A Feasibility Pilot Trial Evaluating Caloric Restriction for Oncology Research in Early Stage Breast Cancer Patients
Phase: NA
Conditions: Ductal Breast Carcinoma in Situ, Invasive Ductal Breast Carcinoma, Invasive Lobular Breast Carcinoma, Lobular Breast Carcinoma in Situ, Recurrent Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
1 
THOMAS JEFFERSON UNIVERSITY 
Kimmel Cancer Center 
 
CAREFOR Study: A Feasibility Pilot Trial Evaluating Caloric Restriction for 
Oncology Research in Early Stage breast cancer patients  
 
 
Principal Investigator: 
Nicole Simone, MD 
 
 
215-955-6702 
Co-Investigator(s): 
 
 
 
 
 
 
 
 
 
 
  
  
 
Non-consenting  
Co-Investigator(s): 
 
 
 
Funding Sponsor: 
Ladies of Port Richmond Pilot Award 
 
Version: 
Date: 
Initial, 1  
11/7/12 
AMDT. 2 
4/3/13 
3.0 
12/3/2013 
4.0 
5/21/2014 
4.1 
1/9/2015 
4.2 
1/4/2016 
 
CONFIDENTIAL 
This document is confidential and the property of THOMAS JEFFERSON UNIVERSITY.  No part of it may 
be transmitted, reproduced, published, or used by other persons without prior written authorization from 
the study sponsor. 
 
 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
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Table of Contents 
1 
INTRODUCTION .............................................................................................................................................. 9 
 
Specific Aims and Hypothesis .................................................................................................................... 9 
1.1
 
Background and Rationale .......................................................................................................................... 9 
1.2
 
Study Therapy .......................................................................................................................................... 11 
1.3
 
Preclinical Data ........................................................................................................................................ 11 
1.4
 
Clinical Data to Date ................................................................................................................................ 14 
1.5
 
Dose Rationale and Risk/Benefits ............................................................................................................ 14 
1.6
2 
STUDY OBJECTIVES .................................................................................................................................... 15 
 
Primary Objective ..................................................................................................................................... 15 
2.1
 
Secondary Objective ................................................................................................................................. 15 
2.2
3 
STUDY DESIGN .............................................................................................................................................. 16 
 
General Design ......................................................................................................................................... 16 
3.1
 
Primary Study Endpoints .......................................................................................................................... 17 
3.2
 
Secondary Study Endpoints ...................................................................................................................... 18 
3.3
 
Primary Safety Endpoints ......................................................................................................................... 19 
3.4
4 
SUBJECT SELECTION AND WITHDRAWAL.......................................................................................... 19 
 
Inclusion Criteria ...................................................................................................................................... 19 
4.1
 
Exclusion Criteria ..................................................................................................................................... 20 
4.2
 
Gender/Minority/Pediatric Inclusion for Research ................................................................................... 21 
4.3
 
Subject Recruitment and Screening .......................................................................................................... 21 
4.4
 
Early Withdrawal of Subjects ................................................................................................................... 22 
4.5
 
When and How to Withdraw Subjects ............................................................................................... 22 
4.5.1
 
Data Collection and Follow-up for Withdrawn Subjects .................................................................. 22 
4.5.2
5 
STUDY DRUG/THERAPY ............................................................................................................................. 23 
 
Description ............................................................................................................................................... 23 
5.1
 
Treatment Regimen .................................................................................................................................. 23 
5.2
 
Prior to lumpectomy: ........................................................................... Error! Bookmark not defined. 
5.2.1
 
Prior to Radiation: ............................................................................................................................ 23 
5.2.2
 
Risks of Caloric Restriction ...................................................................................................................... 23 
5.3
 
Method for Assigning Subjects to Treatment Groups .............................................................................. 24 
5.4
 
Preparation and Administration of Study Drug/Therapy .......................................................................... 24 
5.5
 
Compliance Monitoring ............................................................................................................................ 24 
5.6
 
Prior and Concomitant Therapy................................................................................................................ 25 
5.7
6 
STUDY PROCEDURES .................................................................................................................................. 25 
 
Treatment Overview ................................................................................................................................. 25 
6.1
 
Study Visit Schedule ................................................................................................................................ 25 
6.2
 
Screening ........................................................................................................................................... 25 
6.2.1
 
Phase I—Pre-treatment ..................................................................................................................... 25 
6.2.2
 
Phase II—Visits During Radiation Treatment ................................................................................... 26 
6.2.3
 
Phase III—Post Radiation Treatment ................................................................................................ 26 
6.2.4
 
Study Flowchart ........................................................................................................................................ 27 
6.3
 
Radiation Treatment ................................................................................................................................. 28 
6.4
 
Dose Specifications ........................................................................................................................... 28 
6.4.1
 
Technical Factors .............................................................................................................................. 28 
6.4.2
 
Localization, Simulation, and Immobilization ................................................................................... 29 
6.4.3
 
Treatment Planning/Target Volumes ................................................................................................. 29 
6.4.4
 
Treatment Verification ............................................................................................................................. 30 
6.5

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
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Before first treatment: ....................................................................................................................... 30 
6.5.1
 
Subsequent images or films: .............................................................................................................. 30 
6.5.2
 
Radiation Therapy Adverse Events .......................................................................................................... 30 
6.6
7 
STATISTICAL PLAN ..................................................................................................................................... 30 
 
Sample Size Determination ...................................................................................................................... 30 
7.1
 
Statistical Methods ................................................................................................................................... 31 
7.2
 
Subject Population(s) for Analysis ........................................................................................................... 31 
7.3
8 
SAFETY AND ADVERSE EVENTS ............................................................................................................. 31 
 
Definitions ................................................................................................................................................ 31 
8.1
 
Adverse Event .................................................................................................................................... 31 
8.1.1
 
Serious Adverse Event ....................................................................................................................... 32 
8.1.2
 
Adverse Event Reporting Period ....................................................................................................... 32 
8.1.3
 
Preexisting Condition ........................................................................................................................ 32 
8.1.4
 
General Physical Examination Findings ........................................................................................... 32 
8.1.5
 
Post-study Adverse Event .................................................................................................................. 32 
8.1.6
 
Abnormal Laboratory Values ............................................................................................................ 33 
8.1.7
 
Hospitalization, Prolonged Hospitalization or Surgery .................................................................... 33 
8.1.8
 
Recording of Adverse Events ................................................................................................................... 33 
8.2
 
Unblinding Procedures ............................................................................................................................. 34 
8.3
 
Stopping Rules.......................................................................................................................................... 34 
8.4
 
Data and Safety Monitoring Plan ............................................................................................................. 34 
8.5
 
Medical Monitoring and AE/SAE Reporting ..................................................................................... 34 
8.5.1
 
Data and Safety Monitoring Committee ............................................................................................ 35 
8.5.2
9 
DATA HANDLING AND RECORD KEEPING .......................................................................................... 36 
 
Confidentiality .......................................................................................................................................... 36 
9.1
 
Source Documents .................................................................................................................................... 36 
9.2
 
Case Report Forms ................................................................................................................................... 37 
9.3
 
Records Retention .................................................................................................................................... 37 
9.4
10 
STUDY MONITORING, AUDITING, AND INSPECTING ....................................................................... 37 
 
Study Monitoring Plan.............................................................................................................................. 37 
10.1
 
Auditing and Inspecting ............................................................................................................................ 37 
10.2
 
Independent External and Internal Audits ......................................................................................... 37 
10.2.1
11 
ETHICAL CONSIDERATIONS .................................................................................................................... 38 
12 
STUDY FINANCES ......................................................................................................................................... 38 
 
Funding Source ......................................................................................................................................... 38 
12.1
 
Conflict of Interest .................................................................................................................................... 39 
12.2
13 
PUBLICATION PLAN .................................................................................................................................... 39 
14 
SPECIMEN BANKING................................................................................................................................... 39 
15 
REFERENCES ................................................................................................................................................. 39 
16 
APPENDICES .................................................................................................................................................. 41 
 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
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List of Abbreviations 
 
BrCa: breast cancer 
CR: caloric restriction 
RT: radiation 
IGF: insulin-like growth factor  
NCI: National Cancer Institute 
BCT: Breast conserving therapy 
TJUH: Thomas Jefferson University Hospital 
 
 
 
 
 
 
 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
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Study Summary 
Title 
CAREFOR study: A feasibility pilot trial evaluating caloric restriction for 
oncology research in early stage breast cancer patients 
Short Title 
CAREFOR Study: Caloric Restriction for Oncology Research 
Phase 
Pilot Trial 
Methodology/ 
Study Design 
Single site (early stage breast cancer), Pilot study with one arm 
Study Duration 
5 years 
Study Center(s) Thomas Jefferson University Hospital 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
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Objectives 
The primary objectives are as follows: 
The study will be conducted in two phases. The first phase will enroll 
40 patients. At the end of it, we will determine adherence to CR. We 
will then proceed to the second phase which will enroll an additional 
50 patients, for a total study sample size of 90, and at its end we will 
assess toxicity, as well as potential predictors of it. 
Phase 1: Investigate the feasibility of a clinical trial administering ionizing 
radiation with concurrent CR for the treatment of breast cancer. True 
adherence will be defined as a successful reduction of 25% of total calories 
based on diet journals in at least 80% of the logged events. 
Phase 2: Acute skin toxicity as defined by the National Cancer 
Institute Common Toxicity Criteria (NCI CTCv.4 for skin reaction, pain 
and the occurrence of moist desquamation) will be followed to ensure 
noninferiority as compared with historical controls. 
The secondary objectives are as follows: 
Investigate measurable changes of patient characteristics and tissue and 
serum from fasting/CR conditions to determine a metric for evaluating this 
treatment in future studies. 
 
Weight: Weight will be monitored by body mass index, at baseline, week 
1, 3, 5 and 7, conclusion and 4 weeks after diet is complete. Body fat 
measurements via calipers and bioimpedance which will be done at 
baseline, conclusion and 4 weeks after diet is completed.  Vital signs will 
be monitored weekly. 
 
Serum:  
 
At initiation of diet, conclusion of diet and 4 weeks after diet is 
complete, fasting labs will be drawn: 
 
Clinical Lab: CBC, basic metabolic panel, hemoglobin A1C, 
triglycerides, insulin, IGF-1, erythrocyte sedimentation rate (ESR), 
adiponectin, leptin and estradiol 
 
Other Serum Markers:  IGF-1R, IRS-1, proteomic and/or genomic 
analysis 
 
At week 5: a fasting insulin level will be evaluated. 
 
Psycho-social evaluation: Patients will have psycho-social evaluation 
using the FACT-B test and the PROMIS cancer fatigue short form at 
baseline, week 5, conclusion and 4 weeks after conclusion. 
 
Outcomes: Local recurrence, progression free survival, distant 
metastases and overall survival will be assessed through patient records 
after study has been completed. 
 
Toxicity: acute skin reaction or pain using the National Cancer Institute 
Common Toxicity Criteria (NCI CTC) version 4.0 scale22 will be 
assessed. Number of patients experiencing toxicity and time to 
occurrence of toxicity will be recorded. This toxicity will be compared to 
historical controls from TJUH who have also been treated for a 6 – 6.5 
week course of radiation.  

