decreased % fat mass and visceral fat 
 Compared to women who are able to achieve at least 5% weight loss with 2 months of 
behavioral intervention alone, women who are unable to achieve ≥5% weight loss with 
behavioral intervention alone may have identifiable baseline characteristics (i.e., 
cardiometabolic profile, obesity biomarker, microbiome composition or PROs) that may 
be predictors of whom may benefit from earlier initiation of pharmacotherapy.  
4. OBJECTIVES 
4.1 Primary Objectives 
4.1.1 To assess the rate of SLOW-BWL patients attaining at least 5% weight loss of their 
baseline body weight at 6 months with the addition of Contrave to BWL at week 9.  
4.2 Secondary Objectives   


 
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4.2.1 To compare cardiometabolic biomarkers (HbA1c, IGF 1, fasting glucose, fasting lipids, 
fasting insulin, adiponectin and leptin levels), microbiome composition, body composition, and 
PROs at 2 and 6 months to baseline levels among SLOW-BWL who achieve ≥5% weight loss. 
4.2.2 To compare cardiometabolic biomarkers, microbiome composition, body composition, and 
PROs at baseline of SLOW-BWL women who achieve ≥5% weight loss versus the SLOW-
BWL women who do not achieve 5% weight loss.  
4.2.3 To compare the moderate to vigorous physical activity (MVPA) and daily steps at 2 and 6 
months to baseline levels among SLOW-BWL who achieved ≥5% weight loss vs the SLOW-
BWL who did not achieve 5% weight loss. 
4.3 Exploratory  
4.3.1 To assess the proportion of women in the FAST-BWL arm who maintain ≥5% weight loss 
at 6 months.  
4.3.2 To describe baseline characteristics (cardiometabolic and obesity biomarkers, microbiome 
composition, PROs, demographics) of FAST-BWL vs SLOW-BWL, as well as participants who 
achieve ≥5% weight loss at 6 months vs those who are unable to. 
4.3.3 To assess prevalence of AA genotype of MnSOD in breast cancer survivors with excess 
weight and if a greater proportion of women with the AA genotype achieve ≥5% weight loss 
and improvement in biomarkers at 6 months compared to the women who do not.  
4.3.4 To determine if women who display the AA genotype of MnSOD and undergo addition of 
Contrave to BWL have greater weight loss compared to women who do not receive Contrave. 
 
 
5. BACKGROUND AND RATIONALE 
5.1 The Biology of Obesity and Breast Cancer 
Studies have strongly suggested that excess body weight and weight gain may be a major risk 
factor for many cancers including breast cancer6–8.  The biological relationship between obesity 
and breast oncogenesis is mediated by several pathways. Obesity has been associated with 
increased levels of inflammatory cytokines, for example interleukin 1β, interleukin 6, tumor 
necrosis factor α, and monocyte chemoattractant protein 1. Altered levels of these cytokines 
drive pro-proliferative pathways, such as angiogenesis, influx of macrophages, and anti-
apoptotic pathways 9. Another untoward effect of obesity is increased synthesis of estrogens 
from androgens via augmented aromatization of androstenedione in peripheral adipose tissue.  
Breast carcinogenesis has also been associated with increased serum leptin levels and low 
adiponectin. Leptin is an adipocytokine synthesized by adipocytes and it acts as a satiety 
hormone at the hypothalamus level to reduce appetite and is paradoxically elevated in obese 
individuals 10. High levels of leptin lead to concomitant activation of various oncogenic 
pathways resulting in increased tumor growth, angiogenesis and acquisition of a migratory and 


 
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invasive mesenchymal phenotype 11. Adiponectin counters obesity by modulating glucose 
metabolism, increasing fatty acid oxidation and insulin sensitivity, and decreasing production of 
inflammatory cytokines.  
Increased adiposity also increases circulating levels of insulin and insulin-like growth factor 1, 
which may also promote cell proliferation. Favorable changes in estrogens, sex hormone binding 
globulin, insulin, and leptin are observed in association with weight loss of at least 5% 12. 
Furthermore, weight loss of at least 10% has been associated with modulation of serum and 
tissue biomarkers, such as Ki-67, adiponectin, adiponectin to leptin ratio, sex hormone binding 
globulin, estradiol, testosterone and insulin13. These biological data not only provide insight into 
how obesity can increase the risk of breast cancer, but suggests that weight loss may reverse 
some of these deleterious biological changes associated with obesity.  
5.2 Obesity and Breast Cancer Outcomes 
The four major cancer agencies (International Agency for Research on Cancer [IARC], 
American Cancer Society [ACS], American Institute for Cancer Research [AICR], and Center 
for Disease Control [CDC]) recommend that survivors maintain a stable body weight in the 
normal range and avoid weight gain14. Retrospective studies have shown that patients with breast 
cancer who are obese have an increased relative risk of recurrence by 40-50% and breast cancer-
related mortality by 53-60% 1,2. Obese women with hormone receptor positive operable breast 
cancer have inferior outcomes in terms of disease free survival (DFS) (Hazards Ratio [HR], 1.24; 
95% confidence interval [CI], 1.06-1.46; P = 0.0008) and overall survival (OS) (HR, 1.37; 95% 
CI, 1.13-1.67; P = 0.002) in comparison to non-obese group 15. Overall, approximately 15% of 
breast cancer cases in postmenopausal breast cancer survivors may be attributable to weight gain 
16. In premenopausal women, short-term weight gain may increase breast cancer risk although 
data are mixed 17.  
In the Women’s Intervention Nutrition Study (WINS), women with early stage breast cancer on 
a dietary intervention with clinically meaningful weight loss had 24% lower risk of relapse 
compared to those not receiving the intervention18. In the Women’s Healthy Eating and Living 
(WHEL) study, dietary intervention did not lead to weight loss and did not reduce breast cancer 
recurrence19. These studies suggest that alteration in diet or activity alone may not be sufficient, 
and that greater loss is required to improve breast cancer-related outcomes20. While definitive 
data are pending, initial data suggest that weight management for improved cancer related 
outcomes is an important aspect of survivorship care.  
To confirm the positive impact of weight loss on survival outcomes (such as DFS), a large 
randomized study has been designed and is actively accruing 21. The Alliance for Clinical Trials 
in Oncology Breast Cancer Weight Loss trial (BWEL, NCT02750826) is testing the 10 year 
impact of a telephone weight loss program on invasive DFS in 3136 women with a BMI 
≥27 kg/m2 with recent diagnosis of stage II-III estrogen receptor positive or triple negative breast 
cancer 22.  
5.3 Weight Gain in Breast Cancer  
Chemotherapy associated weight gain is experienced by most patients during their first year of 
diagnosis 23. There is greater weight gain among postmenopausal women receiving 


 
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chemotherapy than women receiving just surgery or surgery plus radiation, but not among 
premenopausal women or women who became postmenopausal after diagnosis. Studies have 
shown that women have decreased levels of physical activity after the diagnosis of breast cancer, 
which may contribute in part to weight gain. Moreover adjuvant chemotherapy may also 
decrease resting rates of metabolism 24. Additionally, hormonal changes during menopause can 
affect metabolism and lead to weight gain1,2.  
Large studies have not demonstrated an association between hormone therapy and weight gain. 
In the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, comparing anastrozole and 
tamoxifen, there was no significant difference in weight gain between the two therapies (median 
weight gain 1.4 kg (SD 3.9) versus 1.5 kg (SD 4.0), respectively P = 0.4)25. Recent data, from the 
Exercise and Nutrition to Enhance Good Health for You (ENERGY) trial, however, suggests that 
patients receiving an AI may be less likely to gain weight than those on a selective estrogen 
receptor modulator (OR = 0.54, 95 % CI 0.31–0.93)26. While these data may be conflicting, and 
there are numerous other variables such as chemotherapy and menopausal status that can affect 
weight gain, there is insufficient evidence to suggest endocrine agents in general cause a 
significant amount of weight gain, and efforts at weight management should be directed at 
lifestyle changes rather than therapy discontinuation.  
5.4 Effects of Obesity on Quality of Life in Breast Cancer 
Obesity at and following breast cancer diagnosis is significantly associated with poor health-
related quality of life and functional health, and may increase the risk of adverse treatment 
effects.  
Obesity can affect body image, sexual and genitourinary function in breast cancer survivors. A 
cross-sectional survey of 255 patients at least one year from surgery showed that obese and 
overweight women reported more appearance dissatisfaction (18.1 and 13.0%) than normal 
weight women (4.1%) (p=0.02). A greater proportion of overweight women (94.7%) reported 
their chest played an important role in intimacy before and after surgery as compared to normal 
weight women (80.6%), but a postoperative decline in the importance of this role was observed 
in all groups (overweight p=0.01, normal weight p<0.001) 27. Furthermore, being overweight or 
obese at baseline was associated with more problems with urinary incontinence and tendency to 
nap, and with poorer physical functioning and bodily pain (versus BMI<25 kg/m2) 28.  
Neuropathy is more common in patients who are obese. Chemotherapy-induced 
peripheral neuropathy (CIPN) has been reported in up to 44% of patients receiving 
chemotherapy, particularly taxanes 29. Higher BMI is associated with a higher incidence of 
neuropathy, with studies demonstrating a prevalence of 48.4% in participants with normal 
weight, 60.2% in overweight participants, and 66.7% in obese participants. Compared with 
women of normal weight, being obese was associated with an increased risk of CIPN (adjusted 
OR 1.94, 95 % CI: 1.03-3.65) 30.  Increased neuropathy was significantly more likely to occur in 
overweight compared with normal weight patients receiving taxane treatment at 24 months and 
less likely to occur in patients with high moderate-to-vigorous physical activity compared with 
those with lower activity at 24 months 31. While studies have not shown that weight loss can 
reverse neuropathy, these data suggest that physical activity may help decrease neuropathy.  


 
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Because obesity is already a strong risk factor for cardiovascular disease, cancer treatment in 
obese patients can further increase overall risk for adverse cardiac effects 32. A recent meta-
analysis suggests that being overweight or obese may be risk factors for cardiotoxicity from 
anthracyclines, especially in sequence with trastuzumab 33. Other studies have found obesity to 
be associated with an increased risk of cardiac dysfunction in women using trastuzumab 34. 
Additionally, in elderly patients (over 65 years), obesity is an independent risk factor for 
trastuzumab-related cardiac toxicity 35. 
About one third of breast cancer survivors have chronic fatigue and about one fourth will have 
persistent fatigue after two years 36. Although the development of fatigue in breast 
cancer patients seems largely impacted by cancer therapy, the long-term persistence of fatigue is 
related to preexisting medical conditions and lifestyle factors. Higher BMI at baseline is 
significantly associated with increased physical fatigue during and after cancer treatment 37. The 
Mammary carcinoma Risk factor Investigation (MARIE) study demonstrated that both 
physically inactive lifestyle and obesity were associated with persistent physical fatigue, 
independent of chemotherapy and radiation 38. In a study of patients who were overweight or 
obese, fatigue after chemotherapy lower in an exercise group versus a non-exercise group 39. 
Higher BMI, associated with greater tendencies to catastrophize about fatigue and amplify 
physical symptoms, was predictive of fatigue at beyond nine months 40.  These studies 
demonstrate the importance of an ideal body weight as chronic fatigue is associated with 
emotional distress and limits function and willingness to exercise. 
Lymphedema is more common in obese patients. Cancer treatments such as lymph node 
dissection and radiotherapy can damage the lymphatic drainage routes, leading to fluid build-up, 
discomfort, and reduced mobility and function. Excess adiposity may increase risk of 
lymphedema by increased inflammation, added stress to the lymphatic system, or slower healing 
times after surgery 41. Data suggests that obesity increases risk of lymphedema after treatment 
for breast cancer. Prospective studies have reported statistically significantly higher lymphedema 
risk for obese compared to normal-weight women (OR 2.48; 95% CI 1.05–5.84) 42. Breast 
cancer survivors who were obese at the time of breast cancer treatment were approximately 3.6 
times more likely to develop lymphedema at 6 months after diagnosis than those who were not 
obese 43. In a pilot study among overweight breast cancer survivors, a 12 week diet intervention 
resulted in a significant reduction in BMI and swollen arm volume (reduced from 24% to 15%, 
p=0.02) 44.   
5.5 Predictors of Successful Weight Loss 
Initial weight loss response at 4-12 weeks predicts weight loss at 1 year and afterward45–48. In the 
Look AHEAD trial, individuals with diabetes who lost 5% of initial weight at 2 months were 7.9 
times more likely to achieve 10% weight loss at 12 months than those whom could not achieve 
5% weight loss at 2 months47. At one year, the arm with intensive lifestyle intervention lost 8.6% 
of initial weight and the support arm lost 0.7%. Of 2,303 patients, over 55% were slow 
responders (unable to lose >5% of initial weight at 2 months) and only 18.5% of patients in this 
group were able to achieve 10% weight loss at 12 months. Of those whom were fast responders 
(losing >5% initial weight at 2 months), 63.8% succeeded in losing 10% weight at 12 months.  


 
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Interestingly, weight loss of ≥10% has been associated with greater improvement in physical 
function as measured by physical performance test and functional status questionairre49. A 
substudy of women in this trial demonstrates that women tend to lose less weight than men at 
one year in the intensive lifestyle intervention group versus the diabetes support and education 
group50. Unfortunately, many patients are unable to achieve clinically significant weight loss of 
≥5% and regardless of initial weight loss success, sustaining long term weight loss is 
difficult51,52. Thus, new interventions that will allow all individuals to achieve optimal and 
sustained weight loss are urgently needed.  
 