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
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Number of 
Subjects 
90 
Diagnosis and 
Main Inclusion 
Criteria 
Patients with DCIS or invasive breast cancer who will receive radiation and 
are appropriate candidates for breast conservation to be treated to the whole 
breast 
 
Study Therapy, 
Dose, Route, 
Regimen 
Radiation and Caloric Restriction: a 25% reduction in total caloric intake 
Duration of 
administration 
and follow-up 
Caloric Restriction for 10weeks (2weeks minimum prior to radiation, during 6-
6.5 weeks of radiation and 2 weeks minimum after for a total of at least 
10weeks) with a follow up visit 4 weeks after treatment completion. 
Reference 
therapy 
Patients acute toxicity on this trial will be compared with historic controls of 
other patients who received 6-6.5 weeks of radiation at Bodine Cancer Center  
Statistical 
Methodology 
The study will enroll a total of 90 patients. Phase 1: With a sample size of 40, 
the study has 83% power to establish that adherence is higher than 60%, 
assuming that true adherence will be 80% or greater (one-sided 
exact binomial test with alpha 0.05). Phase 2: We will compute the proportion 
of patients with toxicity, along with a 95% exact confidence interval. Our 
institution’s historical toxicity rate among similar patients is about 80% and we 
aim to prove that the dietary intervention is non-inferior with an absolute 
margin of 10%, using an exact binomial test. With a total sample size of 90 
and assuming that true toxicity will be 80% or lower, we have 82% power 
(with one-sided alpha of 0.05). 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
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Schema 
 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
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 INTRODUCTION 
1
This document is a protocol for a human research study. This study is to be conducted 
according to US and international standards of Good Clinical Practice (FDA Title 21 part 
312 and International Conference on Harmonization guidelines), applicable government 
regulations and Institutional research policies and procedures.  
 Specific Aims and Hypothesis 
1.1
We hypothesize that a dietary change such as fasting may alter tumor biology. Further 
we hypothesize that a 25% reduction in caloric intake is a feasible intervention for 
early stage breast cancer patients to adhere to during radiation therapy. 
To this end, in this feasibility trial we will (1) investigate the feasibility of a clinical trial 
administering ionizing radiation with concurrent CR for the treatment of breast cancer 
(2) Acute skin toxicity as defined by the National Cancer Institute Common Toxicity 
Criteria (NCI CTCv.4 for skin reaction, pain and the occurrence of moist 
desquamation) will be followed to ensure noninferiority as compared with historical 
controls. (3) investigate measurable changes of patient characteristics along with 
serum markers from CR to determine a metric for evaluating this treatment in future 
studies.  
The use of caloric restriction as a novel intervention has the potential to change the 
biology of tumors and enhance the clinical benefit of standard cancer therapies. If this 
trial is successful and it is determined that patients can achieve successful caloric 
restriction during breast cancer treatment, the long term goal will be to open a larger 
study to determine if this treatment is more efficacious than using radiation alone. 
 Background and Rationale 
1.2
CR, or a diet modification aiming to reduce the total intake of calories by 20-30%, has 
been shown to increase longevity across multiple species.  Recently, there has been 
growing interest in the potential role of CR as a treatment modality for age-related 
diseases such as cancer because an increasing body of literature has demonstrated 
that there is a metabolic component to both carcinogenesis and tumor progression. In 
fact, many of the molecular pathways that are induced by CR, such as IGF1-R, Akt 
and mTOR pathways, are also known to be perturbed in cancer and are currently 
targets of novel cancer therapies. Therefore, alteration of multiple steps in these 
pathways by CR may render cancer cells more susceptible to standard cytotoxic 
treatment with radiation therapy. 
CR has been shown to decrease the incidence and progression of spontaneous 
breast cancers in murine models, and to protect normal tissue during chemotherapy.  
Our preliminary results show that CR represses tumor growth in an additive manner 
when combined with radiation in 2 different aggressive murine models (4T1 and 
67NR) of breast cancer (Fig 1).  Our results at the molecular level demonstrate that 
various components of the IGF-1R pathway are downregulated with CR and RT used 
separately, and are further decreased by the combination of treatments, suggesting a 
role for CR in the observed repression of tumor growth (Fig 2).   

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
10 
Figure 1: Tumor re-growth-delay curves for tumors created from 4T1 breast cancer cell 
line: Ten mice were treated with either: ad libitum (AL) diet, radiation (RT), a 30% reduction in 
their calories (CR), or CR + RT. Compared to the AL cohort, for 4T1 tumors at 1000mm3 RT 
produced a 23% growth delay, CR 56%, and CR+RT 82%.  
 
 
Figure 2. Expression of members of the IGF-1R pathway. RT-PCR was performed for 
molecules in the IGF-1R pathway(IGF-1R, IRS, PIk3ca, and mTOR).  For all of these 
molecules, CR, radiation, and the combination of both treatments resulted in downregulation 
which implicates this pathway in mediating the tumor regression noted.   
 
Although the preclinical data appears promising, it is unknown if patients will want to 
or be able to adhere to a reduction in calories during radiation therapy.  In the 
radiation clinic, many patients inquire about potentially beneficial dietary alterations. 
Although CR requires a significant commitment, we have shown through a TJUH IRB 
approved questionnaire that 75% of breast cancer patients queried at our institution 
would be interested in enrolling on such a diet related intervention trial (manuscript 
under review).  Because CR may act as a complementary therapeutic modality in the 
treatment of women with breast cancer, its full capacity as a therapeutic intervention 
needs to be assessed.   
It seems logical to propose that combining CR with genotoxic therapies such as 
radiation, in the treatment of breast cancer, could both retard tumor progression as 
well as confer significant therapeutic advantage by increasing the response of tumors 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
11 
to the cytotoxicity of standard therapies.  Therefore, in this proposal, we intend to 
investigate the feasibility of administering CR in combination with radiation therapy for 
early stage breast cancer, employing a clinical trial and evaluating biomarkers to 
monitor the progress of the trial.  In addition, we lay the groundwork for identifying 
tools that will assist patients with compliance, and we determine which may be most 
beneficial for women to use in a larger randomized trial based on the results obtained 
here.  
Specific Aim 1: In a clinical trial, will investigate the ability of CR to modulate 
the effects of radiation in the treatment of early breast cancer. Aim 1a. Adherence 
will be assessed and is defined for each patient as achieving 25% reduction of her 
normal caloric intake (weekly average of diet journals), during at least 80% of the days 
during the intervention. Aim 1b. Acute skin toxicity as defined by the National Cancer 
Institute Common Toxicity Criteria (NCI CTCv.4 for skin reaction, pain and the 
occurrence of moist desquamation) will be followed to ensure noninferiority as 
compared with historical controls. Specific Aim 2: Investigate measurable changes 
of patient characteristics along with serum markers from CR to determine a 
metric for evaluating this treatment in future studies. Patient characteristics such 
as weight, vital signs, body fat measurements, psychosocial evaluation and outcomes 
will be monitored. Additionally, members of the IGF-1R-AKT pathway, and glucose 
and insulin in the serum, will be assessed to create a molecular signature of response 
to this therapy.   
The innovative use of caloric restriction as a novel therapeutic option has the potential 
to change the biology of tumors and enhance the clinical benefit of current treatments 
for breast cancer. If patients are noted to be compliant, we will be able to open a 
larger study to determine if the combination of radiation and caloric restriction is more 
efficacious than radiation alone. 
 Study Therapy 
1.3
Baseline caloric intake will be assessed by food diaries for 7-10 days prior to radiation 
treatment planning. Recommendations by nutritional counseling will be made to 
decrease total caloric intake by 25% and the patient will begin this diet immediately 
after the planning session and for 2 weeks before starting radiation. The patient will 
then remain on this calorically restricted diet as measured by food diaries until 
completion of radiation treatment and for an additional 2 weeks for a total of 10 weeks. 
Restriction of calories is the primary objective of dietary modification and will be 
tailored to each patient by the discretion of the recommending physician in Integrative 
Medicine to ensure overall nutrition. Diet guidelines and compliance will be reviewed 
at weekly on-treatment visits by study staff including physicians and diet counselors. 
 Preclinical Data 
1.4
Delaying Tumor Regrowth using Caloric Restriction and Radiation 
An early focus of our laboratory was the use of CR to reduce tumor proliferation and 
progression in breast cancer. We first generated a reproducible mouse model to 
assess various modalities of treatment. Specifically, we tested the syngeneic and 

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12G.616 Protocol v4.2 (04Jan2016) 
13 
Figure 4: Tumor re-growth-delay curves for tumors created from 4T1 breast 
cancer cell line. Ten mice were treated with either: ad libitum (AL) diet, radiation 
(RT), a 30% reduction in their calories (CR), or CR + RT. Compared to the AL cohort, 
for 4T1 tumors at 1000mm3 RT produced a 23% growth delay, CR 56%, and CR+RT 
82%.  
 
CR alters the IGF-1R survival-signaling pathway 
To determine if altering the IGF-1R pro-survival pathway might be responsible for the 
additive tumor regression noted between CR and irradiation, qRT-PCR was performed 
on grossly dissected 4T1 tumors from the previous experiment using primers for IGF-
1R, IRS, PIk3ca, and mTOR. 
Figure 5: Expression of members of the IGF-1R pathway.  RT-PCR was performed 
for molecules in the IGF-1R pathway(IGF-1R, IRS, PIk3ca, and mTOR).  For all of 
these molecules, CR, radiation, and the combination of both treatments resulted in 
downregulation which implicates this pathway in mediating the tumor regression 
noted.   
 
These results (Fig. 5) demonstrated that multiple molecules in the IGF-1R/AKT 
pathway are downregulated with CR alone or in combination with radiation.  Since the 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
14 
IGF-1R/AKT is involved in apoptosis and based on these results we propose that this 
work warrants further investigation of this pathway is warranted in order to determine 
whether pathway components contribute to the beneficial effects of CR in breast 
cancer. 
 Clinical Data to Date 
1.5
Although there have been no published trials assessing radiation therapy with a diet 
modification to date, there are now a number of registered trials 
(www.clinicaltrials.gov) assessing a ketogenic diet with cancer therapy for lung 
cancer, pancreatic cancer, primary brain tumors and metastatic cancer. 
There are published trials in the non-oncologic realm however; showing that caloric 
restriction is feasible and patients are able to be compliant in other diseases or in 
healthy volunteers. For example, the Comprehensive Assessment of Long-term 
Effects of Reducing Intake of Energy (CALERIE) is a multi-center randomized 
controlled trial that placed patients on a 25% caloric reduction for 2 years.  A number 
of early assessments from this trial have now been published, revealing that this 
regimen is feasible and that the fasting insulin level was decreased with diet 
modification.  Cognitive function was not significantly altered in individuals undergoing 
CR.  Other data exists from the Biosphere 2 project in Arizona, where patients were 
kept on a CR diet of1,780 kcal/day for 2 years.  This regimen would be more similar to 
those likely used in human cancer CR clinical trials.  One-year CR studies have 
shown feasibility and adherence metrics have been developed as well.   
Determining Interest in a CR Clinical Trial: Many patients express an interest in dietary 
changes they can make to improve their cancer survival but the data supporting such 
interventions is scarce.  To begin to develop a protocol for using CR to treat patients, 
we set out to assess the feasibility of using CR in a clinical setting. Specifically, we 
distributed an IRB-approved questionnaire to our oncology patients querying patient 
interest in participating in a CR study. We found that 75% would participate in a CR 
trial. The patients identified several tools they believed would help them with dietary 
trial adherence including speaking with a dietician weekly and weekly phone 
conversations with the physician.  This demonstrates that there is patient interest in 
dietary interventions and that a trial using CR could successfully accrue patients. We 
have since worked with the Integrative Medicine Department to develop a strategy to 
implement a CR diet and to monitor and ensure adherence.  
 Dose Rationale and Risk/Benefits 
1.6
The patients will undergo a 25% reduction in total caloric intake since this is a) the 
reduction used in other clinical trials that employ caloric restriction and, b) the 
definition of caloric restriction and the percent reduction noted to effect molecular 
targets in the IGF pathway. 
The patients will undergo CR for a total of 10 weeks because previous studies have 
noted that the maximum effect of CR seems to be reached at 5 weeks. It is then 
important to incorporate at least 5 weeks for stabilization of physiologic processes 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
15 
under caloric restriction [1].  
The diet modification proposed should not induce many risks, and every effort will be 
made to insure that patients are receiving adequate overall nutrition.  Although some 
patients may experience weight loss and fatigue, other risks should be minimal. These 
risks may include: decreased bone mineral density, decreased muscle mass and 
strength, depression, decreased sex drive, fatigue, irritability, fainting, rashes, 
acidosis, malnutrition, constipation, dehydration, cholelithiasis and reversible 
amenorrhea.  
Because obesity has been proven a poor prognostic factor in those patients with 
breast cancer, dietary intervention may be ideal for improving outcomes for these 
patients who decrease their caloric intake. 
 STUDY OBJECTIVES 
2
 Primary Objective 
2.1
Aim 1a. Investigate the feasibility of a clinical trial administering ionizing radiation with 
concurrent CR for the treatment of breast cancer. True adherence will be defined as a 
successful reduction of 25% of total calories based on diet journals in at least 80% of 
the logged events. 
Aim 1b. Acute skin toxicity as defined by the National Cancer Institute Common 
Toxicity Criteria (NCI CTCv.4 for skin reaction, pain and the occurrence of moist 
desquamation) will be followed to ensure noninferiority as compared with historical 
controls. 
 Secondary Objective 
2.2
Investigate measurable changes of patient characteristics and tissue and serum from 
fasting/CR conditions to determine a metric for evaluating this treatment in future 
studies. 
 