5.6 Weight Loss Interventions for Breast Cancer Survivors 
Table 1. Studies of Remotely Supported Weight Loss Interventions with ≥ 100 Participants with 
Early-Stage Breast Cancer who were Overweight/Obese 
Study  
Breast Cancer 
Subtype 
Intervention Arms  
(Duration) 
Mean Weight 
Changes* 
Lifestyle Intervention in Adjuvant 
Treatment of Early Breast Cancer 
(LISA)53, 2014
HR+, 98%–99% 
HER2+, 8%–
14% 
1. Remote  
2. Mailed information 
(24 mo)
1. −3.1 kg  
2. −0.3 kg 
Exercise and Nutrition to Enhance 
Recovery and Good Health for 
You (ENERGY) study54, 2015
NR 
 
1. Remote (w/group program) 
2. Usual care 
(24 mo)
1. −3.7% 
2. −1.3%  
Sex Hormones and Physical 
Exercise (SHAPE-2) study55, 2015 
NR 
1. Mainly calorie restriction 
2. Mainly exercise 
3. Usual care 
(4 mo)
1. −4.95 kg  
2. −5.58 kg  
3. +0.06 kg 
Christifano et al56, 2016 
NR 
Single arm, Remote 
(6 mo)
−13.2%  
Fazzino et a57, 2017 
HR+, 73%  
Single arm, Remote (w/Fitbit) 
(6 mo)
−13.9%  
Hormones and Physical Exercise 
(HOPE) study58, 2017 
All HR+ 
 
1. Supervised  
2. Remote 
(12 months) 
1. BMI, −0.73 
kg/m2  
2. BMI, −0.17 
kg/m2
Dieli-Conwright et al59, 2018 
HR+, 84%  
1. Supervised 
2. Usual care (w/Fitbit) 
(4 mo)
1. −4 kg  
2. +0.5 kg 
*All values are statistically significant. 
BMI = body mass index; HER2 = human epidermal growth factor receptor; HR = hormone 
receptor; NR = not reported. 
Studies of overweight and obese patients in a primary care setting shows that intensive, face-to-
face behavioral counseling for at least 3 months with at least 6 months follow up can induce 
clinically meaningful weight loss 60. Since limitations of in-person weight loss interventions are 
constraints in time and cost, remote interventions with similar efficacy are more scalable with 
real-world integration.  


 
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At Johns Hopkins, the POWER trial in obese individuals with at least one cardiovascular risk 
factor (n=415) demonstrated equivalent weight loss outcomes between in person coaching and a 
remote-support weight loss intervention (telephone calls by a health coach, Fitbits to assess 
physical activity, self-directed dietary and activity monitoring, and web-based learning modules) 
3. Participants were recruited from six primary care practices in Baltimore, Maryland and 63.6% 
were women and the mean age was 54.0 years. One intervention provided patients with weight-
loss support remotely through the telephone, a study-specific Web site, and e-mail. The other 
intervention provided in-person support during group and individual sessions, along with the 
three remote means of support. There was also a control group in which weight loss was self-
directed. In these two behavioral interventions, one delivered with in-person support and the 
other delivered remotely without face-to-face contact between participants and coaches, obese 
patients achieved and sustained clinically significant weight loss over a period of 24 months. At 
6 months, 52% of participants in the intervention group and 14% of participants in the control 
group achieved ≥5% weight loss.  
An adaption of this remote intervention was implemented in a study of overweight or obese 
breast cancer survivors in a phase II single-blind trial from 2013-2015, which aimed to compare 
a remotely-delivered weight loss intervention (POWER-remote) to self-directed weight loss. At 6 
months, 46% of women randomized to the POWER-remote arm were able to lose ≥5% of their 
baseline weight as compared to only 10.9% of women in the self-directed arm4. At 12 months, 
38% of patients were able to achieve 5% weight loss with the intervention versus 13% in the 
self-directed arm. Weight loss correlated with significant decreases in leptin, and favorable 
modulation of inflammatory cytokines and lipid profiles.  
The POWER-remote is a feasible and scalable behavioral weight loss intervention. While almost 
half of patients were able to achieve ≥5% weight loss at 6 months with behavior intervention, 
only half of these women were able to maintain this at 12 months. Given evidence in the obese 
population about earlier predictors of sustainable weight loss, we plan to identify women who 
are “SLOW” responders to POWER-remote (unable to achieve at least 5% weight loss at 2 
months) and to implement pharmacotherapy to augment lifestyle modifications. We hope to 
discover novel strategies to help breast cancer survivors treat obesity and to potentially improve 
non-cancer and cancer outcomes.  
5.7 Biomarkers and Genes 
Prior studies have demonstrated that weight loss is associated with decreased all-cause 
mortality61, decreased prevalence of prediabetes and cardiovascular disease62, decreased 
glycemic parameters, decreased fasting lipids and decreased biomarkers such as adiponectin, 
insulin, IGF-1, leptin4,59. Weight loss studies have also demonstrated alteration in the gut 
microbiome which may be mediated by epigenetic modulation of gene activity in cancer63.  
Oxidative damage has been implicated in the pathogenesis of many chronic progressive diseases, 
such as cancer and obesity.64–67 Mn superoxide dismutase (MnSOD) is the main enzyme 
responsible for scavenging reactive oxygen species (ROS) in mitochondrial oxidative stress, and 
catalyzing the dismutation of the superoxide radical (O2−) to H2O2.68,69 There are three known 
forms of SOD: (a) the cytosolic copper/zinc SOD; (b) the extracellular copper/zinc SOD; and (c) 


 
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the mitochondrial MnSOD.70 MnSOD is synthesized in the cytosol and posttranscriptionally 
modified for transport into the mitochondrion. In mice,  MnSOD deletion in adipocytes is 
protective against weight gain and insulin resistance through the stimulation of mitochondrial 
function and biogenesis, thereby allowing the clearance of fatty acids.71 However, other studies 
suggest a positive association between MnSOD polymorphism and obesity.72   
Low MnSOD activity, depending on SOD2 genetic polymorphisms, may contribute to the breast 
carcinogenesis and survival.35,73,74 The most commonly studied polymorphism of the SOD2 gene 
is a single nucleotide substitution of C to T at the second nucleotide of codon 16 of 
the SOD2 gene, encoding an amino acid substitution from alanine to valine at position 9 of the 
mitochondrial targeting sequence of the mature protein. MnSOD genotypes containing the 
variant A allele were found to be associated with a 1.5 fold increased risk of breast cancer 
compared with the homozygous wildtype genotype.75 In fact, increased expression 
of MnSOD has been found to suppress the malignant phenotype of human breast cancer cells 
suggesting that MnSOD is a tumour suppressor gene in human breast cancer.76 However, some 
studies show that a MnSOD variant allele appears to be associated with an improved recurrence-
free survival in breast cancer patients.77  
Levels of oxidative damage vary with the consumption of meats, vegetables, and fruits.78 Risk of 
breast cancer was greatest among women who consumed lower amounts of dietary antioxidants 
and was minimal among high consumers indicates that a diet rich in sources of antioxidants may 
minimize the deleterious effects of the MnSOD polymorphism.79,80  
5.8 Chronic Weight Loss Medications 
A domain that may offer enhanced behavioral approaches to weight loss includes 
pharmacotherapy81. Anti-obesity drugs, via reduction of hunger and food cravings and 
enhancement of satiety, help patients to limit the amount of food they eat, thereby increasing 
their adherence to the prescribed diet plan81. Based on data demonstrating weight loss of 5% 
difference between active treatment and placebo, the FDA has approved 5 drugs for long term 
use (greater than 12 weeks) as an adjunct to lifestyle for chronic weight management in 
individuals with BMI ≥ 30.0 kg/m2 or BMI of 27.0-29.9 kg/m2 with co-morbidities such as 
hypertension, diabetes, or dyslipidemia82,83. Although nearly half of obese patients meet BMI 
eligibility criteria for anti-obesity drugs, it is estimated that ≤3.5% receive prescriptions for these 
drugs in the US84. Barriers to the initiation or sustained use of obesity medications include lack 
of insurance coverage, safety concerns, perception of limited efficacy, and reluctance to view 
obesity as a disease requiring treatment84–87.  
5.9 Efficacy and safety of Contrave® (Naltrexone/Buproprion)  
The most recent practice guidelines for medical care of patients with obesity by the American 
Association of Clinical Endocrinologists (AACE) Board of Directors and the American College 
of Endocrinology (ACE) Board of Trustees report that the addition of pharmacotherapy produces 
greater weight loss and weight loss maintenance compared with lifestyle therapy alone and that 
short term treatment (3-6 months) using weight loss medications has not been demonstrated to 


 
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produce longer-term health benefits and cannot be generally recommended based on scientific 
evidence. In selecting the optimal weight loss medication for each patient, clinicians should 
consider differences in efficacy, side effects, cautions and warning that characterize medications 
approved for chronic management of obesity88. FDA-approved monotherapy options include 
phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). 
However, monotherapies have limited efficacy, in part due to the recruitment of alternate and 
counter-regulatory pathways.  
Consequently, a multi-target approach may provide greater benefit89. Combination products 
approved by the FDA to treat obesity include phentermine/topiramate (Qsymia®) and 
naltrexone/bupropion (Contrave®). Although the weight loss produced by 
phentermine/topiramate is superior to naltrexone/bupropion, the safety profile of 
naltrexone/bupropion has less severe adverse effects. In addition, naltrexone/bupropion is well 
tolerated, with nausea being the most reported adverse event. Unlike other centrally acting 
medications, lorcaserin and phentermine/topiramate, naltrexone/bupropion has no abuse 
potential90. 
Approved by the FDA in September 2014, Contrave is an oral, sustained-release combination of 
the dopamine and norepinephrine reuptake antagonist bupropion and the opioid antagonist 
naltrexone. The proposed mechanism of action of the compound involves complementary 
stimulation of central melanocortin pathways, resulting in increased energy expenditure and 
reduced appetite91. Effects may result from action on areas of the brain involved in the regulation 
of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine 
circuit (reward system).  
The safety and efficacy of Contrave were assessed in four randomized, double-blind, placebo-
controlled, 56-week Phase III clinical trials in 4536 adult subjects: COR-1, COR-II, COR-
BMOD and COR-DM. All four studies demonstrated statistically significant and clinically 
meaningful weight loss following up to 52 weeks of treatment compared with placebo92. Mean 
total weight loss across studies for Contrave was 6.8% (95% CI, 6.6-7.1%) or 7.3 kg (95% CI, 
7.0-7.6 kg) at 1 year, ranging from 5.0% (5.4 kg) in patients with diabetes receiving minimal 
behavioral intervention to 9.3% (9.7 kg) in those receiving intensive behavioral treatment93. In 
all studies, significantly more participants taking Contrave achieved weight loss of at least 5% at 
1 year than placebo, ranging from 44.5% (vs 18.9%) in patients with type 2 diabetes receiving 
minimal behavioral treatment to 66.4% (vs 42.5%) in patients without diabetes undergoing 
intensive behavioral treatment. 
Additionally, across the four phase 3 studies, treatment with NB32 resulted in statistically 
significant and clinically meaningful improvements on multiple weight-related cardiometabolic 
parameters, such as fasting triglyceride levels, fasting HDL, high sensitivity C-reactive protein 
(CRP), glycemic control in patients with diabetes and fasting glucose/insulin/ Homeostatic 
Model Assessment for Insulin Resistance (HOMA-IR) in nondiabetics. Furthermore, improved 
quality of life was associated with weight reduction and was achieved in more subjects treated 
with Contrave than placebo94. Weight loss was associated with significant improvement in the 
Impact of Weight on Quality of Life questionnaire-Lite (IWQOL-Lite) score compared with 


 
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placebo (NB-301, NB-302, and NB-303). There were improvements (p<0.05) in Contrave-
treated patients compared with placebo-treated in the following subscales: 
• Physical function (all four Phase 3 studies); 
• Self-esteem (NB-301, NB-302, and NB-303); 
• Sexual life (NB-301 and NB-303); 
• Public distress (NB-301 and NB-303); and 
• Work (NB-301). 
 
Table 2. Phase III trials with Contrave (Naltrexone-Buproprion [NB]) 
Phase 3 
Study 
Arms  
Study population (BMI ≥30 or 
≥27 w/comorbidities and ≤45) 
≥5% Weight 
loss at 56 weeks 
≥10% Weight 
loss at 56 weeks 
NB-301 
COR-I95 
Placebo (581) 
NB16 (578)  
NB32 (583) 
Age 18-66 
Male 15%, Female 85% 
Placebo: 16% 
NB16: 39% 
NB32: 48%
Placebo: 7% 
NB16: 20% 
NB32: 25%
NB-302 
COR-II96  
Placebo (202) 
NB32 (591)  
W/lifestyle 
change
Age 19-65 
Male 10%, Female 90% 
Placebo: 42% 
NB32: 66% 
 
Placebo: 20% 
NB32: 41% 
NB-303   
COR-
BMOD97
Placebo (495) 
NB32 (1001) 
***NB48 (123) 
Age 18-65 
Male 15%, Female 85% 
Placebo: 17% 
NB32: 50% 
Placebo: 6% 
NB32: 28% 
NB-304 
COR-
T2DM
Placebo (170) 
NB32 (335) 
Age 20-72 
Male 44%, Female 56% 
Placebo: 19% 
NB32: 45% 
Placebo: 6% 
NB32: 18% 
*NB16 (Naltrexone SR 16mg/day and Buproprion SR 360mg/day) 
**NB32 (Naltrexone SR 32 mg/day and Buproprion SR 360mg/day) 
*** From week 28-44, nonresponders on NB32 were re-randomized to either continue NB32 or 
change to Naltrexone SR 48mg/day and Buproprion SR 360mg/day 
A recent multicenter, randomized, controlled, open-label trial examined weight-related quality of 
life, control over eating behavior and sexual function after 26 weeks of treatment with either 
naltrexone 32 mg with bupropion 360 mg plus a comprehensive lifestyle intervention (NB + 
CLI, N = 153) or usual care (UC, N = 89), which included minimal lifestyle intervention. 
Compared with UC, participants treated with NB + CLI experienced greater improvements in 
weight-related quality of life, control over eating behavior, and sexual function. NB + CLI and 
UC participants lost 9.46 and 0.94% respectively of initial body weight at week 26 (P < 0.0001). 
NB + CLI participants had greater improvements in IWQOL-Lite total score than UC 
participants (P < 0.0001). In participants with moderate/severe Binge Eating Scale scores at BL, 
91% of NB + CLI and 18% of UC participants experienced categorical improvements. In 
participants with Arizona Sexual Experiences Scale-defined sexual dysfunction at BL, 58% of 
NB + CLI and 19% of UC participants no longer met dysfunction criteria at week 2698.  
5.10 Patient Reported Outcomes (PROs) 


 
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Being overweight or obese has an important impact on patients’ functioning and well-being, 
particularly physical function99. Thus, it will be important to assess the impact of weight loss and 
POWER-remote on patient-reported outcomes, including pain, fatigue, mental well-being, 
physical function, endocrine symptoms, sleep, sexual function, and medication adherence. The 
original POWER study investigated PROs using the MOS SF-12 physical component summary 
and mental component summary, the EuroQoL-5 dimensions single index and visual analog 
scale, the Patient Health Questionnaire-8 (PHQ-8) depression symptoms, and the Pittsburgh 
Sleep Quality Index (PSQI) sleep quality scores at baseline and 6, 12 and 24 months. We will 
notify the primary oncology provider if the PHQ-8 score is ≥15 (moderately severe or severe 
depression).   
Physical domains were most affected, especially in subjects who lost weight. In another study 
which involved postmenopausal women undergoing a dietary and/or exercise intervention, 
weight loss predicted improvement in self-reported physical function, vitality, and mental 
health100. Since physical function has most consistently been found to be improved by weight 
loss, it will be our primary PRO. Studies in cancer patients suggest a 4-6 point change in score in 
Physical Function using the National Institute of Health (NIH) Patient-Reported Outcome 
Measurement Information System (PROMIS) questionnaire to be clinically meaningful101.  Since 
minimally important differences is usually estimated by taking half the estimated standard 
deviation, and in conjunction with the aforementioned studies, we conservatively hypothesize 
that, compared to baseline, weight loss at 6 months will be associated with an increase of five 
points in PROMIS, as determined by version 1 short-form to assess physical function. This form 
was also used in the POWER-remote study.  
We will also administer a questionnaire to evaluate modulation in other PROs including: pain, 
fatigue, mental well-being, sleep, endocrine symptoms, and sexual function. Participants will 
also complete a drug diary to monitor medication adherence.  
5.11 Summary  
Treatment of obesity with pharmacotherapy is underutilized in patients whom are unable to 
achieve weight loss with behavioral interventions. Our results will be used not only to implement 
a weight loss program for this vulnerable population of breast cancer patients, but also to develop 
large scale trials assessing breast cancer-related outcomes. Furthermore, we will identify how 
pharmacotherapy and behavioral weight loss interventions affect biomarkers of obesity and the 
microbiome, laying groundwork to future trials investigating additional or alternate interventions 
in those who are not expected to benefit from the program. 
 