Weight: Weight will be monitored by body mass index, at baseline, week 1, 3, 5 and 7, 
conclusion and 4 weeks after diet is complete. Body fat measurements via calipers and 
bioimpedance which will be done at baseline, conclusion and 4 weeks after diet is 
completed. Vital signs will be monitored weekly. 
 
Serum: 
 
At initiation of diet, conclusion of diet and 4 weeks after diet is complete, fasting 
labs will be drawn: 
 
Clinical Lab: CBC, basic metabolic panel, hemoglobin A1C, triglycerides, 
insulin, IGF-1, erythrocyte sedimentation rate (ESR), adiponectin, leptin 
and estradiol 
 
Other Serum Markers:  IGF-1R, IRS-1, genomic and or proteomic 
analysis 
 
At week 5: a fasting insulin level will be evaluated. 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
16 
 
Psycho-social evaluation:  Patients will have psycho-social evaluation using the FACT-
B test and the PROMIS cancer fatigue short form at baseline, week 5, conclusion and 4 
weeks after conclusion. 
 
Outcomes: Local recurrence, progression free survival, distant metastases and overall 
survival will be assessed through patient records after study has been completed. 
 
Toxicity: acute skin reaction or pain using the National Cancer Institute Common Toxicity 
Criteria (NCI CTC) version 4.0 scale22 will be assessed. Number of patients 
experiencing toxicity and time to occurrence of toxicity will be recorded. This toxicity will 
be compared to historical controls from TJUH who have also been treated for a 6 week 
course of radiation.  
 Study Design 
3
 General Design 
3.1
 
This is a pilot trial to assess feasibility and toxicity of the dietary intervention during radiation. 
 
Expected duration of subject participation: approximately 20 weeks, with 10 weeks of diet and 
follow up 
 
Section 6.1 outlines the specific trial periods. 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
17 
 
 Primary Study Endpoints 
3.2
Objective: Investigate the feasibility of a clinical trial administering ionizing radiation 
with concurrent CR for the treatment of breast cancer. True adherence will be defined 
as a successful reduction of 25% of total calories based on diet journals in at least 
80% of the logged events. Acute skin toxicity as defined by the National Cancer 
Institute Common Toxicity Criteria (NCI CTCv.4 for skin reaction, pain and the 
occurrence of moist desquamation) will be followed to ensure noninferiority as 
compared with historical controls. 
To obtain baseline caloric intake, patients will keep food diaries for 7 to 10 days. On 
the basis of these diaries, a caloric intake will be computed for each day. Each 
patient's baseline (pre-diet) caloric intake will then be the average caloric intake in this 
pre-diet phase. The target caloric intake during the diet phase will be set to 75% of 
this baseline average (25% restriction). 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
18 
The diet phase will be defined as the entire length that a patient is on the calorically 
restricted diet. This includes a minimum of 2 weeks before the patient starts radiation 
therapy and a minimum of 2 weeks after completion of radiation therapy. This will 
guarantee that patients have been on the diet for a minimum of 10 weeks, regardless 
of whether or not the patients have exceeded the 10 weeks. In the diet phase, patients 
will also keep daily food diaries. An average daily caloric intake will be computed 
for each week. If that daily average is more than the restricted target or if there are 
fewer than 4 diaries during any given week, that week will be considered as non-
adherent. Overall adherence with the diet intervention over the entire study will be 
defined as at least 80% of all logged events meeting the diet restriction target. 
 Secondary Study Endpoints 
3.3
Investigate measurable changes of patient characteristics and tissue and serum from 
fasting/CR conditions to determine a metric for evaluating this treatment in future 
studies. 
 
Weight: Weight will be monitored as a percent change and by body mass index as 
weight in kg divided by height in meters squared, at baseline, week 1, 3, 5 and 7, 
conclusion and 4 weeks after diet is complete.  
 
Body Fat Measurement: Body fat percentage will be done at baseline, conclusion and 4 
weeks after diet is complete and will be determined by the Durnin-Womersley 4-fold 
technique. All skinfold measurements should be made on the right side of the body in 
mm using a body fat caliper. Body fat caliper will be placed 1 cm away from thumb and 
finger, perpendicular to the skinfold, and halfway between the crest and base of fold. A 
pinch will be maintained with the body fat caliper for 1 to 2 seconds before reading the 
caliper. Duplicate measurements will be taken at each site, allowing time for skin to 
regain normal texture and thickness. Measurements will be taken at the: 
 
Biceps: Measured on a vertical fold at the upper arms frontside, half way between 
shoulder and elbow. 
 
Triceps: Measured on a vertical fold at mid of the upper arms backside. 
 
Scapula: Measured on a diagonal fold on the back, at the lower edge of the scapula. 
Angle of inclination should be 45°, clockwise. 
 
Hip: Measured on a diagonal fold straight over the pelvis, close to the navel. Angle of 
inclination should be 30°, clockwise. 
 
Bioimpedance: Bioimpedance will be taken at baseline, conclusion and 4 weeks after 
diet is completed and will be measured in Ω/m2. 
 
Vitals: Vital signs including temperature, blood pressure, heart rate and respiratory rate 
will be monitored weekly. 
 
Serum (collection procedures detailed in Appendix VI): 
 
At initiation of diet, conclusion of diet and 4 weeks after diet is complete, fasting labs 
will be drawn: 
 
Clinical Lab: CBC, basic metabolic panel, hemoglobin A1C, triglycerides, insulin, 
IGF-1, erythrocyte sedimentation rate (ESR), adiponectin, leptin and estradiol 
 
Other Serum Markers:  IGF-1R, IRS-1, genomic and/or proteomic analysis 
 
At week 5: a fasting insulin level will be evaluated. 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
19 
 
Psycho-social evaluation:  Patients will have psycho-social evaluation using the FACT-
B test and the PROMIS cancer fatigue short form at baseline, week 5, conclusion and 4 
weeks after conclusion. (Forms detailed in CRFs in Appendix VII) 
 
Outcomes: Local recurrence, progression free survival, distant metastases and overall 
survival will be assessed through patient records after study has been completed. 
 
Toxicity: acute skin reaction or pain using the National Cancer Institute Common Toxicity 
Criteria (NCI CTC) version 4.0 scale22 will be assessed. Number of patients 
experiencing toxicity and time to occurrence of toxicity will be recorded (see Appendix III 
for toxicity scale). This toxicity will be compared to historical controls from TJUH who 
have also been treated for a 6-6.5 week course of radiation.  
 Primary Safety Endpoints 
3.4
Acute toxicities will be evaluated by the CTCAE, Version 4.0. (http://ctep.info.nih.gov). 
If a patient has a serious adverse event such as all unexpected hospitalizations and 
all grade 4 and 5 SAEs, the patient will be removed from the trial. See Appendix III for 
scale. 
 Subject Selection and Withdrawal 
4
Patients must have baseline evaluations performed prior to the first dose of study drug 
and must meet all inclusion and exclusion criteria. Results of all baseline evaluations 
will be reviewed by the Principal Investigator prior to enrollment, to verify that all 
inclusion and exclusion criteria have been satisfied. In addition, the patient must be 
thoroughly informed about all aspects of the study, including the study visit schedule 
and required evaluations and all regulatory requirements for informed consent. The 
written informed consent must be obtained from the patient prior to screening 
procedures being performed. The following criteria apply to all patients enrolled onto the 
study unless otherwise specified. 
 Inclusion Criteria 
4.1
 
Pathologically proven diagnosis of DCIS or invasive breast cancer  
1.
 
Ability to have breast conservation as determined by the judgment of the radiation 
2.
oncologist, for which the radiation oncologist has determined that he or she will only 
treat the whole breast and not regional lymph nodes 
 
The patient must be female 
3.
 
Age ≥ 18 
4.
 
If multifocal breast cancer, then it must be able to be resected through a single 
5.
lumpectomy incision  
 
Appropriate stage for protocol entry, including no clinical evidence for distant 
6.
metastases, based upon the following minimum diagnostic workup: 
 
History/physical examination, including breast exam and documentation of 
weight and Karnofsky Performance Status of 80-100% at study entry.  
 
Women of childbearing potential must be non-pregnant and non-lactating and willing to 
7.
use medically acceptable form of contraception during radiation therapy 
 
Patient must capable of and provide study specific informed consent prior to study 
8.
entry 
 
BMI ≥21  
9.

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
20 
 Weight ≥100lbs   
10.
 No prior history of non-breast invasive malignancies in the past 1 years  
11.
 Patient must not have any of the following severe, active co-morbidity, defined as 
12.
follows: 
 
Unstable angina and/or congestive heart failure requiring hospitalization within 
the last 6 months 
 
Transmural myocardial infarction within the last 6 months 
 
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of 
registration; 
 
Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness 
requiring hospitalization or precluding study therapy within 30 days before 
registration; 
 
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; 
note, however, that laboratory tests for liver function and coagulation parameters 
are not required for entry into this protocol 
 
Acquired Immune Deficiency Syndrome (AIDS) or HIV positive based upon 
current CDC definition; note, however, that HIV testing is not required for entry 
into this protocol. The need to exclude patients with AIDS or HIV from this 
protocol is necessary because anti-retrivirals may alter patient metabolism. 
 
Gastrointestinal/Malabsorption disorder at the discretion of the Principal 
Investigator 
 
Inflammatory Bowel Disease 
 
Celiac Disease 
 
Chronic Pancreatitis 
 
Chronic Diarrhea or Vomiting 
 
Active Eating Disorder 
 
 
 Patient must not have active systemic lupus erythematosus, or any history of active 
13.
scleroderma, or dermatomyositis with active rash 
 No prior radiotherapy to the ipsilateral breast or prior radiation to the region of the 
14.
breast that would result in overlap of radiation therapy fields 
 Not currently taking steroids 
15.
 No history of or current active drug/alcohol dependence.   
16.
 No patients being decisionally impaired. 
17.
 Exclusion Criteria 
4.2
 
Patient is not a candidate for breast conservation. 
1.
 
Patient is male. 
2.
 
Age <18 years 
3.
 
Patient requires regional lymph node irradiation therapy 
4.
 
Patient has evidence of distant metastases 
5.
 
Karnofsky Performance Status less than 80% within 60 days prior to study. 
6.
 
Ipsilateral mammogram done greater than 6 months prior to study. 
7.
 
Women of childbearing potential with a positive serum beta hCG. 
8.
 
Patient unable to consent or comply with study guidelines. 
9.
 BMI < 21 
10.
 Weight < 100lbs 
11.
 Unintentional weight loss ≥10% in the last 3 mos 
12.

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
21 
 Prior invasive non-breast malignancy unless disease free for a minimum of 1 year prior 
13.
to registration 
 Two or more breast cancers not resectable through a single lumpectomy incision 
14.
 Non-epithelial breast malignancies such as sarcoma or lymphoma 
15.
 Prior radiotherapy to the ipsilateral breast or prior radiation to the region of the breast 
16.
that would result in overlap of radiation therapy fields 
 Severe, active co-morbidity, defined as follows: 
17.
 