6. INCLUSION AND EXCLUSION CRITERIA 
This is a single arm phase II study designed to determine the effects of pharmacotherapy and a 
POWER-remote weight loss intervention implemented as part of routine oncology practice, and 
the impact of successful weight loss on serum biomarkers of obesity that may be used to design 
future studies.  
6.1 Inclusion criteria 


 
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6.1.1 Female, at least 3 months after completion of local therapy (e.g. surgery, radiation), and if 
applicable, adjuvant chemotherapy  
NOTE:  Concurrent endocrine therapy or anti-HER2 therapy is permitted. Concurrent enrollment 
in other interventional or drug clinical trials is at the discretion of the Protocol Chair. 
6.1.2 Diagnosed within 15 years with histologically-confirmed ductal carcinoma in situ (DCIS) 
or stage I-III invasive carcinoma of the breast   
6.1.3 Up to date with recommended screening mammography within one year 
NOTE: Women who have had a mastectomy (including simple mastectomy, modified 
radical mastectomy, and radical mastectomy) to treat breast cancer need no further routine 
screening mammograms on the affected side. If both breasts are removed (a double or 
bilateral mastectomy), they don't need mammograms at all. 
NOTE: Women who have had breast-conserving surgery (e.g., partial mastectomy or 
lumpectomy) should have a mammogram of the treated breast 6 to 12 months after radiation 
treatment ends. After that, women should have annual mammograms. 
6.1.4 Current BMI ≥ 30 kg/m2 or BMI 27.0-29.9 kg/m2 with hypertension, non-insulin 
dependent diabetes or hyperlipidemia; and weight ≤ 400 lbs  
NOTE:  Participants should not have weight loss greater than 5% of body weight in the last 6 
months.  All weights for determination of eligibility may be determined by self-report of weight 
if not documented in the medical records.  During the study, if any surgical procedures are 
required, the difference between weight prior to surgery and after surgery will be accounted for 
and require notification of the Protocol Chair/designee. 
6.1.5 Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix A) 
6.1.6 Willingness to change diet, physical activity, track behaviors, engage in weekly and 
monthly contacts and visit, and take chronic weight loss medication 
6.1.8 Able to read and write the English language without assistance and daily access to the e-
mail and/or smartphone 
NOTE:  Participants who are unable to receive email or to complete the online questionnaires for 
any reason will not be eligible for the study.  
6.1.9 Patient is aware of her diagnosis, understands the study regimen, its requirements, risks, 
and discomforts, and is able and willing to sign an informed consent form.  
6.2 Exclusion criteria 
6.2.1 Serious/uncontrolled medical condition at the discretion of the Protocol Chair/designee 
likely to hinder accurate measurement of weight or any condition for which weight loss is 
contraindicated or would affect adipokine and inflammatory markers (e.g. active malignancy, 
end stage renal disease on dialysis, cirrhosis, autoimmune disease, adrenal disease, uncontrolled 
hypertension, seizure disorder, and history of bariatric surgery) 
6.2.2 Pregnant or nursing within past 6 months, or plans to become pregnant in the next year 


 
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6.2.3 Currently enrolled or planning to enroll in a weight loss program (e.g. Weight Watchers, 
Jenny Craig, Nutrisystem and Medifast) or to take a chronic weight loss medication. 
6.2.4 Diabetes on insulin or sulfonylureas within the past 3 months 
6.2.5 Unstable psychiatric disorder or bulimia/anorexia nervosa 
6.2.6 Alcohol, nicotine or substance abuse; or undergoing abrupt discontinuation of alcohol, 
benzodiazepine, barbiturate or anti-epileptic drug 
6.2.7 Use of the following medications are excluded:  
 Tamoxifen 
 MAO inhibitors (must be >14 days from discontinuation) 
 Thyroid medication use unless on stable doses for at least the past 3 months 
 Buproprion containing products or opiate agonists (must be >14 days from 
discontinuation) 
 Medications that cause weight loss (e.g., lorcaserin, phentermine, orlistat, Qsymia, 
Contrave) within the past 3 months 
 Medications that are likely to cause weight gain or prevent weight loss (e.g., 
corticosteroids, lithium, olanzapine, risperidone, clozapine, oral contraceptive pills, 
hormone replacement therapy) within the past 3 months. NOTE: An exception to this 
is that SSRI’s and SNRI’s are allowed if participant has been on stable doses for at 
least 3 months (if discontinued, a washout of 2 weeks from prior SSRI/SNRI use is 
required).  
 Medications that may affect adipokine or inflammatory markers (e.g., metformin, 
glitazones, steroids, ACE inhibitors, beta blockers and statins) unless on stable doses 
≥3 months prior to registration (if discontinued, a washout of 2 weeks from prior use 
is required).  Concurrent NSAIDs are allowed if use is limited to <3 times per week; 
chronic NSAIDs are permitted on study only if use has been ≥3 times per week for at 
least 3 months prior to registration and is expected to continue. 
NOTE:  No medication should be discontinued without guidance of the prescribing provider. 
6.3 Inclusion of women and minorities 
Women of all races and ethnic groups are eligible for this trial. There is no bias towards age or 
race in the clinical trial outlined. This trial is open to enrollment of women only. 
 
7. STUDY DESIGN AND TREATMENT PLAN 
7.1 Recruitment 
Patients will be recruited through the breast cancer clinics at Johns Hopkins Medical Institute, 
including the Sidney Kimmel Comprehensive Cancer Center in Baltimore MD and Green Spring 
Station in Lutherville-Timonium MD, and Sibley Memorial Hospital in Washington D.C. 
Participants will also be recruited at LHAAMC in Annapolis MD. Study participants will be 
prescreened by the Johns Hopkins breast cancer survivor registry from 2015-2019. Patients can 
also be recruited directly through these clinics. We have previously established our ability to 


 
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recruit patients with similar characteristics to a POWER-remote study4. Additionally, we are 
including a recruitment letter from the study Protocol Chair and study oncologist to send to clinic 
patients that we have been unable to reach by phone. We have also uploaded an online screener 
that will be administered via REDCAP. The purpose of the screener is to aid in visibility of the 
study and initial assessment of eligibility. We find that giving interested individuals immediate 
feedback on their initial eligibility helps them remain interested in the study until the coordinator 
can call them back. Recruitment may be expanded to include eligible breast cancer survivors in 
the region with flyers.  
7.2 Determination of Eligibility 
After eligibility is established by the coordinator during the screening call, the study staff will 
register participants, assign a study number, and schedule an in-person baseline visit. Participants 
will not begin protocol-specified treatment until eligibility is confirmed by the study staff at the 
baseline visit. Participants who sign a consent form, but do not initiate protocol intervention for 
any reason, will be replaced and will not count towards our accrual goal. 
 
 
7.3 Visits and Follow up 
The study will include a 24-month recruitment period, a 6-month implementation period, which 
involve 3 in-person visits and at least 16 phone sessions for each participant. We anticipate 
enrolling 2-4 participants per month. All women will receive the POWER remote behavioral 
weight loss intervention (BWL) and a behavioral coach. They will all receive lifestyle guidelines 
(See Appendix B). At week 9, those who lose ≥5%, designated fast responders, will continue 
with BWL alone (FAST-BWL) while those who lose <5%, designated slow responders, will 
receive BWL with the addition of Contrave (SLOW-BWL).  
Women in SLOW-BWL will initiate Contrave one 8-mg naltrexone/90-mg bupropion tablet per 
day and increased over 3 weeks to the maintenance dosage of two 8-mg/90-mg tablets twice 
daily, for a total daily dose of 32mg/360mg. It should be taken by mouth in the morning and in 
the evening and should not be cut, chewed, or crushed. In clinical trials, Contrave was 
administered with meals. However, it should not be taken with a high-fat meal because of a 
resulting significant increase in bupropion and naltrexone systemic exposure. As patients are 
instructed to follow the DASH (Dietary Approaches to Stop Hypertension) and/or Mediterranean 
diet, this should not be an issue. Patients will be instructed that ketogenic and low carbohydrate 
diets would impact the absorption of Contrave.  
The behavioral coach will review the weekly weight and new symptoms entry (patient will 
completed in REDCap survey or via telephone if not done) for months 3-6 for participants in 
both arms. The REDCap survey (Appendix C) asks patients about any new symptoms and 
includes examples of those which had a frequency of at least 4% in patients on Contrave in 
clinical trials. Any new symptoms noted will be directed to the Protocol Chair for further 
evaluation. If patients on Contrave have significant adverse effects, providers will decrease the 
dose by 50% and assess tolerability over 1 week. If symptoms are alleviated, patient can 


 
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continue at lowered dose. If symptoms persist, dose can be lowered by 50% again. If symptoms 
are alleviated, patient can continue at lowered dose. However, if symptoms persist, the 
medication should be discontinued and the patient should continue with BWL alone. Following 
the prescribing information, Contrave will be discontinued for patients who do not achieve ≥5% 
and seen in person once a month to assess compliance and potential side effects.  
The weight loss intervention is based on the remote-support arm of the POWER trial that was 
also used by our team in a previous study in breast cancer survivors3,4. It involves two main 
components: an online portion that participants access on their computer or phone and a 
telephone/teleconferencing portion to help monitor progress and deliver the behavioral 
intervention. All participants will receive the POWER intervention, which will be remote and 
last 6 months. Participants will be given a physical activity monitor (Fitbit) that encourages 
increased activity by measuring steps and process variables, such as heart rate and sleep. 
Participants will use a web-based platform to access learning materials and log their diet and 
exercise each day. They will also record their weight once weekly through our survey. As 
participants monitor their own progress, they will receive telephone/teleconferencing calls on a 
regular schedule by a weight loss coach to help monitor and guide progress utilizing dietary, 
physical activity and weight information. All contacts will be phone/teleconferencing based and 
last about 30 minutes. For all participants, contacts will occur weekly during the first 3 months (a 
baseline visit followed by 12 phone sessions) and monthly for the remaining 3 months (3 phone 
sessions). At the conclusion of the study after 6 months of behavioral intervention, participants 
will have an in-person visit.  
7.3.1 Screening (by phone call) 
 Informed consent  
 History and physical information will be noted from most recent, standard of care 
assessment included in the medical records.  (NOTE:  Participants who may be referred 
from outside the institution may meet with a medical/clinical member of the study staff at 
baseline; however, a documented H&P by a study team member is not required.) 
 Physical measurements (weight and height) as per patient or chart for BMI calculation 
 Review of weight loss history 
 Collect current medications and medication history 
 Smartphone access and/or access to programs online 
 Assess willingness to change diet, physical activity, track behaviors, engage in weekly 
and monthly contacts and visit, and take chronic weight loss medication (yes/no question 
format) 
 Through REDCap, baseline questionnaire should be completed at home ≤2 weeks prior to 
baseline visit, but may be completed at baseline visit too.  As noted in the eligibility, 
participants that are unable to complete the questionnaires will not be able to 


 
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continue/enroll in the study.  NOTE: Patients who complete a screening visit, but who are 
not eligible, will be offered the “Aim for healthy weight” handout (Appendix D).  
7.3.2 Baseline Visit 
The Baseline Visit is in-person and should ideally occur within 8 weeks of the screening visit; 
with baseline questionnaires completed ≤8 weeks prior. 
 Written informed consent 
 Physical measurements (weight and height) and BMI calculations 
 Vital signs (temperature, blood pressure, heart rate, breathing rate, oxygen level) 
 Complete medical history and overall general health (performance status) 
 If a documented physical exam is not performed within 3 months, this will be performed 
at or after baseline visit (but before initiation of the behavioral intervention) 
 Meet with weight-loss coach  
 Receive Fitbit device for monitoring physical activity (participants will wear this on their 
non-dominant hand for a minimum of 4 of 7 days with 10 hours per day) 
 Receive weight scale 
 Check heart rate and blood pressure 
 Confirm current medications and medication history  
 Blood sample (Pregnancy test for < 60 years of age and not taking medication designed 
to suppress ovarian function. Will advise contraception for these women.) 
 Fecal sample 
 Orientation to Fitbit website or smartphone platform by coordinator or coach 
 Confirm completion of PROs (or complete in clinic, if needed) 
 
IMPORTANT:  Eligibility will be confirmed at the baseline visit.  Participants with a BMI of 
≥27 at the screening visit, but with a BMI of <27 at the baseline visit will not have 
maintained eligibility and will be excluded at present. In addition, if there is ≥2 kg/m2 
discrepancy between the screening and baseline visits, the Protocol Chair or designee must 
be consulted to review the discrepancy; this is to determine that the study endpoints will not 
be affected by fluctuating/changing weight. 
7.3.3 Follow-Up Visits 
Participants will be asked to attend in-person follow-up visits at 2 months and 6 months. 
All Follow-Up Visits are in-person and should ideally occur within 8 weeks of the assessment 
visit date. 
2 months 
 Weight and BMI calculations 
 Confirm completion of PROs (or complete in clinic, if needed) 
 Confirm current medications and medication history 
 Blood samples* 
 Fecal sample 


 
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6 months (End of study) 
 Weight and BMI calculations 
 Confirm completion of PROs (or complete in clinic, if needed) 
 Collect current medications and medication history 
 Blood samples* 
 Fecal sample 
*Blood will be collected while patient is fasting when possible (i.e., 9-12 hours preferred). Will 
provide patients with juice or bar after labs. Additionally, participants will be asked to be fasting 
for follow-up visits even in cases when blood samples are not planned to allow for consistency of 
anthropomorphic data collection.  
In participants who discontinue early, the next planned assessments will be completed early 
whenever possible (e.g., a participant that withdraws at 6 weeks will be asked to complete week 
9 assessment; a participant withdraw at 5 months, the end of study assessment). The last visit 
should be scheduled once the participant has received the full 6 month intervention. 
 
7.4 Measurements 
7.4.1 Weight: will be measured at each in-person visit, at approximately the same time of day. 
The weights are obtained at baseline, week 9 and at the end of study. The ideal weight 
measurement should be obtained within 7 days of completing the 8 weeks and 6 months 
behavioral intervention. However, to accommodate participants who may not be able to meet 
within this window, the weight measurement can be obtained within 14 days of these time 
points. Weight in light indoor clothes without shoes will be recorded by any trained, certified 
staff using a high-quality digital scale in any of our Johns Hopkins Medical Institute (JHMI) 
clinics. Duplicate measurements will be made to ensure accuracy. Weight will be measured in 
pounds for ease of interpretation by the participants and subsequently converted to kilograms for 
data analysis. Scales will be calibrated per the Sidney Kimmel Comprehensive Cancer Center’s 
(SKCCC) standards.  The engineering department or study staff will perform quarterly 
calibration checks by using standard weights. The weight at SV will be used to determine 
eligibility. Measurements will be repeated once, if difference between the two measurements is 
more than 0.1 kg, measurement will be repeated until difference between two measurements is 
less than 0.1 kg.  
7.4.2 Height: to the nearest 0.1 cm will be measured once at any of our JHMI clinics. The 
participant stands shoeless on a firm, level surface, with her head in the horizontal (Frankfort) 
plane. Measurements will be repeated once, if difference between the two measurements is more 
than 1 cm, measurement will be repeated until difference between two measurements is less than 
1 cm. 
7.4.3 BMI: will be calculated as the Quetelet index (kg/m2) 


 
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NOTE:  All physical measurements should be taken by a member of the study team or an 
appropriate clinical employee (e.g., clinical associate who regularly collects physical 
measurements). 
7.4.4 Daily steps: are measured by Fitbit. Fitbit devices use a 3-axis Fitbit to understand your 
motions. An Fitbit is a device that turns movement (acceleration) into digital measurements 
(data) when attached to the body. 
7.4.5 Intensity of physical activity (also known as MVPA, which is moderate to vigorous 
physical activity): is measured by the Godin Leisure-Time Exercise Questionnaire. Leisure-time 
physical activity is an important subtype of physical activity (PA) for research and behavior 
change intervention in oncology context. This is a 3-item self-administered questionnaire with 
the first three questions seeking information on the number of times one engages in mild, 
moderate and vigorous PA bouts of at least 15 min duration in a typical week. Examples of PA 
are provided for each intensity category. Scores derived from the questionnaire include total 
weekly PA, called a Leisure Score Index (LSI), in which number of bouts at each intensity is 
multiplied by 3, 5, and 9 metabolic equivalents (METs) and summed. LSI scores can be used for 
ranking individuals from the lowest to highest PA levels. In addition, the score obtained from 
MVPA can be used to classify respondents into active and insufficiently active categories 
according to published PA guidelines for cancer survivors.  
7.5 Questionnaires 
7.5.1 Clinical and Demographic Information  
The designated research coordinator(s) participating in this project will enter clinical information 
associated with each participant in the database. Such data could include, but is not limited to: 
medical record number, age, sex, physical measurements, treatment history, tumor size, tumor 
grade, tumor receptor status, pathology report, smoking history. Such information will be 
retrieved from existing clinical databases (e.g., Johns Hopkins Electronic Patient Record) and 
patient questioning.  
Participants will be asked to provide contact information for their other health care providers in 
case information needed is not contained in the Hopkins clinical databases, or if the participant 
assumes care outside the institution. In addition, participants may be reached by phone to help 
with any questions or clarifications, or additional follow-up requirements.  
Participants will also be asked about current medications at each visit. This will be documented 
in the electronic medical record. 
7.5.2 Patient Reported Outcomes 
We will collect PROs using REDCap, which is already in throughout the institution by several 
clinical investigations. PROs will include questionnaires regarding physical function, pain, 
fatigue, mental well-being, endocrine symptoms, sleep, sexual function, and medication 
adherence, at baseline, 2, and 6 months following initiation of the intervention. Pain, fatigue, 
mental well-being, sleep, and physical function will be assessed using the NIH PROMIS 
questionnaire; endocrine symptoms with the FACT-endocrine symptoms, and sexual function 


 
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with the MOS-Sexual Function. Medication adherence will be monitored with the institutional 
drug diary.  
Enrolled patients will be given a letter with a username and password for the Fitbit website, and 
will be oriented on how to use the website; an email address will also be recorded for each 
participant.  Participants will receive e-mail reminders when it is time for them to complete the 
REDCap questionnaire. They will be encouraged to complete the questionnaire prior to any 
planned clinic visit; however, they will be informed that a research coordinator can assist them 
prior to their visit if they prefer to complete the questionnaire at the clinic. Whether patients 
complete the PRO questionnaire at home or in the clinic, they will access the questionnaires via 
the internet. At follow-up clinic visits for patients who completed the PRO questionnaires, 
clinician sub-investigators will have a summary report available to them via REDCap.  
Questionnaires will focus on some basic background information and patient reported outcomes, 
with more detailed survey information as follows. Data from the questionnaires will be available 
for export into spreadsheets or other tools for analysis. 
NOTE: In the event that questionnaires through REDCap are not available, we will use paper-
based questionnaires.  
The questions that will be included in the REDCap system are included in Appendix E. Score 
interpretation is in Appendix F.  Domains that will be included in REDCap are as follows: 
 General health and physical function will be assessed using NIH PROMIS Adult Physical 
Function Short Form 1102. The physical function item bank measures self-reported 
capability rather than actual performance of physical activities, and generally includes the 
functioning of one’s upper extremities (dexterity), lower extremities (walking or 
mobility), and central regions (neck, back), as well as instrumental activities of daily 
living, such as running errands. A single physical function capability score is obtained 
from a short form, and has been validated in adults with chronic illnesses. 
 Pain will be assessed using the NIH Patient-Reported Outcome Measurement Information 
System (PROMIS) adult pain interference version 1.0 short form. The pain interference 
item bank measures the self-reported consequences of pain on various aspects of daily 
life. This includes the extent to which pain hinders involvement in social, cognitive, 
emotional, physical, and recreational activities. The short form is comprised of 6 
questions which assess pain interference over the previous seven days. Each question has 
five response options ranging in value from one to five. A total raw score is calculated by 
summing the values of the response to each question, and then translated into a T-score 
using a conversion table. The T-score rescales the raw score into a standardized score 
with a mean of 50 and a standard deviation (SD) of 10. Therefore, a person who has a T-
score of 40 is one SD below the U.S. general population mean. Reliability and validity 
have been previously reported103. 
 Fatigue will be measured using the NIH PROMIS Adult Fatigue Version 1.0 short form. 
The NIH fatigue question bank evaluates a range of self-reported symptoms, from mild 
subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of 
exhaustion that likely decreases one’s ability to execute daily activities and function. 
Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and 


 
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the impact of fatigue on physical, mental, and social activities. The short form used has 7 
questions which assess fatigue over the past seven days. As with all of the PROMIS short 
forms, each question has five response options ranging in value from one to five. A total 
raw score is calculated by summing the values of the response to each question, and then 
translated into a T-score using a conversion table. The T-score rescales the raw score into 
a standardized score with a mean of 50 and a standard deviation (SD) of 10. Therefore, a 
person who has a T-score of 40 is one SD below the U.S. general population mean. 
Reliability and validity of the fatigue assessment in cancer patients has been reported104. 
 Mental health will be evaluated using the NIH PROMIS Depression and Anxiety 
questionnaires. The Adult Depression Version 1.0 Short Form is an 8 question survey, 
and the Adult Anxiety Version 1.0 Short Form is a 7-item survey, for a total of 15 mental 
health questions. The depression item bank assesses self-reported negative mood 
(sadness, guilt), views of self-criticism, worthlessness), and social cognition (loneliness, 
interpersonal alienation), as well as decreased positive affect and engagement (loss of 
interest, meaning, and purpose). The anxiety item bank measures self-reported fear 
(fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, 
restlessness), and somatic symptoms related to arousal (racing heart, dizziness). The 
anxiety and depression scores are calculated individually, in the same way all PROMIS 
scores are calculated as above. 
 Endocrine symptoms will be assessed using the endocrine subscale of the Functional 
Assessment of Cancer Therapy-Endocrine Symptom questionnaire. The Endocrine 
Subscale was designed for use with the FACT-B (Functional Assessment of Cancer 
Therapy for breast cancer patients) but has been tested on its own105. It comprises 18 
items in which patients indicate how true a statement has been for them over the prior 7 
days using a 5-point scale.  
 Disturbance in sleep or sleep changes on therapy will be evaluated with the NIH 
PROMIS Adult Sleep Disturbance Version 1.0 Short Form. The sleep disturbance item 
bank assesses self-reported perceptions of sleep quality, sleep depth, and restoration 
associated with sleep over the 7 days before questionnaire administration. This includes 
perceived difficulties and concerns with getting to sleep or staying asleep, as well as 
perceptions of the adequacy of and satisfaction with sleep106. 
 Changes in sexual function will be evaluated using the MOS Sexual Functioning Scale, 
which consists of four items assessing interest in sex, ability to relax and enjoy sex, 
arousal, and ability to have an orgasm. Items are rated on a 5-point scale (1=not a 
problem, 2=little of a problem, 3=somewhat of a problem, 4=very much of a problem, 
and 5=not applicable). This scale is useful for measuring sexual function in both men and 
women. It has demonstrated good reliability and construct validity in breast cancer 
patients107. 
 Medication adherence will be assessed using the institutional drug diary (APPENDIX G).  
7.5.3 Nutritional and Physical Activity Assessments 
Fruit and vegetable consumption will be measured with National Institutes of Health’s Eating at 
America’s Table study108.  Participants will be asked various questions regarding the frequency 
and quantity of various food groups in the past month. A total score is calculated by converting 


 
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quantity to a standard scale for each food category, multiplying by the frequency, and summing. 
This questionnaire will be implemented at baseline and follow-up visits (See Appendix E and F). 
Participants will wear the Fitbit on their non-dominant hand for seven days and a minimum of 
four days with ten hours per day of wear time required for analyses. Fitbits have been determined 
to be reliable and valid measures of physical activity109. Established cut-points will be used to 
determine minutes of moderate to vigorous physical activity110. Average daily physical activity 
will be normalized and reported as minutes per week of moderate to vigorous physical activity. 
The Fitbits will also capture process variables, such as heart rate and steps.  
7.6 BWL intervention 
All patients enrolled will receive a 6 month remotely delivered behavioral lifestyle intervention 
primarily through a web-based platform. For purposes of this study, lifestyle coaches will be 
supplied by Johns Hopkins. The coaches are trained in both behavioral weight loss principles and 
motivational interviewing will have access to self-monitoring data through the platform, 
allowing them to review multiple aspects of adherence to dietary and physical activity behaviors 
as well as weight loss progress.  To tailor the intervention to breast cancer survivors, we have 
provided the coaches with comprehensive training regarding breast cancer subtypes, types of 
therapy patients have received and might still be taking (e.g., hormonal, anti-HER2 agents), 
expected side effects from prior or ongoing therapy (e.g., fatigue, neuropathy, lymphedema, hot 
flashes), scheduled standard clinic visits and tests, and symptoms disconcerting for a recurrence. 
Coaches will discuss additional dietary and physical activity recommendations that are standard 
for breast cancer patients such as moderation of alcohol intake. Patients are provided with 
modules of recommended exercises per American College of Sports Medicine and American 
Cancer Society recommendations, particularly in reference to lymphedema prevention111.  
The participants will have access to a web-based platform which provides support for lifestyle 
counseling in behavioral methods of weight management; a summary of the support and methods 
will be given at the first/in-person visit with the weight loss coach. Participants in this group will 
be encouraged to record diet, exercise, and weight on this web-based platform. Web-links to 
health related websites may also be left by the coach. These participants will receive usual 
medical care from their providers (i.e., oncologists and primary care physicians). Providers will 
support and encourage participants to be actively engaged in the lifestyle counseling 
intervention.  
7.6.1 Goals 
The goals of this intervention (from months 3-6) are to induce weight loss of 5% or more by 
adding pharmacotherapy to behavioral weight loss interventions in women whom are unable to 
achieve 5% weight loss with lifestyle modifications alone. 
7.6.2 Description and delivery of the intervention 
Participants in this group will receive a behavioral weight loss intervention consisting of:  
 
Teleconferencing and/or phone calls by coaches (see frequency of contacts below);  
 
A lifestyle counseling curriculum delivered via the web (hard copies also provided as 
requested); and  


 
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 
Online tools for behavioral self-monitoring.  
7.6.3 The lifestyle curriculum: 
The lifestyle curriculum consists of learning materials which will be provided in a binder and can 
be provided electronically. The curriculum focuses on self-monitoring, behavioral strategies for 
modifying eating behavior and increasing physical activity, stimulus control, social support, 
problem solving, and cognitive restructuring. Goal setting is also a key component of the 
intervention.  
7.6.4 Self-Monitoring 
All participants are advised to:  
 
Record weight at least once each week.  
 