Unstable angina and/or congestive heart failure requiring hospitalization within 
the last 6 months 
 
Transmural myocardial infarction within the last 6 months 
 
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of 
registration; 
 
Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness 
requiring hospitalization or precluding study therapy within 30 days before 
registration; 
 
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; 
note, however,that laboratory tests for liver function and coagulation parameters 
are not required for entry into this protocol 
 
Acquired Immune Deficiency Syndrome (AIDS) or HIV positive based upon 
current CDC definition; note,however, that HIV testing is not required for entry 
into this protocol. The need to exclude patients with AIDS or HIV from this 
protocol is necessary because anti-retrivirals may alter patient metabolism. 
 Active systemic lupus erythematosus, or any history of active scleroderma, 
18.
dermatomyositis with active rash 
 Active Gastrointestinal/Malabsorption disorder at the discretion of the Principal 
19.
Investigator 
 
Inflammatory Bowel Disease 
 
Celiac Disease 
 
Chronic Pancreatitis 
 
Chronic Diarrhea or Vomiting 
 
Active Eating Disorder 
 Current use of steroids 
20.
 Active drug/alcohol dependence or abuse history.   
21.
 Decisionally impaired patients. 
22.
 Gender/Minority/Pediatric Inclusion for Research 
4.3
This protocol will enroll all women with breast cancer and will include minorities in the 
research protocol. Pediatric patients are excluded. 
 Subject Recruitment and Screening 
4.4
Patients who are 18 year of age or older and are candidates for breast conservation 
for their breast cancer are eligible for the study. Patients can be recruited from the PI, 
co-investigators’ or referring physician’s clinical practices. We have designed a 
brochure to try and help with patient recruitment. This brochure is attached in the 
Appendix VIII Section. Potential study subject should be referred to PI or study 
designated research nurse/research associate. Appropriate laboratory or diagnostic 
testing necessary to meet any noted inclusion or exclusion criteria will be ordered 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
22 
through the recruiting physician. PI of the study or study designated research 
nurse/research associate will screen and determine the final eligibility of the subject 
for enrollment.  
 Early Withdrawal of Subjects 
4.5
 When and How to Withdraw Subjects 
4.5.1
Patients will be informed that they have the right to withdraw from the study at any 
time for any reason, without prejudice to their medical care. The investigator also 
has the right to withdraw patients from the study for any of the following reasons: 
1. Intercurrent illness 
2. Occurrence of an unacceptable adverse event such as a Grade ≥ 4 toxicity or ≥ 20% 
weight 
3. Missing more than 3 consecutive days of planned radiation 
4. Patient request 
5. Protocol violations based on the judgment of PI 
6. Non-compliance 
7. Administrative reasons 
8. Failure to return for follow-up 
9. General or specific changes in the patient’s condition unacceptable for further 
treatment in the judgment of the investigator 
10. Patients may withdraw from the study voluntarily at any time; however, the Principal 
Investigator reserves the right to remove patients from the study for any of the 
following reasons. 
11. Radiation toxicity becomes too severe and the patient can no longer tolerate 
consecutive radiation treatments as determined by treating radiation oncologist. 
12. Patients are hospitalized for another condition that is unrelated to breast cancer. 
Particularly admissions lasting longer than 4 days. 
13. Patients develop any of the exclusionary conditions during treatments including: 
hepatic insufficiency, diabetes, disorders requiring corticosteroid treatment, renal 
failure or pregnancy. 
14. Patients become sexually active and do not wish to use contraception or patients 
discontinue previous method of contraception and remain sexually active. 
At the time of withdrawal, all study procedures outlined for the End of Study visit 
should be completed. The primary reason for a patient’s withdrawal from the study 
is to be recorded in the source documents. 
 Data Collection and Follow-up for Withdrawn Subjects 
4.5.2
According to FDA regulations, when a subject withdraws from the study, the data 
collected on the subject to the point of withdrawal remains part of the study 
database and may not be removed. 
A subject who is withdrawing needs to state whether he/she wishes to provide 
continued follow-up and further data collection subsequent to withdrawal from the 
interventional portion of the study.  

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
23 
If a subject withdraws from the interventional portion of the study, but agrees to 
continued follow-up of associated clinical outcome information as described in the 
previous bullet, the subject will continue follow up visit and evaluation per the 
protocol. 
If a subject withdraws from the interventional portion of a study and does not 
consent to continued follow-up of associated clinical outcome information, study 
data related to the subject collected prior to the subject’s withdrawal from the study 
will included in the study analysis. However, the subject’s clinical data will not be 
used for dose escalation determination. 
 Study Drug/Therapy  
5
 Description 
5.1
Baseline caloric intake will be assessed by food diaries for 7 to 10 days prior to 
radiation treatment planning. Recommendations by nutritional counseling will be made 
to decrease total caloric intake by 25% and the patient will begin this diet immediately 
after the planning session and for a minimum of 2 weeks before starting radiation. The 
patient will then remain on this calorically restricted diet as measured by food diaries 
until completion of radiation treatment and for a minimum of 2 weeks after the 
completion of the radiation course. This is done to ensure that he patients undergo 
caloric restriction for a minimum of 10 weeks +/-1-2 weeks. 
Restriction of calories is the primary objective of dietary modification and will be 
tailored to each patient by the discretion of the recommending physician in Integrative 
Medicine to ensure overall nutrition. Diet guidelines and compliance will be reviewed 
at weekly on-treatment visits by study staff including physicians and diet counselors. 
 Treatment Regimen 
5.2
 Prior to Radiation: 
5.2.1
Caloric restriction to 75% of normal calorie intake will begin when patients present 
for radiation treatment planning. Prior to this, patients will have recorded their daily 
intake in food journals for 2 weeks. Patients will remain on this calorically restricted 
diet until completion of radiation treatment for a total of 10 weeks.  
Restriction of calories is the primary objective of dietary modification; however, to 
patients will be encouraged to maintain adequate nutrient intake. Diet guidelines 
and adherence will be enforced at weekly on-treatment visits by study staff 
including physicians and diet counselors. 
 Risks of Caloric Restriction 
5.3
Likely (>10%) 
 
Weight loss 
 
Fatigue 
 
Irritability 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
24 
Possible 
 
Decreased bone mineral density 
 
Decreased muscle mass and strength 
 
Dehydration 
 
Constipation 
 
Depression 
 
Fainting 
Rare (<2%) 
 
Cholelithiasis 
 
Reversible amenorrhea 
 
Malnutrition 
 
Reduced sex drive 
 
Acidosis 
 Method for Assigning Subjects to Treatment Groups 
5.4
As a feasibility trial, all patients will be expected to be on treatment as defined by 
caloric restriction, radiation therapy and nutritional counseling.  
 Preparation and Administration of Study Drug/Therapy 
5.5
Patients will be expected to keep food diaries for 7 to 10 days prior to radiation 
treatment planning in order to calculate each patients appropriate calorie intake during 
the treatment period. Initially, patients will have a consultation with integrative 
medicine and they will meet weekly with research staff for nutritional guidance and 
behavioral counseling to maintain their dietary modification. Patients will be expected 
to record their dietary intake on a daily basis while on treatment and these food 
journals will be collected weekly and modifications will be suggested accordingly. 
Patients will ultimately be responsible for modifying their diet as recommended to 
them.  
 Compliance Monitoring 
5.6
Adherence to dietary modification will be monitored by self-reported calorie intake in 
food journals that will be collected on a weekly basis. Patients will be expected to 
complete food diaries accurately to represent the type and quantity of food they 
consumed. Patients who have internet access at home and are comfortable with 
computers will be given the option of using an online food diary that is password 
protected, but viewable by the study staff.  Should patients select this option, they will 
be assigned a username and create their own password.  
The mean weekly caloric intake will be measured and adherence will compared with 
their baseline evaluation. Patients will have to maintain a weekly 25% reduction of 
caloric intake for 80% of the logged events in order to be considered compliant for this 
trial. 
See Appendix IX for printed food diary and access to online food diary. 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
25 
 Prior and Concomitant Therapy 
5.7
Patients should continue taking their daily medications on a regular basis. Patients 
should not be taking corticosteroids, anti-retrovirals that would exclude them from 
participation.  
 Study Procedures 
6
 Treatment Overview  
6.1
 
 
Wk 1 
Wk 2 
Wk 3-4 
Wk 5-10.5 
Wk 11-12 
Patients post-
lumpectomy  
Day 
All 
All 
All 
1    2    3    4    5    6    7  
All 
Diet 
Normal 
Normal 
CR Diet 
Continue CR Diet 
CR Diet 
Radiation 
None 
Simulation 
None 
 
None 
 Study Visit Schedule 
6.2
 Screening 
6.2.1
Eligibility of patients will be verified based on clinical staging and any need for 
adjuvant chemotherapy as well as previously stated eligibility criteria. Those 
eligible patients will receive detailed information about the study including a step-
by-step outline of proposed treatment including radiation therapy and diet 
modification. Patients will be informed of possible risks and benefits. Informed 
consent will be obtained from patients. A full history and physical examination will 
be performed on consented patients. Baseline weight and BMI will be taken. In 
addition, blood will be drawn for eligibility measurements of beta-hCG if 
appropriate.  
 Phase I—Pre-treatment 
6.2.2
Visit 1: Patients will report to the Radiation Oncology Department for radiation 
treatment planning to include CT simulation. Food diaries from the previous 7-10 
days will be collected and analyzed to create a diet plan for each patient. 
Integrative medicine will meet with patients to counsel them on lifestyle changes 
and behavioral aspects of dietary modification. Dietary counselors will give patients 
guidelines for dietary modification including the appropriate amount of calories that 
each patient should be receiving and what kinds of foods they should avoid or eat 
more of. Nutritional counseling will be done using behavioral cues to encourage 
adherence (see Appendix V for worksheets). Patients will be instructed to begin 
their new diet starting at this visit and to continue logging foods into their journals. 
They will complete the journal daily. Patients will undergo a focused examination to 
assess initial breast appearance and texture for comparison as patients receive 
radiation therapy. Fasting blood will be drawn for baseline laboratories at this visit. 
Clinical measurements will include CBC w/diff, CMP, HbA1c, IGF-1, adiponectin, 
leptin, estradiol, triglycerides, insulin, ESR. Separately, blood samples will also be 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
26 
analyzed for the following: IGF-1R, IRS-1 and other experimental endpoints such as 
genomic or proteomic alterations. Baseline psychosocial evaluation will be done 
using the FACT-B form as well as a baseline fatigue assessment using the 
PROMIS cancer fatigue short form (see appendix XI). Weight, height, vital signs, 
bioimpedance and caliper measurements will be done. 
Phone Intervention: Patients will be contacted at least once a week during the 
time they are keeping the food journal to determine if help is needed. 
Visit 2: Week 1 or day 7 (±2 day) of diet. Weight will be measured and vital signs 
will be taken. Food diary from previous week to be collected, as well as 24hr recall 
of diet. 
Visit 3: Week 2 of diet. Weight will be measured and vital signs will be taken. Food 
diary from previous week to be collected, as well as 24hr recall of diet. 
 Phase II—Visits During Radiation Treatment 
6.2.3
Visit 4-9: Patients will be monitored for acute radiation toxicity including skin 
changes and desquamation. Patients will be questioned and examined to ensure 
general health and will be reassured about radiation-related side effects. Patients 
will turn in their food diary from the previous week and dietary counselors will 
review these with the patients to determine how they can continue to comply with 
dietary modification. At each visit, a 24hr recall of diet will be asked of the patient 
and compared with the diet journal to determine the self reporting accuracy. Each 
week during this period, patients will be counseled on their diet and given 
behavioral modification lessons corresponding to specific weeks in the diet (see 
Appendix V for worksheets). Weight will be taken at weeks 3, 5 and 7 of the diet, 
corresponding to weeks 1, 3 and 5 of radiation and vital signs will be performed 
weekly. FACT-B psychosocial assessment will be given at visit 7along with the 
PROMIS cancer fatigue short form. In addition, at visit 7 (week 5 of diet) patients 
will have a fasting blood draw done for insulin level.  
Radiation will be planned to be administered 5 days a week, Monday through 
Friday. Radiation is given for approximately 6-6.5 weeks or 30-33 treatments. 
 Phase III—Post Radiation Treatment 
6.2.4
Visit 10: Week 9 of diet,for scheduling purposes. Weight and vital signs will be 
measured. Patients will be monitored for acute radiation toxicity including skin 
changes and desquamation. Patients will turn in their food diary from the previous 
week and dietary counselors will review these with the patients to determine how 
they can continue to comply with dietary modification. A 24hr recall of diet will be 
asked of the patient and compared with the diet journal to determine the self-
reporting accuracy. Patients will be counseled on behavioral modification for the 
final week of their diet (see Appendix V for worksheet). Weight and vital signs will 
be measured. 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
27 
Visit 11: Week 10 of diet, +/- 3-5 days for scheduling purposes, last day of diet; 
Fasting blood draw to be done for CBC, basic metabolic panel, hemoglobin A1C, 
triglycerides, insulin, IGF-1, erythrocyte sedimentation rate (ESR), adiponectin, 
leptin and estradiol. Separately, blood will be analyzed for IRS-1, IGF-1R. Weight 
and vital signs will be measured. Conclusion bioimpedance and caliper 
measurements will be taken. Patients will be monitored for acute radiation toxicity 
including skin changes and desquamation. Patients will turn in their food diary from 
the previous week and dietary counselors will review these with the patients to 
determine how they can continue to comply with dietary modification. A 24hr recall 
of diet will be asked of the patient and compared with the diet journal to determine 
self-reporting accuracy. Patients will complete the FACT-B psychosocial evaluation 
as well as the PROMIS cancer fatigue short form.  
Visit 12: 4 weeks after completion of diet. Fasting blood draw to be done for CBC, 
basic metabolic panel, hemoglobin A1C, triglycerides, insulin, IGF-1, erythrocyte 
sedimentation rate (ESR), adiponectin, leptin and estradiol. Separately, blood will 
be analyzed for IRS-1, IGF-1R. Weight, bioimpedence, caliper measurements and 
vital signs will be measured. Patients will be monitored for acute radiation toxicity 
including skin changes and desquamation. Patients will turn in their food diary from 
the last diet week. FACT-B and PROMIS cancer fatigue short form will be 
administered. 
 Study Flowchart 
6.3
Examination 
Pre-Treatment 
Radiation Treatment 
Post RT 
Follow-up 
 
Screening 
Surgery 
Sim 
Week of Caloric Restriction Diet  
 
 
 
 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
Visit Number 
0 
1 
2 
3 
D7 
4 
D14 
5 
6 
7 
8 
9 
1
0 
11 
12 
Las
t 
13 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Background Info 
(demographics, 
meds, medical 
history) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclus
ion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
H&P; 
Performance 
Status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Focused 
Physical 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
X 
Weight, BMI 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
Caliper 
Measurements, 
Bioimpedance 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
28 
Clinical Labs: 
CBC w/diff, 
CMP, HbA1c 
Serum: IGF-1, 
adiponectin, 
leptin, estradiol, 
triglycerides,  
fasting insulin, 
ESR 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
Fasting insulin 
level 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other Labs: 
IGF-1R, IRS-1,  
 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
FACT-B 
Psychosocial 
Evaluation 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
 
PROMIS cancer 
fatigue short 
form 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
Specimen sent 
to Pathology for 
histologic exam 
andER, PR, 
HER2 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Dietary 
Counseling  
X 
 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
Behavioral 
Counseling 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Food Diary 
Collected 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Acute Toxicity 
Assessment 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Key: 
H&P=Full history and physical exam 
 
Sim=Radiation simulation planning session 
 
RT=Radiation Therapy 
 
D7=Day 7 of caloric restriction diet; D14=Day 14 of caloric restriction diet 
 
Last=Final day of caloric restriction diet 
 Radiation Treatment 
6.4
 Dose Specifications 
6.4.1
 Breast: 50 Gy in 25 fractions of 2 Gy.  
6.4.1.1
 Lumpectomy PTV Cavity: Total dose will be 10-16 Gy in 5-8 fractions  
6.4.1.2
 Total radiation dose 60-66Gy 
6.4.1.3
 Technical Factors 
6.4.2
 The patient may be treated by photon or electron radiation therapy. Fields 
6.4.2.1
and treatment type will be up to the discretion of the treating radiation 
oncologist and may include but is not limited to 3D-RT, IMRT and en face.  

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
29 
 The guidelines for IMRT in this trial will conform to the policies set by the 
6.4.2.2
Advanced Technology Consortium (ATC) and the National Cancer Institute 
(NCI) http://atc.wustl.edu/home/NCI/NCI_IMRT_Guidelines.html 
 Megavoltage photon beams with energies ≥6 MV and megavoltage electron 
6.4.2.3
beams are required. 
 Localization, Simulation, and Immobilization 
6.4.3
 Simulation and treatment may be performed with the patient in the supine or 
6.4.3.1
prone position. 
 Patients should be optimally positioned with immobilization devices at the 
6.4.3.2
discretion of the treating physician such as alpha cradle casts, breast 
boards, wing boards. 
 Methods to minimize the cardiac exposure to RT like heart block, gating or 
6.4.3.3
breathhold are allowed at the discretion of the treating physician 
 For large-breasted patients, including those with a large inframammary skin 
6.4.3.4
fold, devices to improve positioning of the breast are permissible. 
 A treatment planning CT scan in the treatment position will be required to 
6.4.3.5
define the tumor bed for boost. 
 The CT required for generation of a virtual plan with 3DCRT or 
6.4.3.5.1
IMRT must be post-lumpectomy 
 Radio-opaque markers must be placed on external landmarks at the 
6.4.3.5.2
acquisition of the CT scan to facilitate contouring segmentation of 
the CT data-set. These markers should identify: 1) The lumpectomy 
incision 2) Additional markers to define the clinical borders of 
tangent fields (e.g. based on the palpable breast tissue and boney 
landmarks). 
 The CT should extend cephalad to start at or above the mandible 
6.4.3.5.3
and extend sufficiently caudally (or inferiorly) to the inframammary 
fold to encompass the entire lung volume. A CT scan image 
thickness of ≤0.5 cm should be employed. 
 External skin localizing marks, which may include permanent 
6.4.3.5.4
tattoos, are recommended for radiation daily localization and set-up 
accuracy. 
 Treatment Planning/Target Volumes 
6.4.4
 Planning isodose lines will be chosen by treating physician.  
6.4.4.1
 Target Volumes and Normal Structures 
6.4.4.2
 Lumpectomy CTV: Contour using all available clinical and radiographic 
6.4.4.3
information including the excision cavity volume, architectural distortion, 
lumpectomy scar, seroma and/or extent of surgical clips (clips are strongly 
recommended). Patients without a clearly identifiable lumpectomy bed do 
not need a boost. Lumpectomy CTV volume will be expanded by 1.5 to 2cm 
at the physicians discretion and the expanded volume (Lumpectomy PTV) 
will be treated. 
 Ipsilateral lung. This may be contoured with auto-segmentation with manual 
6.4.4.4

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
30 
verification. 
 Contralateral lung. This may be contoured with auto-segmentation with 
6.4.4.5
manual verification 
 Heart: The heart should be contoured beginning just inferior to the level in 
6.4.4.6
which the pulmonary trunk branches into the left and right pulmonary arteries 
(PA). Above the PA, none of the hearts 4 chambers are present. All the 
mediastinal tissue below this level should be contoured, including the great 
vessels (ascending and descending aorta, inferior vena cava). The heart 
should be contoured on every contiguous slice thereafter to its inferiormost 
extent near the diaphragm. If one can identify the esophagus, this structure 
should be excluded from the heart. One need not include pericardial fat, if 
present. Contouring along the pericardium itself, when visible, is appropriate. 
 Treatment Verification 
6.5
 Before first treatment:  
6.5.1
Portal films or images of each 3DCRT beam and an orthogonal pair for all patients 
must be obtained and approved by a physician prior to initiation of treatment. 
 Subsequent images or films:  
6.5.2
Subsequent treatment images may be obtained every fraction. At the minimum, 
orthogonal pair films or treatment images must be obtained prior to fraction number 
5 and every 5 fractions subsequently. The imaging modality and process should be 
performed based on the institutional guidelines. 
 Radiation Therapy Adverse Events 
6.6
All Radiation Therapy AEs will be scored according to the NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 4 
Short Term: Fatigue is an anticipated systemic reaction to radiation treatment. Skin 
erythema, desquamation, breast edema, breast tenderness and myositis are potential 
local reactions. 
Long Term: Long term effects possibly include radiation pneumonitis, rib fractures, 
second malignancy and for left-sided lesions cardiac complications 
 STATISTICAL PLAN 
7
 Sample Size Determination 
7.1
The study will enroll a total of 90 patients. For Phase 1, with a sample size of 40, 
the study has 83% power to establish that adherence is higher than 60%, assuming 
that true adherence will be 80% or greater (one-sided exact binomial test with alpha 
0.05). 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
31 
 Statistical Methods 
7.2
Primary endpoint (adherence). We will compute the proportion of patients who are 
adherent to the diet restriction (as defined in section 3.2), along with a 95% exact 
confidence interval. We will also use an exact binomial test (with a one-sided alpha of 
0.05) to test whether adherence is greater than 60%.  
Aim 1b. We will compute the proportion of patients with toxicity, along with a 95% 
exact confidence interval. Our institution’s historical toxicity rate among similar 
patients is about 80% and we aim to prove that the dietary intervention is non-inferior 
with an absolute margin of 10%, using an exact binomial test. With a total sample size 
of 90 and assuming that true toxicity will be 80% or lower, we have 82% power (with 
one-sided alpha of 0.05). 
Secondary endpoints. The change in body fat measurement between baseline and the 
end of the study will be analyzed via a paired t-test. Weight changes over time will be 
assessed by modeling BMI as a function of time (baseline, diet weeks 1, 3, 5, 7, and 
10) via mixed-effects regression.  The patterns of change over time in vital signs, 
insulin and other clinical labs, serum markers, and psycho-social outcomes (FACT-B) 
will also be analyzed similarly. If some of these measures are skewed, we will 
transform them (e.g., log) before the analyses. Finally, local recurrence, distant 
metastases, progression free survival, and overall survival will be analyzed via 
survival methods, specifically the Kaplan-Meier method and the logrank test. If 
sufficient events occur, we may assess the impact of various patient and 
clinical/treatment variables on these outcomes via Cox proportional hazards 
regression.  
Local recurrence, progression free survival, distant metastases and overall survival 
will be assessed and compared with historic controls using the Kaplan Meier method. 
Local recurrence, progression free survival, distant metastases and overall survival 
will be measured from the date of study enrollment to time of event. 
 Subject Population(s) for Analysis 
7.3
All subjects enrolled in the study who completed at least 4 food diaries per week 
during the diet modification phase will be used for analysis. 
 Safety and Adverse Events 
8
 Definitions 
8.1
 Adverse Event 
8.1.1
An adverse event (AE) is any symptom, sign, illness or experience that develops 
or worsens in severity during the course of the study.  Intercurrent illnesses or 
injuries should be regarded as adverse events.  Abnormal results of diagnostic 
procedures are considered to be adverse events if the abnormality: 
 
results in study withdrawal 
 
is associated with a serious adverse event 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
32 
 
is associated with clinical signs or symptoms 
 
leads to additional treatment or to further diagnostic tests 
 
is considered by the investigator to be of clinical significance 
 Serious Adverse Event 
8.1.2
Adverse events are classified as serious or non-serious.   
A serious adverse event is any AE that is:  
 
fatal 
 
life-threatening 
 
requires or prolongs hospital stay 
 
results in persistent or significant disability or incapacity 
 
a congenital anomaly or birth defect 
 
an important medical event 
Important medical events are those that may not be immediately life threatening, 
but are clearly of major clinical significance. They may jeopardize the subject, and 
may require intervention to prevent one of the other serious outcomes noted 
above.  For example, drug overdose or abuse, a seizure that did not result in in-
patient hospitalization, or intensive treatment of bronchospasm in an emergency 
department would typically be considered serious.  
All adverse events that do not meet any of the criteria for serious should be 
regarded as non-serious adverse events.  
 Adverse Event Reporting Period 
8.1.3
The study period during which adverse events must be reported is normally defined 
as the period from the initiation of any study procedures to the end of the study 
treatment follow-up.  For this study, the study treatment follow-up is defined as 30 
days following the last administration of study treatment.  
 Preexisting Condition 
8.1.4
A preexisting condition is one that is present at the start of the study.  A preexisting 
condition should be recorded as an adverse event if the frequency, intensity, or the 
character of the condition worsens during the study period. 
 General Physical Examination Findings 
8.1.5
At screening, any clinically significant abnormality should be recorded as a 
preexisting condition.  At the end of the study, any new clinically significant 
findings/abnormalities that meet the definition of an adverse event must also be 
recorded and documented as an adverse event.  
 Post-study Adverse Event 
8.1.6
All unresolved adverse events should be followed by the investigator until the 
events are resolved, the subject is lost to follow-up, or the adverse event is 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
33 
otherwise explained.  At the last scheduled visit, the investigator should instruct 
each subject to report any subsequent event(s) that the subject, or the subject’s 
personal physician, believes might reasonably be related to participation in this 
study.  The investigator should notify the study sponsor of any death or adverse 
event occurring at any time after a subject has discontinued or terminated study 
participation that may reasonably be related to this study.  The sponsor should also 
be notified if the investigator should become aware of the development of cancer or 
of a congenital anomaly in a subsequently conceived offspring of a subject that has 
participated in this study.  
 Abnormal Laboratory Values 
8.1.7
A clinical laboratory abnormality should be documented as an adverse event if any 
one of the following conditions is met:  
 
The laboratory abnormality is not otherwise refuted by a repeat test to confirm the 
abnormality 
 
The abnormality suggests a disease and/or organ toxicity 
 
The abnormality is of a degree that requires active management; e.g. change of 
dose, discontinuation of the drug, more frequent follow-up assessments, further 
diagnostic investigation, etc. 
 Hospitalization, Prolonged Hospitalization or Surgery 
8.1.8
Any adverse event that results in hospitalization or prolonged hospitalization should 
be documented and reported as a serious adverse event unless specifically 
instructed otherwise in this protocol.  Any condition responsible for surgery should 
be documented as an adverse event if the condition meets the criteria for and 
adverse event.  
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are 
reported as an adverse event in the following circumstances: 
 
Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for a preexisting condition.  Surgery should not be reported as an 
outcome of an adverse event if the purpose of the surgery was elective or diagnostic 
and the outcome was uneventful. 
 