Record daily: minutes of moderate to vigorous physical activity (MVPA) in bouts of 10 
minute bouts or more, and all food and beverages consumed daily using the smartphone 
application or website.  
7.6.5 Participant contact 
Participants receive teleconferencing/telephone calls weekly for 3 months and monthly thereafter 
from lifestyle coaches to encourage completion of learning materials modules, to reinforce key 
learning points, and to encourage logging and provide feedback on weight, food intake, and 
exercise tracking. Calls will be each week for months 1-3, once a month for months 4-6. Each 
call will be approximately 30-45 minutes long. For all participants, coaches will also review 
and/or inquire about any new symptoms (weekly during months 4-6) and adherence if they are 
assigned to the arm with the pharmacotherapy. If symptoms are reported, the coach will notify 
the physician on study and the patient may be contacted by the physician for further evaluation.  
7.6.6 Assessment of adherence 
Adherence to intervention for participants will be based on completion of coach contacts and 
modules, and online self-monitoring of weight, food intake, and exercise. Additionally, patients 
on the SLOW-BWL arm will complete a drug diary log during the one-month long titration 
(APPENDIX G). Patients will e-mail their logs to the study team for review.  
7.6.7 Provider role 
At routine medical visits, these participants will be encouraged by their oncologist to actively 
engage in the intervention. Providers will receive a report that provides a snapshot of their 
patient’s progress and that provides key behavioral recommendations to reinforce. 
7.6.8 Description of BWL Intervention 
Month 1-3
Frequency
Weekly
Entire duration of study 
Automated weekly weight entry 
Mode
Teleconferencing or phone calls 


 
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The SLOW-BWL group will have the addition of Contrave to BWL from Month 4-6 
*From months 4-6, for any patients in either arms who are struggling with weight loss (i.e. 
motivation, behavioral concerns, weight regain etc.), an additional 2 “booster” visits can be 
scheduled through teleconferencing sessions. 
 
7.6.9 Weight Goals and Behavioral Recommendations 
Remote-Support Weight Loss Intervention
Weight Loss Goal 
Minimum 5% weight loss, individually tailored
Behavioral Recommendations
Total Calorie Intake 
Active weight loss 
1200 kcal/d if ≤ 170 lbs 
1500 kcal/d if > 170 lbs and < 200 lbs 
1800 kcal/d if > 200 lbs and < 270 lbs 
2200 kcal/d if > 270 lbs 
Maintaining weight loss 
1500 – 1900 kcal/d 
Dietary Pattern 
Option 1: DASH diet 
7-12 servings of fruits/vegetables 
2-3 servings of low fat dairy 
Low sodium 
≤ 25% of calories from fat 
Option 2: Mediterranean diet 
Daily consumption of vegetables, fruits, whole grains 
and healthy fats 
Weekly intake of fish, poultry, beans and eggs 
Moderate portions of dairy products 
Limited intake of red meat and alcohol
Physical Activity 
Build to ≥ 180 minutes/week of moderate intensity physical 
activity in bouts ≥ 10 minutes in length
Self-Monitoring Recommendations 
Weight
Weekly
Calorie counting
Daily
Physical activity
Daily
Mode
Online behavioral tracking of above behaviors
7.7. Concomitant and Supportive Therapy 
In general, concomitant medications and therapies deemed necessary for the supportive care and 
safety of the subject are allowed, provided their use is documented in the medical records. Any 
Month 4-6
Entry of diet and exercise 
Frequency
Monthly
Mode
Teleconferencing or phone calls


 
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changes in medications during the study must be clearly documented in the study records.  The 
administration of any other therapies intended to treat the breast cancer, with the exception of 
trastuzumab (Herceptin®) and endocrine treatment (i.e., aromatase inhibitor) is NOT permitted.  
As noted, changes in endocrine treatment during study participation should be avoided.  The 
initiation of or changes to any ongoing medications listed in Section 6.2.4 should also be 
avoided, if possible.  
7.8 Discontinuation and withdrawal of subjects 
Participants who discontinue the study early will be asked to complete the next planned 
assessment at the time of discontinuation, if feasible and acceptable to the patient. All reasons for 
discontinuation of therapy should be documented clearly in the medical record. 
7.11 Discontinuation of intervention 
The intervention will continue for the planned 6 months except in patients who fulfill one or 
more of the following criteria:  
 Diagnosis of new or recurrent intraductal or invasive breast cancer while on therapy 
where a change in treatment is planned. 
 Intercurrent illness or change in the patient’s condition that renders the patient 
unacceptable for further treatment in the judgment of the principal investigator (PI). 
 Pregnancy  
 Lack of compliance with treatment assignment. 
 Patient request to discontinue protocol.  
7.12 Withdrawal from Study 
The reasons for withdrawal from the study include:  
 Subject withdraws consent. 
 Subject needs treatment not allowed in the study.  
 Study is lost to follow-up. 
 Study is canceled for any reason. 
7.13 Additional Information 
 Participants who complete the study will be gifted the Fitbit and weight scale in appreciation of 
their time at the final study visit.  Participants will also be offered parking vouchers at the end of 
each study visit, if applicable. Additionally, for patients who have completed the study and 
would like to continue weight management care within Johns Hopkins, the team will provide 
referrals to the Digestive Weight Loss Center (at Green Spring Station, Sibley Memorial 
Hospital or Johns Hopkins Hospital).   This information will be included in the informed consent 
document. 
 
 
 


 
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8. STUDY CALENDAR 
Procedure 
Screening call 
for eligibility 
Baseline 
Visit ## 
Follow-Up Visits ## 
Week 9
 
Month 6 
Clinical & Physical Assessments:  
Consent 
 
X 
 
 
 
Questionnaires 
 
X 
 
 
 
History 
X 
 
 
 
 
Physical exam 
 
X# 
 
 
 
Current medications 
X 
X 
 
 
 
Performance status 
 
X 
 
 
 
Weight Loss History 
X 
 
 
 
 
Vitals 
 
X 
X 
 
X 
Up to date screening 
mammography within one year
X 
 
 
 
 
BMI Calculation  
X* 
X 
X 
 
X 
Anthropomorphic Measurements:  
Height  
X* 
X 
 
 
 
Weight 
X* 
X 
X 
 
X 
Research Correlates:  
Fecal sample 
 
X 
X 
 
X 
Serum pregnancy test (if age 
<60)
 
X 
 
 
 
Lipid panel, Hba1c  
 
X 
X 
 
X 
Purple research tube 
 
X 
 
 
 
Red/gray research tube 
 
X 
X 
 
X 
Research Intervention: 
Patient Reported Outcomes 
 
X 
X 
 
X 
Provide Fitbit** 
 
X 
 
 
 
Coaching (BWL 
intervention)***
 
X 
X 
 
X 
Provide weight scale 
 
X 
 
 
 
*If greater than 3 months since last documented height and weight in electronic health record, 
will use patient reported most recent height and weight to determine eligibility based on BMI. 
However, BMI measured at baseline will serve as first data point.   
**Participants will wear the Fitbit on your non-dominant hand for 7 days and a minimum of 4 
days with 10 hours per day of wear time.  
***Participants will communicate with their coach by phone. The coach will reach out to the 
participants at the baseline visit, and will provide weekly calls and emails the first 3 months. The 
last 3 months, participants will receive monthly calls and emails.  


 
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# Physical exam: may be performed and documented up to 3 months prior to baseline visit by a co-
investigator or provider within the institution. Or physical exam may be performed at or after 
baseline visit (but before initiation of the behavioral intervention) 
## Baseline visits should occur within 8 weeks of screening visit. Follow up visits should occur 
within 8 weeks of assessment date.  
NOTE: Additional standard of care tests may be performed at the discretion of the treating 
investigator as clinically indicated. The schedule should be followed as closely as is realistically 
possible; however, the schedule may be modified due to problems such as scheduling delays or 
conflicts (e.g., clinic closure, poor weather conditions, vacations, etc.) with the guidance of the 
PI/designee, as appropriate, and will not be reportable as a deviation unless the endpoints of the 
study or subject safety are affected.  
In order to minimize the need for research-only in-person visits, telemedicine visits may be 
substituted for in person clinical trial visits or portions of clinical trial visits where determined to 
be appropriate and where determined by the investigator not to increase the participants risks. 
Prior to initiating telemedicine for study visits the study team will explain to the participant, what 
a telemedicine visit entails and confirm that the study participant is in agreement and able to 
proceed with this method. Telemedicine acknowledgement will be obtained in accordance with 
the Guidance for Use of Telemedicine in Research. In the event telemedicine is not deemed 
feasible, the study visit will proceed as an in-person visit. Telemedicine visits will be conducted 
using HIPAA compliant method approved by the Health System and within licensing 
restrictions. 
9. CORRELATIVE STUDIES 
9.1 Blood Samples 
9.1.1 Collection 
Approximately 15 mL (3 tubes) of blood will be collected at each time point (a standard 5 mL 
tube for lipid panel and Hba1c, one 10 mL red/gray research tubes). An additional 8 mL will be 
collected at the initial blood draw to include a 5mL red top tube for pregnancy test and 3 mL 
purple EDTA tube are collected for research once only. If blood samples are missed or unable to 
be obtained at any time point, this will not be considered a deviation and will not affect 
participant enrollment or continuation on the study. We will test glucose, insulin, lipid profiles 
(total cholesterol, HDL, LDL, and triglycerides), leptin and adiponectin, several fasting 
biomarkers, and various genotypes (e.g. MnSOD). The samples will be processed by either the 
central lab or local laboratories (See Lab Manual). In the event that blood cannot be collected, 
the subject may still take part in the other portions of the study.  
 
Baseline 
2 months 
6 months 
Standard 5 mL gold 
tube (lipid panel, 
Hba1c) 
X 
X 
X 


 
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Pregnancy test 5 mL 
red tube (if indicated) 
X 
 
 
Purple 3 mL tube 
X 
 
 
Red/gray 10 mL tube 
X 
X 
X 
9.1.2 Analysis 
Biomarkers will be processed and batch analyzed whenever possible to reduce within- and 
between-batch variability at a designated facility (e.g., the Johns Hopkins Medical laboratories 
Services).  
 
9.2 Fecal Samples 
Participants will provide fecal samples three times during the study and will be provided with the 
fecal occult blood test (FOBT) to collect the sample at home after a bowel movement. They will 
ship the fecal sample to the lab of Dr. Sharma at Johns Hopkins University. Upon arrival at the 
lab, the specimens will be stored at −80°C and will be processed for microbiome analyses. 
Analysis targeting the V4 region of the 16S rRNA gene will be performed using an Illumina 
MiSeq and analyses of the microbiome samples will be performed using the Quantitative Insight 
into Microbial Ecology (QIIME) suite, V.1.7 and a QIIME wrapper (QWRAP). 
9.3 Leftover Samples 
Any leftover study blood and stool samples will be stored for future research studies, including 
predictive biomarker studies. These samples may be released for use in future studies after 
approval by the Protocol Chair and other regulatory bodies, as appropriate. 
9.4 Additional information 
The correlative sample collection schedules outlined are based on an ideal subject. The sample 
schedule should be followed as closely as is realistically possible; however, the schedule may be 
modified due to problems such as scheduling delays or conflicts (e.g., clinic closure, poor 
weather conditions, vacations, etc). 
 
10. ADVERSE EVENTS 
10.1 General 
This study will use the descriptions and grading scales found in the revised National Cancer 
Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 for adverse 
event reporting that can be found at http://ctep.cancer.gov/reporting/ctc.html. Information about 
all related adverse events, whether volunteered by the subject, discovered by investigator 
questioning, or detected through physical examination, laboratory test or other means, will be 
collected, recorded, and followed as appropriate. 
It should be noted that only those adverse events believed to be related to the weight loss 
intervention will be collected and tabulated during the course of the study.  The side effects with 


 
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the weight loss intervention we might encounter include anxiety and frustration. While this 
program is not designed to cause radical weight loss, in the unlikely event this were to occur 
radical weight loss can cause several medical implications including dehydration, malnutrition, 
electrolyte disturbances, headaches, nausea, and tachycardia. Blood samples for research 
correlated will require intravenous access which may include discomfort, bruising and, rarely, 
infection, syncope, or significant bleeding; these will be collected at planned standard of care 
testing, whenever possible.   
10.2 Potential Risk from Intervention 
The following sections describe potential risks associated with the remote-support weight loss 
intervention along with procedures to minimize risk.   
10.2.1 Physical Activity 
During the screening process, we will exclude persons with uncontrolled medical illnesses for 
which physical activity would be contraindicated.   
In order to protect the participants' safety, we will continuously reinforce our recommendation to 
engage in moderate-intensity physical activity.  We will also recommend a safety evaluation by 
their Primary Care Physician (PCP) for those participants who wish to progress to vigorous 
physical activity.  Still, it is important to acknowledge the participant autonomy.  We can 
recommend that participants follow safety advice but cannot force them to do so.   
10.2.2 Nutrient Intake 
Calorie restriction can theoretically lead to inadequate nutrition or excessive, rapid weight loss 
(>10% weight loss within 4 weeks or a total weight loss of >25%).  If a participant loses >10% 
weight within 4 weeks, the team will review the patient’s food diary to ensure that they are not 
over restricting their calories (e.g., <1000 daily). If people achieve more than a 25% weight loss, 
then the team will evaluate for cancer (recurrence in our population), eating disorders, and 
hyperthyroidism. To minimize these risks, participants are encouraged to eat a variety of foods 
from all food groups and to maintain an adequate calorie level. If nutritional deficiency is 
suspected and unresponsive to advice from the interventionist, the intervention will be suspended 
and the participant will be referred to her PCP. Participants will be advised that marked and 
sustained caloric restriction can have serious health risks, e.g., malnutrition.  
10.2.3 Hypoglycemia  
For patients who may be susceptible to hypoglycemia due to use of anti-diabetic medications, 
weight loss interventions have the potential to increase the risk of hypoglycemia, especially 
during the time when diet and/or physical activity interventions are implemented. For this reason 
we will exclude patients who take insulin or sulfonylureas. We will allow patients to enroll if 
their diabetes is controlled on metformin. If participants have a drop in HbA1c to <6.5 or if they 
require a change in diabetic medications during this study, they will be overseen by the Protocol 
Chair and/or co-investigator and the PCP will be notified of these changes.  