Hospitalization or prolonged hospitalization required to allow efficacy measurement 
for the study. 
 
Hospitalization or prolonged hospitalization for therapy of the target disease of the 
study, unless it is a worsening or increase in frequency of hospital admissions as 
judged by the clinical investigator. 
 Recording of Adverse Events 
8.2
At each contact with the subject, the investigator must seek information on adverse 
events by specific questioning and, as appropriate, by examination.  Information on all 
adverse events should be recorded immediately in the source document, and also in 
the appropriate adverse event module of the case report form (CRF).  All clearly 
related signs, symptoms, and abnormal diagnostic procedures results should be 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
34 
recorded in the source document, though should be grouped under one diagnosis. 
All adverse events occurring during the study period must be recorded. The clinical 
course of each event should be followed until resolution, stabilization, or until it has 
been determined that the study treatment or participation is not the cause.  Serious 
adverse events that are still ongoing at the end of the study period must be followed 
up to determine the final outcome.  Any serious adverse event that occurs after the 
study period and is considered to be possibly related to the study treatment or study 
participation should be recorded and reported immediately. 
 Unblinding Procedures 
8.3
This is single arm study. There is no unblinding procedure. 
 Stopping Rules  
8.4
There will be no formal interim analyses for purposes of stopping the study early. 
However, descriptive analyses for monitoring accrual and study implementation will be 
carried out throughout the study. 
 Data and Safety Monitoring Plan 
8.5
It is the responsibility of the Principal Investigator to oversee the safety of the study at 
his/her site.  This safety monitoring will include careful assessment and appropriate 
reporting of adverse events as noted above, as well as the compliance and 
implementation of the KCC data and safety-monitoring plan.  Medical monitoring will 
include a regular assessment of the number and type of serious adverse events by 
both the assigned Medical Monitor and the KCC DSMC. 
 Medical Monitoring and AE/SAE Reporting 
8.5.1
A Medical Monitor is assigned to this study at the Thomas Jefferson University.  
This is a physician/pharmacist who is not directly involved in the trial, and is not 
currently collaborating with the sponsor/investigator on any other trial.  The role of 
the Medical Monitor is to review all reportable AEs/SAEs (in real-time) including 
grading, toxicity assignments, non-reportable AEs (quarterly), protocol 
violations/deviations, as well as all other safety data and activity data observed in 
the ongoing clinical trial occurring at Thomas Jefferson University. The Medical 
Monitor may recommend reporting of adverse events and relevant safety data, and 
may also recommend suspension or termination of the study to the DSMC and TJU 
IRB.   
Every KCC investigator initiated protocol includes requirements for reporting of 
adverse events based on CTC 4.0. All events are reported to the IRB and Medical 
Monitor using a password protected web-site. In addition all unexpected and 
serious adverse events (SAEs) are reported to the TJU IRB and to the Food and 
Drug Administration (FDA) if applicable. The investigator is required to submit all 
unexpected and serious adverse events to the TJU IRB and the Medical Monitor 
within the timeframes outlined in the below table. All AE/SAEs will be reported to 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
35 
the DSMC at the quarterly DSMC review meetings; however, if the Medical Monitor 
determines corrective action is necessary, an “ad hoc” DSMC meeting will be 
called. Fatal adverse events related to treatment which are unexpected must 
be reported within 24 hours to the TJU IRB and the DSMC. Fatalities not 
related to the study drug/device must be reported within 5 days. A summary of 
the reporting requirements for KCC investigator initiated Phase I and Phase II 
studies are presented below.  
 
 
Grade 1 
Grade 2 
Grade 2 
Grade 3 
Grade 3 
Grades 4 
and 5 
 
Unexpected 
and 
Expected 
Unexpected 
Expected 
Unexpected 
with 
Hospitalization 
Unexpected 
without 
Hospitalizatio
n 
Expected 
with 
Hospitalizatio
n 
Expected 
without 
Hospitalization 
Unexpecte
d and 
Expected 
Unrelated 
Unlikely 
Reviewed at 
Quarterly 
DSMC 
Meeting and 
IRB Annual 
Review 
Reviewed at 
Quarterly 
DSMC 
Meeting and 
IRB Annual 
Review 
Reviewed 
at 
Quarterly 
DSMC 
Meeting 
and IRB 
Annual 
Review 
5 Working 
Days 
Reviewed at 
Quarterly 
DSMC 
Meeting and 
IRB Annual 
Review 
5 Working 
Days 
Reviewed at 
Quarterly 
DSMC 
Meeting and 
IRB Annual 
Review 
Phase 1 -     
48 Hours   
(Death: 24 
Hours) 
 
Phase 2 -     
5 Working 
Days          
Possible 
Probable 
Definite 
Reviewed at 
Quarterly 
DSMC 
Meeting and 
IRB Annual 
Review 
5 working 
days 
Reviewed 
at 
Quarterly 
DSMC 
Meeting 
and IRB 
Annual 
Review 
48 Hours    
(Death: 24 
Hours) 
Phase 1 -         
48 Hours   
 
Phase 2 -         
5 Working 
Days 
48 Hours    
(Death: 24 
Hours) 
Reviewed at 
Quarterly 
DSMC 
Meeting and 
IRB Annual 
Review 
Phase 1 
and Phase 
2 -             
48 Hours      
(Death: 24 
Hours) 
 
**NOTE: This table is based on the NCI AE/SAE reporting Guidelines and the TJU 
IRB Policy and Procedures. Please follow the individual protocol AE/SAE reporting 
guidelines if more stringent reporting procedures are specified. 
 Data and Safety Monitoring Committee 
8.5.2
Data and Safety Monitoring Committee (DSMC) is the Data and Safety Monitoring 
Board (DSMB) for the KCC. The DSMC is a multidisciplinary committee charged 
with overseeing the monitoring of safety of participants in clinical trials, and the 
conduct, progress, validity, and integrity of the data for all clinical trials at the 
Thomas Jefferson University KCC. The committee meets quarterly to review the 
progress and safety of all active research protocols that are not monitored by 
another safety and data monitoring committee or board. 
 
The DSMC meets quarterly. Additional DSMC meetings are scheduled based on the 
nature and number of trials being monitored over a specified time period. The DSMC 
meets (by conference call) within 24 hours following the notification of an unexpected 
adverse event felt to be related to the study drug.  
 
Prior to each DSMC meeting, each board member, is provided a printout of all 
reported AEs and SAEs occurring during the reporting period for this clinical trial. 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
36 
The principal investigator provides a detailed and comprehensive narrative 
assessment of current adverse events to date, indicating their possible significance 
and whether these toxicities have affected the conduct of the trial. DSMC members 
are provided with the principal investigator’s assessment, a written report 
summarizing adverse events, safety data, and activity data observed during the 
specified time period described in each protocol, as well as recommendations from 
the Medical Monitor. A review of outcome results (response, toxicity and adverse 
events) and factors external to the study (such as scientific or therapeutic 
developments) is discussed, and the Committee votes on the status of each study.  
 
A summary of the board’s action is sent to each investigator, the CCRRC and TJU 
IRBs. The DSMC actions may include recommendations/requirements that will lead 
to improved patient safety and/or efficacy, significant benefits or risks that have 
developed, or other changes determined to be necessary. The DSMC may also take 
note of slow accrual or lack of scientific progress, and refer such issues to the 
CCRRC. The DSMC provides the investigator with the rationale for any decision 
made.  
 Data Handling and Record Keeping 
9
 Confidentiality 
9.1
Information about study subjects will be kept confidential and managed according to 
the requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA).  Those regulations require a signed subject authorization informing the 
subject of the following:  
 
What protected health information (PHI) will be collected from subjects in this study 
 
Who will have access to that information and why 
 
Who will use or disclose that information 
 
The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, 
by regulation, retains the ability to use all information collected prior to the revocation 
of subject authorization.  For subjects that have revoked authorization to collect or use 
PHI, attempts should be made to obtain permission to collect at least vital status (i.e. 
that the subject is alive) at the end of their scheduled study period. 
 Source Documents 
9.2
Source data is all information, original records of clinical findings, observations, or 
other activities in a clinical trial necessary for the reconstruction and evaluation of the 
trial. Source data are contained in source documents.  Examples of these original 
documents, and data records include: hospital records, clinical and office charts, 
laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy 
dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and 
records kept at the pharmacy, at the laboratories, and at medico-technical 
departments involved in the clinical trial. 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
37 
 Case Report Forms 
9.3
The study case report form (CRF) is the primary data collection instrument for the 
study. All data requested on the CRF must be recorded. All missing data must be 
explained. If a space on the CRF is left blank because the procedure was not done or 
the question was not asked, write “N/D”. If the item is not applicable to the individual 
case, write “N/A”. All entries should be printed legibly in black ink. If any entry error 
has been made, to correct such an error, draw a single straight line through the 
incorrect entry and enter the correct data above it. All such changes must be initialed 
and dated. DO NOT ERASE OR WHITE OUT ERRORS. For clarification of illegible or 
uncertain entries, print the clarification above the item, then initial and date it. 
CRFs are found in the Appendix VII. 
 Records Retention 
9.4
It is the investigator’s responsibility to retain study essential documents for at least 2 
years after the last approval of a marketing application in their country and until there 
are no pending or contemplated marketing applications in their country or at least 2 
years have elapsed since the trial began. 
 STUDY MONITORING, AUDITING, AND INSPECTING 
10
 Study Monitoring Plan 
10.1
The investigator will allocate adequate time for monitoring activities. The Investigator 
will also ensure that the medical monitor or other compliance or quality assurance 
reviewer is given access to all the above noted study-related documents and study 
related facilities (e.g. pharmacy, diagnostic laboratory, etc.), and has adequate space 
to conduct the monitoring visit. 
 Auditing and Inspecting 
10.2
The investigator will permit study-related monitoring, audits, and inspections by the 
IRB, the funding sponsor, government regulatory bodies, and University compliance 
and quality assurance groups of all study related documents (e.g. source documents, 
regulatory documents, data collection instruments, study data etc.). The investigator 
will ensure the capability for inspections of applicable study-related facilities (e.g. 
pharmacy, diagnostic laboratory, etc.). 
Participation as an investigator in this study implies acceptance of potential inspection 
by government regulatory authorities and applicable University compliance and quality 
assurance offices. 
 Independent External and Internal Audits  
10.2.1
In addition to review by the DSMC, all studies initiated by KCC investigators are 
audited by an independent auditor once they have achieved 10% of target accrual. 
However, a study can be audited at any time based on recommendations by the 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
38 
IRB, DSMC, CCRRC and/or the Director of Clinical Investigations, KCC. Studies 
are re-audited once they have achieved 50% of target accrual. Special audits may 
be recommended by the IRB, DSMC or CCRRC based on prior findings, 
allegations of scientific misconduct and where significant irregularities are found 
through quality control procedures. Any irregularities identified as part of this 
process would result in a full audit of that study.  
In addition to the audits at 10 and 50%, the CRMO randomly audits at least 10 
percent of all patients entered into therapeutic KCC trials and other trials as 
necessary, on at least a bi-annual basis, to verify that there is a signed and dated 
patient consent form, the patient has met the eligibility criteria, and that SAEs are 
documented and reported to the TJU IRB.  
All audit reports are submitted to the DSMC for review and action (when 
appropriate). A copy of this report and recommended DSMC action is sent to the 
CCRRC and TJU IRB. The committee regards the scientific review process as 
dynamic and constructive rather than punitive. The review process is designed to 
assist Principal Investigators in ensuring the safety of study subjects and the 
adequacy and accuracy of any data generated. The TJU IRB may, based on the 
DSMC and auditor’s recommendation, suspend or terminate the trial.  
 Ethical Considerations 
11
This study is to be conducted according to US and international standards of Good 
Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization 
guidelines), applicable government regulations and Institutional research policies and 
procedures. 
This protocol and any amendments will be submitted to a properly constituted 
independent Institutional Review Board (IRB), in agreement with local legal 
prescriptions, for formal approval of the study conduct.  The decision of the IRB 
concerning the conduct of the study will be made in writing to the investigator before 
commencement of this study.   
All subjects for this study will be provided a consent form that is compliant with local and 
federal regulations, describing this study and providing sufficient information for subjects 
to make an informed decision about their participation in this study.  See Attachment for 
a copy of the Subject Informed Consent Form.  This consent form will be submitted with 
the protocol for review and approval by the IRB for the study.  The formal consent of a 
subject, using the IRB-approved consent form, must be obtained before that subject is 
submitted to any study procedure.  This consent form must be signed by the subject or 
legally acceptable surrogate, and the investigator-designated research professional 
obtaining the consent.  
 Study Finances 
12
 Funding Source 
12.1
This study is financed through a generous pilot grant from the Ladies of Port 

 
 
 
 
12G.616 Protocol v4.2 (04Jan2016) 
39 
Richmond. It is also financed in part by the Kimmel Cancer Center’s NCI Cancer 
Center Support Grant P30 CA56036. 
 Conflict of Interest 
12.2
Any investigator who has a conflict of interest with this study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by their institution, etc.) 
must have the conflict reviewed by a properly constituted Conflict of Interest 
Committee with a Committee-sanctioned conflict management plan that has been 
reviewed and approved by the study sponsor prior to participation in this study.  All 
Jefferson University Investigators will follow the TJU Conflicts of Interest Policy for 
Employees (107.03). 
 Publication Plan 
13
All investigators involved in the portion of the trial being published will review 
manuscripts prior to publication. The Principal Investigator will be ultimately responsible 
for the content of all manuscripts.  
 Specimen Banking 
14
Tissue and blood specimen banking is included in this protocol. Tissue and blood 
specimens will be stored in a secure -70° freezer in the Bodine Cancer Center.  
Specimen collections will be performed on consented patients. Please see Appendix VI 
for detailed information on schedule, amount, storage and shipping requirement. 
 References 
15
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Longo VD, Fontana L. Calorie restriction and cancer prevention: metabolic 
and molecular mechanisms. Trends Pharmacol Sci. Feb;31(2):89-98. 
2. 
Hursting SD, Lavigne JA, Berrigan D, Perkins SN, Barrett JC. Calorie 
restriction, aging, and cancer prevention: mechanisms of action and 
applicability to humans. Annu Rev Med. 2003;54:131-152. 
3. 
Rous P. The influence of diet on transplanted and spontaneous mouse 
tumors. J. Exp. Med. 1909;20(431). 
4. 
Tannenbaum A. Effects of Varying Caloric Intake Upon Tumor Incidence 
and Tumor Growth. Annals of the New Yrok Acedemy of Sciences. 15 Dec 
2006 2006;49(1). 
5. 
Berrigan D, Perkins SN, Haines DC, Hursting SD. Adult-onset calorie 
restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. 
Carcinogenesis. May 2002;23(5):817-822. 
6. 
Zhu Z, Jiang W, Thompson HJ. Effect of energy restriction on tissue size 
regulation during chemically induced mammary carcinogenesis. 
Carcinogenesis. Sep 1999;20(9):1721-1726. 
7. 
Lok E, Scott FW, Mongeau R, Nera EA, Malcolm S, Clayson DB. Calorie 
restriction and cellular proliferation in various tissues of the female Swiss 
Webster mouse. Cancer Lett. May 15 1990;51(1):67-73. 

 
 
 
 
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8. 
Grasl-Kraupp B, Bursch W, Ruttkay-Nedecky B, Wagner A, Lauer B, Schulte-
Hermann R. Food restriction eliminates preneoplastic cells through apoptosis 
and antagonizes carcinogenesis in rat liver. Proc Natl Acad Sci U S A. Oct 11 
1994;91(21):9995-9999. 
9. 
Turner BC, Haffty BG, Narayanan L, et al. Insulin-like growth factor-I receptor 
overexpression mediates cellular radioresistance and local breast cancer 
recurrence after lumpectomy and radiation. Cancer Res. Aug 1 
1997;57(15):3079-3083. 
10. 
Perer ES, Madan AK, Shurin A, et al. Insulin-like growth factor I receptor 
antagonism augments response to chemoradiation therapy in colon cancer 
cells. J Surg Res. Nov 2000;94(1):1-5. 
11. 
Donohoe CL, Doyle SL, Reynolds JV. Visceral adiposity, insulin resistance 
and cancer risk. Diabetol Metab Syndr.3:12. 
12. 
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin 
resistance and type 2 diabetes. Nature. Dec 14 2006;444(7121):840-846. 
13. 
Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella E, Hwang 
D, Cohen P, Bianchi G, Longo VD. Reduced levels of IGF-1 
mediate differential protection of normal and cancer cells in response to 
fasting and improve chemotherapeutic index. Cancer Res. 2010 Feb 
15;70(4):1564-72. 
14. 
Safdie F, Brandhorst S, Wei M, Wang W, Lee C, Hwang S, Conti PS, Chen 
TC, Longo VD. Fasting enhances the response of glioma to chemo- and 
radiotherapy. PLoS One. 2012;7(9):e44603. 
15. 
National Institutes of Health. http://www.clincaltrials.gov.  
16. 
Arguin, H., I. J. Dionne, et al. (2012). Short- and long-term effects of 
continuous versus intermittent restrictive diet approaches on body 
composition and the metabolic profile in overweight and obese 
postmenopausal women: a pilot study. Menopause; 19(8): 870-876. 
 
 

 
 
 
 
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 APPENDICES 
16
 
 

 
 
 
 
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Appendix I: Patient Thank You Letter  
 
This is a template to prepare a letter thanking the patient for enrolling in this trial. The 
template is intended as a guide and can be tailored to each patient’s situation. This is to 
increase the awareness of the importance of clinical trials and improve accrual and 
follow-through.  
 
[PATIENT NAME]   
 
 
 
 
 
 
[DATE] 
[PATIENT ADDRESS] 
 
Dear [PATIENT SALUTATION], 
 
Thank you for agreeing to take part in this important research study. Many questions 
remain unanswered in cancer. With the help of people like you who participate in clinical 
trials, we will achieve our goal of effectively treating and ultimately curing cancer. 
 
We believe you will receive high quality, complete care. I and my research staff will 
maintain very close contact with you. This will allow me to provide you with the best 
care while learning as much as possible to help you and other patients. 
 
On behalf of Thomas Jefferson University, we thank you again and look forward to 
helping you. 
 
Sincerely, 
[PHYSICIAN NAME] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Appendix II: Karnofsky Performance Scale 
 
Able to carry on normal activity and to work; no 
special care needed. 
  100   Normal no complaints; no evidence of 
disease. 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease. 
80 
Normal activity with effort; some signs 
or symptoms of disease. 
Unable to work; able to live at home and care for 
most personal needs; varying amount of 
assistance needed. 
70 
Cares for self; unable to carry on 
normal activity or to do active work. 
60 
Requires occasional assistance, but is 
able to care for most of his personal 
needs. 
50 
Requires considerable assistance and 
frequent medical care. 
Unable to care for self; requires equivalent of 
institutional or hospital care; disease may be 
progressing rapidly. 
40 
Disabled; requires special care and 
assistance. 
30 
Severely disabled; hospital admission 
is indicated although death not 
imminent. 
20 
Very sick; hospital admission 
necessary; active supportive treatment 
necessary. 
10 
Moribund; fatal processes progressing 
rapidly. 
0 
Dead 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Appendix III: 
Common Toxicity Criteria Version 4.0 
http://ctep.cancer.gov/reporting/ctc.html 
 
 
 

 
 
 
 
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Appendix IV: Visit Schedule  
(please refer to appendix VI for blood specimen banking schedule) 

 
 
 
 
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Appendix V. Behavioral Modification Worksheets 
 
Initially patients will be counseled on eating healthy and dietary modification before 
beginning their diet. They will complete the worksheets labeled “Be a Fat Detective”, 
“Eating Less Fat” and “Healthy Eating” during this first week. 
 

 
 
 
 
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Patients will complete this worksheet on environmental cues during week 1 of 
radiation/week 3 of diet. 
 

 
 
 
 
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Patients will complete this worksheet on problem solving during week 2 of 
radiation/week 4 of their diet. 
 

 
 
 
 
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Patients will complete this worksheet on dining out during week 3 of 
radiation/week 5 of diet. 
 

 
 
 
 
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Patients will complete this worksheet on negative thoughts during week 4 of 
radiation/week 6 of diet. 
 

 
 
 
 
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Patients will complete this worksheet on social cues during week 5 of 
radiation/week 7 of diet. 
 

 
 
 
 
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Patients will go through the following worksheet during week 6 of radiation/week 
8 of diet. 
 

 
 
 
 
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Prior to the final week of their diet, patients will go through this worksheet on 
staying motivated. 
 

 
 
 
 
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Appendix VI. Blood/Tissue Specimen Collection and Banking 
  
Blood 
1. 
Blood specimen collections will be performed on each patient. 
2. 
Timing: baseline at radiation simulation visit, conclusion of diet and 4 weeks after 
radiation. 
3. 
Collection: Each time, 20-30 cc blood will be collected using two sodium heparin 
vacutainer tubes. 
4. 
Sample preparation: Blood specimens collected from Thomas Jefferson 
University should be processed locally the same day of collection. Processed 
samples (serum and plasma) should be given to Dr. Simone or member of her 
laboratory. 
5. 
Process: All blood specimens collected will be processed locally within 24 hr of 
collection. The blood specimens will be processed for plasma and serum. 
6. 
Storage: Plasma specimens and serum will be stored in liquid nitrogen or a -70-
80C freezer 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Appendix VII. Case Report Forms 
 
THOMAS JEFFERSON UNIVERSITY HOSPITAL 
DEPARTMENT OF RADIATION ONCOLOGY 
 
CAREFOR Study: A Feasibility Pilot Trial Evaluating Caloric Restriction for Oncology Research 
in Early Stage Breast Cancer Patients 
 
REGISTRATION FORM 
 
Patient’s Initials 
      Case#   
 
          Dose Level 
 
 
     
 
 
MR# 
 
 
 
 
                     Date of birth 
 
 
 
 
 
 
Address__________________________________________________________________ 
 
_________________________________________________________________________ 
 
 
Telephone_________________________________ 
 
 
 
Sex 
 
 
 
Race_______________ Ethnicity ___________________ 
 
Insurance________________________________ 
 
 
Radiation Oncologist:  
 
 
 
 
 
 
Medical Oncologist: 
 
 
 
 
 
 
 
Resident: 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature_________________________________________ 
Date______________ 
 
 
 
 

 
 
 
 
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CAREFOR Study Case Report Form (CRF)—Screening Visit 
Date of Screening: 
 
 
 
 
 
Patient Demographics 
Age: 
 
 
Race: 
 
 
 
 
 
 
 
 
 
Current Address (for mailing purposes):  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Emergency Contact: 
 
 
 
 
 
 
 
 
 
 
 
 
Marital Status:  
 
 
 
 
 
 
 
 
Highest Education Level Completed: 
 
 
 
 
 
 
 
Past Medical History and Relevant Clinical Information 
Date of Diagnosis: 
 
          
How was the mass found?  
 MMG 
 SBE 
 Physician Exam 
 Other:  
 
 
 
 
Date of most recent mammogram: 
 
 
 
Side of Breast Mass (L v. R): 
 
 
 
Previous History of Breast Cancer: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Family History of Breast Cancer:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If applicable, what treatment was received for previous breast cancer:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 Previous History of any 
other malignancy (include dates of diagnosis and NED date): 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is this patient a candidate for breast conservation? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Oral 
Contraceptive Use (current or past):  Y  or  N 
Hormone Replacement Use:  Y  or  N 
Date of last period 
 
 
 
Age at menarche: 
 
 
 
 
 
Gravida/Para:  
 
 
 
 
 
 
 
Previous diagnosis of any of the following: 
 
Unstable Angina 
 
Coronary Artery Disease 

 
 
 
 
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Myocardial Infarct, if yes please indicate date of event:  
 
 
 
 
CHF 
 
Valvular Disease 
 
Arrythmias/Pacemaker Placement 
 
Diabetes 
 
Severe Asthma 
 
Autoimmune Disorder (specifically SLE, scleroderma, dermatomyositis) 
 
Any Disease Requiring Chronic Steroid Use 
Inflammatory Bowel Disease 
Celiac Disease 
Chronic Pancreatitis 
Chronic Diarrhea or Vomiting 
Active Eating Disorder 
Renal Failure or CKD 
Pituitary Secreting Tumor 
HIV Positive Status or AIDS including any AIDS defining illness 
Hepatic Insufficiency 
 
Recent hospitalization (within the last 6 months, include diagnosis and length of stay): 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recent Weight Loss (include baseline weight and pounds lost):  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical History 
Please indicate any major surgeries, the date or at least the year of the surgery and whether or not 
there were any post-op complications: 
Surgery Date 
 
Pre-op Diagnosis 
 
Post-Op Complications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pertinent Social History 
Current Occupation: 
 
 
 
 
 
 
 
 
 
 
Habitation Status (alone or with family):  
 
 
 
 
 
 
Alcohol Use: 
 
 
 
 
 
 
 
 
 
 
 
Previous of Current Use of Illicit Drugs:  
 
 
 
 
 
 
Smoker (indicate pack/year for current or past and year of cessation): 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Currently Sexually Active:  Y  or  N 

 
 
 
 
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If yes, what type of contraception is being used? 
 