 
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10.2.4 Symptomatic Hypotension  
For patients who may be susceptible to hypotension because they are using medications that 
lower blood pressure, weight-loss interventions have the potential to increase the risk of 
hypotension.  Participants are educated about symptoms of hypotension and urged to contact the 
research nurse or PCP if they have symptoms suggestive of hypotension.   In addition, staff 
contact will notify the Protocol Chairof participants who develop symptomatic hypotension 
while on anti-hypertensive medications. Changes in blood pressure regimen may be performed 
by the Protocol Chair and/or co-investigators and the participant’s PCP will be notified. 
10.2.5 Cardiovascular Events 
All participants with cardiovascular disease (CVD) require approval from their PCP and Protocol 
Chair prior to enrolling.  If this medical condition is not felt to be stable, patients will be 
excluded from this study. In addition, participants are educated about CVD symptoms and urged 
to contact their PCP if they have a change in their CVD symptoms. Overall CVD management 
remains under the control of the participant’s PCP. 
10.2.6 Symptoms Related to Contrave 
The pharmacotherapy could lead to adverse effects: nausea (NB32 29%, NB16 27%). Headache 
(NB32 13%, NB16 27%), constipation (NB32 15%, NB16 15%), dizziness (NB32 9%, NB16 
7%), insomnia (NB32 7%, NB16 6%), vomiting (NB32 9%, NB16 6%), and dry mouth (NB32 
7%, NB16 7%)95. Adverse events were most frequently gastrointestinal in nature. The most 
common of these, nausea was generally mild to moderate in intensity, transient, and did not 
result in discontinuation for most participants who reported it. Nausea was typically first reported 
during dose escalation in the experimental groups; the rate of onset seemed to plateau shortly 
after reaching full dose and then was similar to the rate reported in the placebo group. The most 
frequent adverse events leading to discontinuation before week 26 included nausea (10.5%); 
anxiety (3.3%); and headache, hypertension, insomnia and palpitations (1.3% each)98. While 
attrition across all phase III studies of Contrave ranged from 42% to 50%, only 24% of those 
taking Contrave withdrew due to adverse events (vs 12% taking placebo)93.  
Participants will be educated about the side effect profile and urged to contact the research nurse 
if they have symptoms. Depending on the severity of the side effect, the dosage may be 
decreased or discontinued entirely. Patients whom are discontinued on the pharmacotherapy will 
continue the study with BWL alone. Changes in overall management of hypertension remain 
under the control of the PI. 
10.2.6 Survey fatigue 
Minimal risks associated with completing the questionnaires include subject fatigue and the 
possibility of minor psychological distress. Participants are instructed that they may refuse to 
answer any questions. 
10.3 Definitions 
 Adverse event (AE): Any undesirable sign, symptom or medical condition occurring after 
starting therapy even if the event is not considered to be related to the study. An 
undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., 


 
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tachycardia) or the abnormal results of an investigation (e.g., laboratory findings, 
biopsies).  
Medical conditions/diseases present before starting study treatment are only considered 
adverse events if they worsen after starting study treatment (any procedures specified in 
the protocol). Adverse events occurring before starting study treatment but after signing 
the informed consent form will be recorded. Abnormal laboratory values or test results 
constitute adverse events only if they induce clinical signs or symptoms or require 
therapy. 
 Serious adverse event or reaction: Any untoward medical occurrence secondary to 
therapy that: results in death, is immediately life-threatening, requires inpatient 
hospitalization or prolongation of existing hospitalization, results in persistent or 
significant disability / incapacity, or is an important medical event that may jeopardize 
the subject or may require medical intervention to prevent one of the outcomes listed 
above. 
The definition of serious adverse event (experience) also includes important medical 
event. Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is appropriate in other situations, such as important medical events that may not 
be immediately life-threatening or result in death or hospitalization but may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above. These should also usually be considered serious.  
A hospitalization planned before the start of the study agent(s) and/or for a preexisting 
condition that has not worsened does not constitute a serious adverse event (e.g., elective 
hospitalization for breast reconstruction of the ipsilateral breast).  A hospitalization for a 
social reason in the absence of an adverse event also does not meet the criteria for a 
serious adverse event. 
 Unexpected adverse event: An adverse event, which varies in nature, intensity or 
frequency from information on the investigational intervention provided in the 
Investigator’s Brochure, package insert or safety reports. Any adverse event that is not 
included in the informed consent is considered “unexpected”. 
 Expected (known) adverse event: An adverse event, which has been reported in the 
Investigator’s Brochure. An adverse event is considered “expected”, only if it is included 
in the informed consent document as a risk. 
10.4 Relationship 
The relationship of all adverse events and serious adverse events to study medication will be 
assessed by an investigator and assigned as follows: 
 Definitely: An adverse event which has a timely relationship to the administration of the 
investigational drug/agent, follows a known pattern of response, for which no alternative 
cause is present.  
 Probably: An adverse event, which has a timely relationship to the administration of the 
investigational drug/agent, follows a known pattern of response, but for which a potential 
alternative cause may be present.  


 
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 Possibly: An adverse event, which has a timely relationship to the administration of the 
investigational drug/agent, follows no known pattern of response, but a potential 
alternative cause does not exist. 
 Unlikely: An adverse event which does not have a timely relationship to the 
administration of the investigational drug/agent, follows no known pattern of response, 
does not reappear or worsen after re-administration of the investigational drug/agent (if 
applicable), and for which there is evidence that it is related to a cause other than the 
investigational drug/agent. 
 Unrelated: An adverse event, for which there is evidence that it is definitely related to a 
cause other than the investigational drug/agent. In general, there is no timely relationship 
to the administration of the investigational drug/agent, or if there is a timely relationship, 
the event does not follow a known pattern of response, and there is an alternative cause 
10.5 Reporting Procedures 
10.5.1 General 
All adverse events will be captured on the appropriate study-specific case report forms (CRFs) 
through CRMS and REDCap. The Coordinating Center may also periodically request that de-
identified AE logs and deviation logs be submitted via encrypted email, such as for annual 
continuing review. 
10.5.2 Serious Adverse Events 
All serious adverse events, regardless of causality to intervention, will be reported to the PI. 
10.5.3 Institutional Review Board (IRB) 
All adverse events and serious adverse events will be reported to the IRB per current institutional 
standards. If an adverse event requires modification of the informed consent, these modifications 
will be provided to the IRB with the report of the adverse event. If an adverse event requires 


 
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modification to the study protocol, these modifications will be provided to the IRB as soon as is 
possible. 
10.5.4 Reporting to Coordinating Center 
All prompt reporting to the protocol chair must be submitted via encrypted email, preferably 
with subject line starting with “URGENT: J1999”, and must be sent to ALL of the following 
email addresses: 
 jsheng7jhmi.edu  
 HopkinsBreastTrials@jhmi.edu 
 ftoo1@jhmi.edu 
NOTE: Entering data in the study database or eCRFs (e.g., REDCap) is NOT an acceptable 
means of reporting to the sponsor. Likewise, reporting to the sponsor via email does not replace 
the need to enter data in the study database as applicable. 
Do not include patient name, medical record number, or other unneeded patient identifiers in 
reports to the protocol chair. 
 
 
11. DATA AND SAFETY MONITORING 
11.1 Data management 
Participant information relevant to the study will be recorded on a paper case report forms 
customized for this study. Only the PI and authorized staff, according to the list of Authorized 
Study Personnel are entitled to make entries on these forms.  Case report forms will identify 
patients by initials and number only.  Personal patient data will be kept confidential. The PI will 
keep in his/her file a Patient Identification and Enrollment List. Data generated from the case 
report forms will be transferred to a study database on REDCap 
(https://www.jhubc.org/REDCap/) - a secure, web-based application for building and managing 
online surveys and databases.   All information obtained during the study will be regarded as 
confidential.  All study data will be reviewed for completeness and accuracy by the coordinating 
center. The study data will also be periodically reviewed by the SKCCC Clinical Research 
Office (CRO). 
 
11.2 Meetings 
Scheduled meetings will take place as needed with the medical oncology co-investigators and 
study personnel. In addition, separate meetings will be scheduled and include the protocol PI, 
study coordinator(s), data manager(s), collaborators, and biostatistician involved with the 
conduct of the protocol. During these meetings matters related to the following will be discussed: 
safety of protocol participants, validity and integrity of the data, enrollment rate relative to 


 
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expectation, characteristics of participants, retention of participants, adherence to protocol 
(potential or real protocol violations), data completeness, and progress of data for objectives. 
11.3 Monitoring 
This is a project which does not include an investigational drug, agent, or device.  Thus, the 
monitoring will be done by the project personnel. 
The project may be periodically monitored by the SKCCC Clinical Research Review Committee 
(responsible for scientific oversight of studies) and the SKCCC CRO. 
This is a non-therapeutic interventional trial, which is DSMP low risk study under the SKCCC 
Data Safety Monitoring Plan version 6.0 (dated 2/21/2019). The CRO QA Group will perform a 
regulatory and limited subject review during the last year of study with random selection of 10% 
of all subjects. All trial monitoring and reporting will be reviewed annually by the SKCCC 
Safety Monitoring Committee. 
11.4 Data Safety Monitoring Board 
In the event of any questions or matters related to the disclosure policy in publications or in the 
informed consent document, an External Advisory Committee will be assembled, as needed, and 
will be comprised of members who are not affiliated with 1) the Department of Medicine; 2) 
neither the adaptive weight loss study and/or 3) Fitbit. 
 
12. ADMINISTRATIVE PROCEDURES 
12.1 Registration Procedures 
For potential patients of this study, study teams are asked to inform the Coordinating Center of the 
date and time that the patient will need to be registered.   
For non-Hopkins participating sites, all registration materials should be redacted/de-identified and 
received at least 24 hours prior to when eligibility confirmation is needed (submissions after 4pm 
will be considered received the next business day). Submit via encrypted email to the following:  
 Protocol Chair (Dr. Jennifer Sheng): jsheng7@jhmi.edu  
 JH Coordinating Center (HBT and Faith Too):  
o HopkinsBreastTrials@jhmi.edu 
o ftoo1@jhmi.edu  
Subjects will be registered with the study coordinator at the coordinating center (Johns Hopkins) 
once an informed consent form is signed. After eligibility is established, the Coordinating Center 
study coordinator will assign a study number. Subjects will not begin protocol-specified treatment 
until eligibility is confirmed and the patient is assigned a study number. 
Upon review of the registration documents, the Coordinating Center at Johns Hopkins will confirm 
successful registration by return encrypted email to the local study team/designee. 
 


 
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12.2 Protocol Amendments 
Any changes to the protocol will be made in the form of an amendment and must be approved by 
the IRB before implementation. 
Amendments will be distributed by the coordinating center of the lead institution (Johns 
Hopkins) to all affiliate sites upon approval by the Johns Hopkins IRB. Requests or questions 
from sub-sites regarding study documents (such as to obtain a missing document) can be 
submitted through the coordinating center 
12.3 Informed Consent 
The investigator (or his/her designee) will explain to each subject the nature of the project, its 
purpose, the procedures involved, the expected duration, the potential risks and benefits involved 
and any discomfort it may entail.  Each subject will be informed that participation in the project 
is voluntary and that he/she may withdraw from the project at any time and that withdrawal of 
consent will not affect his/her subsequent medical treatment or relationship with the treating 
physician or institution.  The informed consent will be given by means of a standard written 
statement, written in non-technical language, which will be IRB approved.  The subject should 
read and consider the statement before signing and dating it, and will be given a copy of the 
document.  No subject will enter the project before his/her informed consent has been obtained. 
In accordance with the Health Insurance Portability and Accountability Act (HIPAA), the written 
informed consent document will include a subject authorization to release medical information to 
the project sponsor and supporting agencies and/or allow these bodies, a regulatory authority, or 
Institutional Review Board access to subjects’ medical information that includes all hospital 
records relevant to the project, including subjects’ medical history. Our protocol does not contain 
any proprietary (nonpublic) information from an industry sponsor.  
12.4 Ethics and Good Clinical Practice 
This study must be carried out in compliance with the protocol and Good Clinical Practice, as 
described in: 
 ICH Harmonized Tripartite Guidelines for Good Clinical Practice 1996. 
 US 21 Code of Federal Regulations dealing with clinical studies (including parts 50 and 
56 concerning informed consent and IRB regulations). 
 Declaration of Helsinki, concerning medical research in humans (Recommendations 
Guiding Physicians in Biomedical Research Involving Human Subjects, Helsinki 1964, 
amended Tokyo 1975, Venice 1983, Hong Kong 1989, Somerset West 1996). 
The investigator agrees to adhere to the instructions and procedures described in it and thereby to 
adhere to the principles of Good Clinical Practice that it conforms to. 
12.5 Regulatory Authorities 
Information regarding study conduct and progress will be reported to the JHM IRB per the 
current institutional standards. This trial does not use a medication, device, or product which 
requires FDA oversight and no reporting is required with regards to the clinical trial outlined at 


 
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this time. The protocol will be submitted to the NCI for its registration with Clinical Trials 
Registration Program (CTRP).  
12.5.1 JHM Single IRB 
Johns Hopkins Medicine is serving as the single IRB for this study. It is the preference of Johns 
Hopkins Medicine IRB to use the SMART IRB reliance agreement as the basis of reliance. The 
SMART IRB master reliance agreement was created in 2016 to harmonize and streamline the 
IRB review process for multisite studies. It enables reliance on a study-by-study basis, clearly 
defines roles and responsibilities of relying institutions and reviewing IRBs, and eliminates the 
need to sign reliance agreements for each study [e.g., a non-SMART IRB agreement]. 900+ 
institutions have already signed onto this agreement and are actively using it as the basis of 
reliance for multisite projects. Sites that will rely on JHM IRB are still responsible for 
conducting a local context review prior to the start of research at their site and for following any 
local and institutionally required policies as it applies to research at their site [e.g., reporting of 
unanticipated problems]. 
 
13. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
13.1 Study Design 
This is a prospective, non-randomized clinical trial assessing the effects of the addition of 
pharmacotherapy to a behavioral weight loss intervention in overweight/obese breast cancer 
patients on an AI who are unable to attain at least 5% weight loss after 8 weeks of lifestyle 
intervention alone.  
All enrolled patients will participate in a 6-month BWL program. At week 9, patients who 
achieve ≥5% weight loss from baseline will continue with BWL (FAST-BWL). Those failing to 
achieve a minimum of 5% weight loss will receive Contrave in addition to BWL (SLOW-BWL). 
After a 4-week titration of Contrave, SLOW-BWL will have their drug adherence logs and any 
new symptoms reviewed by the Protocol Chair and/or co-investigators. The participants will be 
prescribed the constant dose for 3 months until the end of study (drug will be shipped to patient’s 
home).  
The primary endpoint of this study is the proportion of SLOW-BWL patients who achieve at 
least 5% weight loss of their enrollment baseline weight at 6 months with the addition of 
Contrave to BWL. We anticipate 55% of 55 subjects enrolled will be in the SLOW-BWL group, 
resulting in a sample size of approximately 30 SLOW-BWL women and 25 FAST-BWL women.  
The secondary endpoints include baseline, 2 and 6 months values in all participants for the 
following: cardiometabolic biomarkers (fasting glucose, fasting lipids, fasting insulin, adiponectin 
and leptin levels), genotypes, microbiome composition, body composition, patient-reported 
outcomes (PROs), and physical activities. 
Simon's two-stage minimax design will be used for the SLOW-BWL group. The null hypothesis 
that the true rate of attaining ≥5% weight loss is 10.9%, which is chosen based on the rate of 


 
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women attaining ≥5% weight loss in the self-directed arm in the POWER-remote study.4 In the 
first stage, 15 SLOW-BWL women will be accrued. If there is 1 or fewer woman out of the 15 
women who attain ≥5% weight loss of their baseline weight, the study will be stopped. Otherwise, 
15 additional SLOW-BWL women will be accrued for a total of 30 SLOW-BWL patients. The 
study does not plan to hold enrollment or treatment for the interim analysis. The null hypothesis 
will be rejected if 7 or more women are observed in the 30 patients who attain ≥5% weight loss. 
This design yields a power of 80% at type I error rate of 5% when the true rate of attaining ≥5% 
weight loss of the baseline weight for the SLOW-BWL women is 29%, a clinical meaningful rate 
for the SLOW-BWL women group. 
Our results will inform us of how to better treat obesity in this vulnerable group of breast cancer 
patients. It may allow us to develop larger adaptive trials to assess long term breast cancer and 
non-cancer outcomes of behavioral interventions that incorporate pharmacotherapy. 
Additionally, our results may shed light on other modulators or obesity, such as biomarkers and 
the microbiome, laying foundation to future trials investigating additional interventions in breast 
cancer survivors who struggle with weight loss.  
13.2 Analysis Plans 
Data will be summarized using descriptive statistics (continuous data) and/or contingency tables 
(categorical data) for demographic and baseline characteristics, efficacy measurements at 2 and 6 
months, and safety measurements throughout the study. 
For the primary analysis, the study will be considered successful if there are 7 or more SLOW-
BWL patients who could achieve more than 5% weight loss compared to their baseline weight, 
which implies that the success rate regarding to >=5% weight loss will be significantly higher 
than 10.9%. 
Univariate analysis will be conducted to compare outcomes at different time points including 
baseline, 2 months and 6 months, and to compare outcomes from different groups including 
SLOW-BWL patients who attain ≥5% weight loss or <5% weight loss of their enrollment 
baseline weight at 6 months and FASE-BWL patients. Wilcoxon rank sum and Wilcoxon sign 
rank tests will be conducted when appropriate. Student’s t-test will also be performed when the 
outcomes are normally distributed after necessary data transformation. Moreover, mixed effect 
regression analysis will be conducted to evaluate the longitudinal trend in the outcomes at 
different time points.  
Furthermore, multivariate logistic regression analysis will be conducted to evaluate the effect of 
the baseline characteristics on attaining ≥5% weight loss of the baseline weight at 2 months 
among FAST- and SLOW-BWL patients, and to evaluate the effect of the baseline 
characteristics and the weight loss at 2 months on attaining ≥5% weight loss of the baseline 
weight at 6 months for SLOW-BWL patients.  


 
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The primary analysis dataset will be based on the intent-to-treat population. Analysis based on 
the per-protocol population will also be conducted as exploratory analysis. Missing data will be 
handled by multiple imputation and sensitivity analysis.   
13.3 Early Stopping 
Following the Simon’s two-stage design, the study will be stopped early for futility if there is 1 
or fewer woman who attain ≥5% weight loss in the first 15 SLOW-BWL women. 
13.4 Analysis Populations 
Intent to treat (ITT) population:  
The ITT population comprises all SLOW-BWL women who receive any Contrave. 
Women who discontinue or are lost to follow-up prior to evaluation of the primary 
endpoint will be considered to have not achieved ≥5% weight loss, and will not be 
replaced. 
Safety population:   
The safety population comprises patients who enroll in the study and participate in BWL 
alone or BWL + Contrave. 
Per-protocol population:  
The per-protocol population comprises all patients who were compliant with the study. 
 
 


 
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71.  Han YH, Buffolo M, Pires KM, Pei S, Scherer PE, Boudina S. Adipocyte-Specific Deletion of 
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81.  Gadde KM. Current pharmacotherapy for obesity: extrapolation of clinical trials data to 
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82.  Yanovski SZ, Yanovski JA. Long-term Drug Treatment for Obesity: A Systematic and Clinical 
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86.  Golden A. Current pharmacotherapies for obesity: A practical perspective. J Am Assoc Nurse 
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95.  Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight 
loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, 
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102.  Rose M, Bjorner JB, Becker J, Fries JF, Ware JE. Evaluation of a preliminary physical 
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103.  Amtmann D, Cook KF, Jensen MP, et al. Development of a PROMIS item bank to 
measure pain interference. Pain 2010;150(1):173–82.  
104.  Garcia SF, Cella D, Clauser SB, et al. Standardizing patient-reported outcomes 
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105.  Fallowfield LJ, Bliss JM, Porter LS, et al. Quality of life in the intergroup exemestane 
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106.  Buysse DJ, Yu L, Moul DE, et al. Development and validation of patient-reported 
outcome measures for sleep disturbance and sleep-related impairments. Sleep 
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107.  Lavsa SM, Holzworth A, Ansani NT. Selection of a validated scale for measuring 
medication adherence. J Am Pharm Assoc JAPhA 2011;51(1):90–4.  
108.  Fruit & Vegetable Screeners in the Eating at America’s Table Study (EATS): Instruments 
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109.  Strath SJ, Swartz AM, Bassett DR, O’Brien WL, King GA, Ainsworth BE. Evaluation of 
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110.  Ainsworth BE, Bassett DR, Strath SJ, et al. Comparison of three methods for measuring 
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111.  Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine 
roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 
2010;42(7):1409–26.  
 
 
 


 
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APPENDICES 
A:  ECOG Performance Scale 
B:  Lifestyle Guidelines Handout 
C:  Symptom checklist  
D: Aim for a Healthy Weight Brochure 
E:  PRO Questionnaire  
F: Score Interpretation 
G:  Drug diary 
 
 
 


 
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APPENDIX A:  ECOG Performance Status Scale 
 
  
Score 
Definition 
0 
Asymptomatic 
1 
Symptomatic, fully ambulatory 
2 
Symptomatic, in bed less than 50% of day 
3 
Symptomatic, in bed more than 50% of day,  
but not bedridden 
4 
Bedridden 
 
 
 
 
 


 
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APPENDIX B:  Lifestyle Guidelines Handout  
Goal: Lose 5% or more of your body weight at 2 months and maintain weight loss  
1.  Keep calories in moderation* 
To lose weight, if you currently weigh: 
Less than 170 pounds: Consume approximately 1200 calories each day  
171-220 pounds: Consume approximately 1500 calories each day  
221-270 pounds: Consume approximately 1800 calories each day 
More than 270 pounds: Consume approximately 2200 calories each day 
 
*Calorie levels: There is not one specific number that’s right for you all the time. Your calorie 
need may change depending on exercise, lifestyle and where you are in the weight loss process. 
2.  Exercise regularly 
We recommend moderate intensity aerobic exercise 30 – 60 minutes for 5 – 7 days per week in 
bouts of at least 10 minutes. Start with 60 minutes per week and gradually increase each week so 
that at Week 21, you are reaching 180 minutes of aerobic exercise per week.  
3. Weigh yourself weekly when trying to lose weight and daily to maintain weight loss.  
When you do weigh yourself, enter it into the website.  Be sure to do this at least once per week. 
4. Keep track of your eating and exercise.  
Daily track your food, beverage and exercise type and minutes and Log on to the Fitbit website 
at least once per week and enter all your tracking information. We understand that it may be 
challenging to track your food over a 24 hours period every day of the week. We encourage you 
to log 24 hours of what you eat at least 4 of 7 days of the week.  
Fitbit device for monitoring physical activity (wear this on your non-dominant hand for a 
minimum of 4 of 7 days with 10 hours per day) 
5.  Be an active study participant 
Attend data collection visits and complete surveys at week 8 and 6 month follow-up. Keep all 
appointments with your Coach and complete Learning Focuses before calls. 
Other recommended guidelines 
Follow one of two eating styles: 
1) The DASH diet 
 Eat 7-12 servings of fruits and vegetables every day 
 Eat 2-3 servings of low-fat dairy foods every day 
 Eat 25% or less of your total calories from fat 
2) The Mediterranean diet 


 
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3)  
 Daily consumption of vegetables, fruits, whole grains and healthy fats 
 Weekly intake of fish, poultry, beans and eggs 
 Moderate portions of dairy products 
 Limited intake of red meat and alcohol 
Eat a low-sodium diet 
 Eat 2400 mg or less of sodium each day 
Limit alcohol intake 
 Women: Drink no more than one drink per day 
 Men: Drink no more than two drinks per day 
1 drink=12 ounces beer, 5 ounces wine, or 1 jigger (1 ½ ounce) of 80-proof liquor 
 
 


 
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APPENDIX C:  Weekly weight and symptom survey  
 
During the behavioral intervention, coaches call patients weekly the first 3 months, followed by 
monthly for months 4-6. Patients will receive a REDCap survey on a weekly basis with the 
following question: 
1) What is your weight this week? ___________ 
*If patients have not completed this survey before the call with the coach, the coach may enter 
the data that is conveyed verbally.  
 
During months 3-6, ALL study participants will continue with weekly survey, in addition to a 
question about any new symptoms: 
2) During the past 7 days, have you experienced any new symptoms (such as abdominal 
pain, anxiety, constipation, diarrhea, dizziness, dry mouth, fatigue, gastroenteritis, 
headache, hot flush, insomnia, nausea, tremor, vomiting etc.)? 
__________________________________________________________________ 
*If patients have not completed this survey before the call with the coach, the coach may enter 
the data that is conveyed verbally. 
**The coordinator will review all new symptom entries in the REDCap survey on a weekly basis, 
and new symptoms will be reported to the PI for further evaluation.  
 
 


 
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APPENDIX D: Aim for a Healthy Weight Brochure  
 
Participants who are not eligible for the study at the screening visit will be provided the NHLBI 
publication “Aim for A Healthy Weight.” 
The publication is publically available and will be downloaded from the National Institutes of 
Health’s website to be given to study participants: 
http://www.nhlbi.nih.gov/health/public/heart/obesity/aim_hwt.pdf  
 
 
 


 
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APPENDIX E:  PRO Questionnaire  
 
The following represents the questions to be asked in the REDCap survey. 
 
CLINICAL AND DEMOGRAPHIC INFROMATION  
 
I. Demographics: 
a. What is your date of birth? 
b. What is your age? 
c. Are you Hispanic or Latino?   
i. Yes 
ii. No 
d. What is your race? 
 
 
i. White/Caucasian 
ii. Black or African American  
iii. Asian 
iv. Native Hawaiian or Pacific Islander  
v.  American Indian or Alaska Native  
vi. Other, _________________ 
 
II. Past Medical/social/family history 
 
1. Have you had a menstrual period in the past 12 months?  
a. Yes 
b. No 
 
2. If you have not had a menstrual period in the last 12 months, at what age did you stop 
having periods? (free text)  
 
3. During the past year how many alcoholic beverages did you have? 
a. Never or less than 1 per month  
b. 1-3 per month  
c. 1 per week  
d. 2-4 per week  
e. 5-6 per week  
f. 1 per day  
g. 2-3 per day  
h. 4-5 per day  


 
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i. More than 5 per day 
 
4. Have you ever smoked? 
a. Yes 
b. No 
 
5. If you have ever smoked, please indicate how many cigarettes you smoked when you 
were smoking: 
a. Never smoked 
b. Less than one-half pack per day 
c. One-half to one pack per day 
d. Two packs per day 
e. Three packs per day 
f. More than three packs per day 
 
6. If you have ever smoked, please indicate how many years you smoked:  
a. One year 
b. 2-5 years 
c. 6-10 years 
d. 11-15 years 
e. 16-20 years 
f. 21-25 years 
g. 26-30 years  
h. 31-35 years 
i. >35 years 
 
III. Medications 
 
1. Which of the following medications are you taking? (Select all that apply) 
a.   Tamoxifen 
b.   Raloxifene (Evista) 
c.   Anastrozole (Arimidex) 
a. Letrozole (Femara) 
b. Exemestane (Aromasin) 
c. Goserelin (Zoladex) 
d. Leuprolide (Lupron) 
  
 
 


 
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IV. Patient Reported Outcomes (PROs) – Sleep 
 
In the past month…  
1. 
During the past month, what time have you usually gone to bed at night? 
                                             BED TIME ___________ 
2. 
During the past month, how long (in minutes) has it usually taken you to fall asleep each night? 
                                             NUMBER OF MINUTES __________              
3. 
During the past month, what time have you usually gotten up in the morning? 
                                             GETTING UP TIME ___________              
4. 
During the past month, how many hours of actual sleep did you get at night?  (This may be 
different than the number of hours you spent in bed.) 
                                             HOURS OF SLEEP PER NIGHT __________                            
 
For each of the remaining questions, check the one best response.  Please answer all questions. 
 
5. 
During the past month, how often have you had trouble sleeping because you . . . 
a) 
Cannot get to sleep within 30 minutes 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
b) 
Wake up in the middle of the night or early morning 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
c) 
Have to get up to use the bathroom 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
d) 
Cannot breathe comfortably 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
e) 
Cough or snore loudly 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 


 
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f) 
Feel too cold 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
g) 
Feel too hot 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
h) 
Had bad dreams 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
i) 
Have pain 
Not during the 
Less than 
Once or twice 
Three or more 
  
 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
 
j) 
Other reason(s), please describe__________________________________________ 
__________________________________________________________________________ 
How often during the past month have you had trouble sleeping because of this? 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
 
7. 
During the past month, how would you rate your sleep quality overall? 
Very good   ____________ 
Fairly good ____________ 
Fairly bad  ____________ 
Very bad    ____________ 
8.  
During the past month, how often have you taken medicine to help you sleep (prescribed or "over 
the counter")? 
Not during the 
Less than 
Once or twice 
Three or more 
past month_____ 
once a week_____ 
a week_____ 
times a week_____ 
 
8. 
During the past month, how often have you had trouble staying awake while driving, eating meals, 
or engaging in social activity? 


 
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Not during the 
Less than 
Once or twice 
  Three or more 
past month_____ 
once a week_____ 
a week_____ 
  times a week_____ 
 
9. 
During the past month, how much of a problem has it been for you to keep up enough enthusiasm 
to get things done? 
No problem at all 
__________ 
Only a very slight problem 
__________ 
Somewhat of a problem 
__________ 
A very big problem 
__________ 
 
V. Patient Reported Outcomes (PROs) – Physical Function 
 
1. Does your health now limit you in doing vigorous activities such as running, lifting heavy 
objects, participating in strenuous sports? 
a. Not at all 
b. Very little 
c. Somewhat 
d. Quite a lot 
e. Cannot do 
 
2. Does your health now limit you in walking more than a mile? 
a. Not at all 
b. Very little 
c. Somewhat 
d. Quite a lot 
e. Cannot do 
 
3. Does your health now limit you in climbing one flight of stairs? 
a. Not at all 
b. Very little 
c. Somewhat 
d. Quite a lot 
e. Cannot do 
 
4. Does your health now limit you in lifting or carrying groceries? 
a. Not at all 
b. Very little 
c. Somewhat 
d. Quite a lot 


 
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e. Cannot do 
 
5. Does your health now limit you in bending, kneeling or stooping? 
a. Not at all 
b. Very little 
c. Somewhat 
d. Quite a lot 
e. Cannot do 
 
6. Are you able to do chores such as vacuuming or yard work? 
a. Without any difficulty 
b. With a little difficulty 
c. With some difficulty 
d. With much difficulty 
e. Unable to do 
 
7. Are you able to dress yourself, including tying shoelaces and doing buttons? 
a. Without any difficulty 
b. With a little difficulty 
c. With some difficulty 
d. With much difficulty 
e. Unable to do 
 
8. Are you able to shampoo your hair? 
a. Without any difficulty 
b. With a little difficulty 
c. With some difficulty 
d. With much difficulty 
e. Unable to do 
9. Are you able to wash and dry your body? 
a. Without any difficulty 
b. With a little difficulty 
c. With some difficulty 
d. With much difficulty 
e. Unable to do 
 
10. Are you able to get on and off the toilet? 
a. Without any difficulty 
b. With a little difficulty 
c. With some difficulty 
d. With much difficulty 
e. Unable to do 
 
VI. Patient Reported Outcomes (PROs) - Anxiety 


 
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In the past 7 days…… 
 
1. I felt fearful 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
2. I felt anxious 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
3. I felt worried 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
4. I found it hard to focus on anything other than my anxiety 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
5. I felt nervous 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
6. I felt uneasy 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 


 
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7. I felt tense 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
VII. 
Patient Reported Outcomes (PROs) - Depression 
 
In the past 7 days…. 
 
1. I felt worthless 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
2. I felt that I had nothing to look forward to 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
3. I felt helpless 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
4. I felt sad 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
5. I felt like a failure 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 


 
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e. Always 
 
6. I felt depressed 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
7. I felt unhappy 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
8. I felt hopeless 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
VIII. Patient Reported Outcomes (PROs) - Pain 
 
In the past 7 days….. 
 
1. How much did pain interfere with your enjoyment of life?  
a. Not at all 
b. A little bit 
c. Somewhat 
d. Quite a bit 
e. Very much 
2. How much did pain interfere with your ability to concentrate? 
a. Not at all 
b. A little bit 
c. Somewhat 
d. Quite a bit 
e. Very much 
 
3. How much did pain interfere with your day to day activities?  
a. Not at all 
b. A little bit 
c. Somewhat 


 
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d. Quite a bit 
e. Very much 
 
4. How much did pain interfere with your enjoyment of recreational activities? 
a. Not at all 
b. A little bit 
c. Somewhat 
d. Quite a bit 
e. Very much 
 
5. How much did pain interfere with your doing tasks away from home (eg. getting 
groceries, running errands)? 
a. Not at all 
b. A little bit 
c. Somewhat 
d. Quite a bit 
e. Very much 
 
6. How often did pain keep you from socializing with others?  
a. Never 
b. Rarely 
c. Sometimes 
d. Often 
e. Always 
 
IX. Patient Reported Outcomes (PROs) - Fatigue 
 
In the past 7 days….. 
 
1. How often did you feel tired?  
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
2. How often did you experience extreme exhaustion? 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
3. How often did you run out of energy? 
a. Never 


 
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b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
4. How often did your fatigue limit you at work (include work at home)? 
a.   Never 
b.   Rarely 
c.   Sometimes  
d.   Often 
e.   Always 
 
5. How often were you too tired to think clearly?  
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
6. How often were you too tired to take a bath or shower? 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
7. How often did you have enough energy to exercise strenuously? 
a. Never 
b. Rarely 
c. Sometimes  
d. Often 
e. Always 
 
X. Patient Reported Outcomes (PROs) – MOS Sexual Function Scale 
 
 
Lack of sexual 
interest 
Not a 
problem 
Little of a 
problem 
Somewhat of a 
problem 
Very much of 
a problem 
Not 
applicable 
1 
2 
3 
4 
5 


 
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Unable to relax and 
enjoy sex 
Not a 
problem 
Little of a 
problem 
Somewhat of a 
problem 
Very much of 
a problem 
Not 
applicable 
1 
2 
3 
4 
5 
Difficulty in 
becoming sexually 
aroused 
Not a 
problem 
Little of a 
problem 
Somewhat of a 
problem 
Very much of 
a problem 
Not 
applicable 
1 
2 
3 
4 
5 
Difficulty in having 
an orgasm 
Not a 
problem 
Little of a 
problem 
Somewhat of a 
problem 
Very much of 
a problem 
Not 
applicable 
1 
2 
3 
4 
5 
 
XI. Patient Reported Outcomes (PROs) – Endocrine Symptoms FACT-ES 
 
Please mark one number per line to indicate your response as it applies to the past 7 days. 
 
 
Not 
at all 
A little 
bit 
Some
-what 
Quite 
a bit 
Very 
much 
I have hot flashes
 ................................................................................... 
0 
1 
2 
3 
4 
I have cold sweats
 ................................................................................... 
0 
1 
2 
3 
4 
I have night sweats
 ................................................................................... 
0 
1 
2 
3 
4 
I have vaginal discharge
 ................................................................................... 
0 
1 
2 
3 
4 


 
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I have vaginal itching/irritation
 ................................................................................... 
0 
1 
2 
3 
4 
I have vaginal bleeding or spotting
 ................................................................................... 
0 
1 
2 
3 
4 
I have vaginal dryness
 ................................................................................... 
0 
1 
2 
3 
4 
I have pain or discomfort with intercourse
 ................................................................................... 
0 
1 
2 
3 
4 
I have lost interest in sex
 ................................................................................... 
0 
1 
2 
3 
4 
I have gained weight
 ................................................................................... 
0 
1 
2 
3 
4 
I feel lightheaded (dizzy)
 ................................................................................... 
0 
1 
2 
3 
4 
I have been vomiting
 ................................................................................... 
0 
1 
2 
3 
4 
I have diarrhea (diarrhea)
 ................................................................................... 
0 
1 
2 
3 
4 
I get headaches
 ................................................................................... 
0 
1 
2 
3 
4 
I feel bloated
 ................................................................................... 
0 
1 
2 
3 
4 
I have breast sensitivity/tenderness
 ................................................................................... 
0 
1 
2 
3 
4 


 
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I have mood swings
 ................................................................................... 
0 
1 
2 
3 
4 
I am irritable
 ................................................................................... 
0 
1 
2 
3 
4 
I have pain in my joints
 ................................................................................... 
0 
1 
2 
3 
4 
XII. 
Godin Leisure-Time Exercise questionnaire 
Please indicate the average amount of exercise you did in the last 7 days.  
When answering these questions, please:  
● note that the main difference between the 3 questions below is the intensity of the exercise.  
● if you did not do any exercise in one of the categories, please write in “0”.  
 
Considering a typical week (7 days), how many times on average did you do the 
following kinds of exercise for more than 15 minutes during your free time?  
 
For example, if you did fast walking for a total of 60 minutes over the past week, 
you would write 4.  
 
 
Times Per Week 
 
STRENUOUS EXERCISE 
 
What is strenuous? HEART BEATS RAPIDLY, SWEATING 
(e.g. running, jogging, hockey, soccer, squash, cross country skiing, vigorous 
swimming, vigorous long distance bicycling, vigorous aerobic dance classes) 
 
Times Per Week 
 
MODERATE EXERCISE 
What is moderate? NOT EXHAUSTING, LIGHT PERSPIRATION 
(e.g. fast walking, easy bicycling, baseball, tennis, volleyball, easy swimming) 
 
Times Per Week 
 
MILD EXERCISE 
What is mild? MINIMAL EFFORT, NO PERSPIRATION


 
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(e.g. easy walking, yoga, archery, bowling, golf)
 
XIII. Nutritional survey 
The following represents the questions to be incorporated in the PatientViewPoint online 
modules, as taken from the National Institutes of Health’s “Eating at America’s Table Study” 
(quick food scan). 


 
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APPENDIX F: Score Interpretation  
NOTE:  Please see below an example of the information to be provided to the participant upon 
completion of the questionnaires. This information will be also available to the providers to 
discuss with participants during their clinic visit. 
The reports produced by the system will highlight scores that are potential 'problems' because 
they represent either particularly poor health, quality of life below average, or significant 
worsening from the last time point, as follows: 
Sleep Disturbance, Physical Function, Anxiety, Depression, Pain Impact, and Fatigue:   
 Higher scores represent more of what is being measured (e.g., higher scores indicate 
better physical function and worse fatigue).   
 A score of 30-70 is considered within the expected range of an average population of 
patients.   
 Highlighted scores are either outside of that range (less than 30 for physical function; 
greater than 70 for all others) or are a significant change from previous answers.   
Sexual Function: 
 Higher scores indicate more problems with sexual function. 
 A score of less than 40 is considered to be within the expected range of an average 
population of patients.   
 Highlighted scores are above that average range (greater than 40) or a significant increase 
from previous answers. 
Endocrine Symptoms:  
 Higher scores indicate better quality of life.  
 A score of 41.3 - 76 is considered to be within the expected range for an average 
population of women.   
 Highlighted scores are below that average range (less than 41.3) or a significant decrease 
from previous answers.   
 
Godin Leisure-Time Exercise questionnaire 
 For the first question, weekly frequencies of strenuous, moderate, and light activities are 
multiplied by nine, five, and three, respectively.  
 Total weekly leisure activity is calculated in arbitrary units by summing the products of the 
separate components, as shown in the following formula: Weekly leisure activity score = 
(9  Strenuous) + (5  Moderate) + (3  Light).  
 For example: Strenuous = 3 times/wk. Moderate = 6 times/wk, and Light = 14 times/wk. 
Then, the total leisure activity score = (9  3) + (5  6) + (3  14) = 27 + 30 + 42 = 99.  
 Godin scale score of ≥24 is active, 14-23 is moderately active, and <14 is insufficient active 
or sedentary.  


 
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Statistical Considerations 
Sleep Disturbance, Physical Function, Anxiety, Depression, Pain Impact, and Fatigue:   
 Surveys were validated in the general population.   
 All of these domains are mapped to a mean score of 50, with a standard deviation of 10.   
 Highlighted scores represent a score more than 2 standard deviations from the mean (20 
points) or a worsening of at least half a standard deviation (5 points).   
Sexual Function:  
 This survey was validated in patients with major medical problems with and without 
depression, and patients without medical problems but with depression.   
 For this population, the mean sexual problem scores ranged from 24.48 – 43.5, with a 
standard deviation of 32.  
 Highlighted scores represent a score that is worse than the average scores among an ill 
population (40 points) or a worsening of at least half a standard deviation (16 points).  
 
Endocrine Symptoms:  
 This survey was validated in female breast cancer patients undergoing a variety of 
hormone therapies as well as normal controls.   
 This survey is mapped to a mean score of 59.7, which is the total group mean from the 
validated population, with a standard deviation of 9.2.   
 Highlighted scores represent a score that is two standard deviations away from the mean 
(41.3 points) or a worsening of at least half a standard deviation (4.6 points).   
 
 
 


 
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APPENDIX G:   
Drug Diary 
Contrave should not be taken with a high-fat meal.  
Check boxes if the drug is taken and list any side effects you 
experience. Email you drug diary weekly to ANEW@jhmi.edu. 
WEEK 1: Take one pill in the morning. 
 
WEEK 2: Take one pill in the morning and one in the evening. 
 
WEEK 3: Take 2 pills in the morning and 1 pill in the evening. 
 
WEEK 4: Take 2 pills in the morning and 2 pills in the evening. 
Contrave 
Day 
Notes 
Morning 
dose 
#1 tablet 
DO NOT 
TAKE 
Evening 
dose
Yes
No
Week 1 
 
1 
 
 
 
2
3
4
5
6 
 
 
 
7
Contrave 
Day 
Notes 
Morning 
dose 
#1 tablet
Evening 
dose 
#1 tablet
Yes
No
Yes
No
Week 2 
 
1
2 
 
3
4
5
6
7
Contrave 
Day 
Notes 
Morning 
dose 
#2 tablets
Evening 
dose 
#1 tablet
Yes
No
Yes
No
Week 3 
 
1
2
3
4
5
6
7


 
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Contrave 
Day 
Notes 
Morning 
dose  
#2 tablets
Evening 
dose 
#2 tablets
Yes
No
Yes
No
Week 4 
and 
onward 
 
1 
 
2
3
4
5
6
7