 
 
 
 
If no contraception, is the patient willing to use contraception for the duration of the study/treatment 
period?  
 
 
 
 
 
 
 
 
 
Allergies: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Current Medications (indicate dose, route, frequency and start date): 
Medication 
 
Dose 
 
Route  
Frequency 
 
Start Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Physical Examination 
Height:  
 
 
Weight: 
 
BMI: 
 
 
 
 
 
Karnofsky Performance Status: 
Please assess the patient’s performance status based on the table provided. Circle the most appropriate 
functional capacity. 
Able to carry on normal activity and to work; no 
special care needed. 
  100   Normal no complaints; no evidence of 
disease. 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease. 
80 
Normal activity with effort; some signs 
or symptoms of disease. 
Unable to work; able to live at home and care for 
most personal needs; varying amount of 
assistance needed. 
70 
Cares for self; unable to carry on 
normal activity or to do active work. 
60 
Requires occasional assistance, but is 
able to care for most of his personal 
needs. 
50 
Requires considerable assistance and 
frequent medical care. 
Unable to care for self; requires equivalent of 
institutional or hospital care; disease may be 
progressing rapidly. 
40 
Disabled; requires special care and 
assistance. 
30 
Severely disabled; hospital admission 
is indicated although death not 
imminent. 
20 
Very sick; hospital admission 
necessary; active supportive treatment 
necessary. 
10 
Moribund; fatal processes progressing 
rapidly. 
0 
Dead 
 
 
 
 

 
 
 
 
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Thomas Jefferson University 
Kimmel Cancer Center 
 
CAREFOR Inclusion/Exclusion Criteria Checklist 
 
Inclusion Criteria: 
Patients must meet all of the following criteria in order to be considered for entry into the 
CAREFOR trial. 
 Pathologically confirmed diagnosis of DCIS or invasive breast cancer 
 Female patient, 18 years or older 
 Candidate for breast conservation 
 Karnofsky performance status at least 80%  
 Negative serum beta-hCG if appropriate 
 Willing to use contraception, not sexually active or post-menopausal 
 BMI > 21 
 Weight > 100lbs 
 
Exclusion Criteria: 
In addition to meeting inclusion criteria, patients are ineligible for enrollment if any of the 
following exclusion criteria are met. 
 Intentional weight loss > 10% of total body weight within the last 3 months prior to 
trial enrollment. 
 Prior non-breast invasive malignancy, unless free of disease for at least 1 year prior to 
trial enrollment. 
 Two or more breast cancers not resectable through a single lumpectomy site. 
 Non-epithelial breast malignancies such as sarcoma or lymphoma. 
 Prior radiotherapy to ipsilateral breast that would result in overlapping radiation fields. 
 Severe, active comorbidities to include any one of the following:  
 
Unstable angina or CHF requiring hospitalization in the last 6 months 
 
COPD exacerbation requiring hospitalization within 30 days of registration 
 
Transmural myocardial infarct in the past 6 months 
 
Acute bacterial or fungal infection requiring IV antibiotics at the time of 
registration 

 
 
 
 
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 
Hepatic insufficiency resulting in clinical jaundice 
 
AIDS or HIV positive according to CDC guidelines   
 Active systemic lupus erythematosus, scleroderma or dermatomyositis with rash. 
 Medical or psychiatric condition preventing the patient from providing informed consent or 
from adhering to diet guidelines. 
 Currently taking diet supplements 
 Active gastrointestinal/malabsorption syndrome to include: 
 Inflammatory Bowel Disease 
 Celiac Disease 
 Chronic Pancreatitis 
 Chronic Diarrhea or Vomiting 
 Active Eating Disorder 
 Currently using steroids 
   
 Active/history of substance abuse or dependency to include prescription or illicit drugs 
as well as alcohol. 
 Decisionally impaired patients. 
 
 
 
 

 
 
 
 
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Checklist for Screening Visit: 
 
Informed Consent for Trial Obtained 
 
All Sections of CRF Completed 
 
Inclusion/Exclusion Criteria Evaluated 
 
Blood draw: Beta-HCG 
 
H&P; Performance Status 
 
Weight, BMI 
 
Based on screening patient appears eligible 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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CAREFOR Study Case Report Form (CRF)—Radiation Treatment Planning Visit 
Date of Sim Visit: 
 
 
 
 
 
Lumpectomy Details 
Please indicate the actual date of the lumpectomy, whether or not there were any post-op 
complications and the status of the Path report: 
Surgery Date 
 
Pre-op Diagnosis 
 
Post-Op Complications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Path Report Received?  Y  or  N 
Attach a copy of the Path Report to this visit. 
 
Verify Allergies: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Changes to Current Medications (indicate dose, route, frequency and start date): 
Medication 
 
Dose 
 
Route  
Frequency 
 
Start Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Physical Examination 
Height:  
 
 
Weight: 
 
BMI: 
 
 
 
 
Vital Signs: 
BP: 
 
    HR:  
 
Temp:  
 
RR: 
 
 
Caliper Measurements:  
 
 
 
 
 
 
 
 
 
Bioimpedance Measurement: 
 
 
 
 
 
 
 
 
 
Please indicate the status (normal or abnormal) of each system listed below. If abnormal, please make 
notes. Give detailed description of breast exam in the notes section. 
Organ System  
 
Status  
 
 
Notes 
CVS 
 
 
Normal Abnormal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulm 
 
 
Normal Abnormal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GI 
 
 
Normal Abnormal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neuro  
 
Normal Abnormal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Breast  
 
Normal Abnormal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CTCAE v4.0 Evaluation 
Please evaluate the patient at baseline for comparison during and post-radiation. 
 
 
 

 
 
 
 
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Checklist for Sim Visit: 
 
Pathology Report Obtained and Attached 
 
Baseline Labs: CBC w/diff, CMP, HbA1c 
Serum: IGF-1, adiponectin, leptin, estradiol, triglycerides, 
ESR, insulin, glucose 
 
Blood Sample sent to Dr. Simone’s lab for further analysis 
 
All Sections of CRF Completed 
 
FACT-B Completed by patient 
 
Weight, BMI, Body fat persent, bioimpedance 
 
Food diaries collected at this visit 
 
Dietary Counseling for caloric restriction diet alterations 
 
 
Please attach a copy of patient’s labs when available. 
Please attach a copy of food diary. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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CAREFOR Study Case Report Form (CRF)—Diet Support Visit: Day 7 of CR Diet 
Date of Visit: 
 
 
 
 
 
Changes to Current Medications (indicate dose, route, frequency and start date): 
Medication 
 
Dose 
 
Route  
Frequency 
 
Start Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height:  
 
 
Weight: 
 
BMI: 
 
 
 
 
Vital Signs: 
BP: 
 
    HR:  
 
Temp:  
 
RR: 
 
 
 
Food Diary Received and Completed:  Y  or  N 
If no, must collect at next visit. 
 
 
 
 

 
 
 
 
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Checklist for D7 Visit: 
 
All Sections of CRF Completed 
 
Weight, BMI 
 
Food diary collected at this visit 
 
 
Please attach a copy of food diary. 
24 hour recall of food intake: 
 
Meal 
   
 
Food Type 
 
 
 
 
Amount 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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CAREFOR Study Case Report Form (CRF)—Diet Support Visit: Day 14 of CR Diet 
Date of Visit: 
 
 
 
 
 
Changes to Current Medications (indicate dose, route, frequency and start date): 
Medication 
 
Dose 
 
Route  
Frequency 
 
Start Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height:  
 
 
Weight: 
 
BMI: 
 
 
 
 
Vital Signs: 
BP: 
 
    HR:  
 
Temp:  
 
RR: 
 
 
 
Food Diary Received and Completed:  Y  or  N 
If no, must collect at next visit. 
 
 
 

 
 
 
 
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Checklist for D14 Visit: 
 
All Sections of CRF Completed 
 
Weight, BMI 
 
Food diary collected at this visit 
 
 
Please attach a copy of food diary. 
24 hour recall of food intake: 
 
Meal 
   
 
Food Type 
 
 
 
 
Amount 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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CAREFOR Study Case Report Form (CRF)—Radiation Treatment 
Date of Visit: 
 
 
 
 
Weeks of Radiation Completed: 
 
 
 
Changes to Current Medications (indicate dose, route, frequency and start date): 
Medication 
 
Dose 
 
Route  
Frequency 
 
Start Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Food Diary Received and Completed:  Y  or  N          If no, must collect at next visit. 
 
Physical Examination 
Height:  
 
 
Weight: 
 
BMI: 
 
 
 
 
Vital Signs: 
BP: 
 
    HR:  
 
Temp:  
 
RR: 
 
 
 
Please indicate the status (normal or abnormal) of each system listed below. If abnormal, please make 
notes. Give detailed description of breast exam in the notes section. 
 
Breast  
 
Normal Abnormal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema 
 
Mild  
Moderate       Severe 
Hyperpigmentation 
Mild  
Moderate       Severe 
Desquamation  
Yes 
No 
Dermatitis 
 
Yes  
No 
Edema  
 
Yes 
 No 
 
 
 
 
 
 
 
 

 
 
 
 
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CTCAE v4.0 Evaluation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Checklist for Visit: 
 
 
All Sections of CRF Completed 
 

 
 
 
 
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Weight, BMI 
 
Food diary collected at this visit 
 
Dietary Counseling for caloric restriction diet alterations 
 
 
Please attach a copy of patient’s labs when available. 
Please attach a copy of food diary. 
 
24 hour recall of food intake: 
 
Meal 
   
 
Food Type 
 
 
 
 
Amount 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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CAREFOR Study Case Report Form (CRF)—Post RT Visit 1 
Date of Visit: 
 
 
 
 
Date Radiation Completed: 
 
 
 
Height:  
 
 
Weight: 
 
BMI: 
 
 
 
 
Vital Signs: 
BP: 
 
    HR:  
 
Temp:  
 
RR: 
 
 
 
Changes to Current Medications (indicate dose, route, frequency and start date): 
Medication 
 
Dose 
 
Route  
Frequency 
 
Start Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Food Diary Received and Completed:  Y  or  N               If no, must collect at next visit. 
 
Breast Exam 
 
Normal  Abnormal 
 
Notes:  
 
 
 
                                                                                                           
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema 
 
Mild  
Moderate       Severe 
Hyperpigmentation 
Mild  
Moderate       Severe 
Desquamation  
Yes 
No 
Dermatitis 
 
Yes  
No 
Edema  
 
Yes 
 No 
 
 
 
 
 
CTCAE v4.0 Evaluation 
 
 
 
 
 
 
 
 

 
 
 
 
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Checklist for Visit: 
 
 
All Sections of CRF Completed 
 
Weight, BMI 
 
Food diary collected at this visit 
 
 
Please attach a copy of patient’s labs when available. 
Please attach a copy of food diary. 
 
24 hour recall of food intake: 
 
Meal 
   
 
Food Type 
 
 
 
 
Amount 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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CAREFOR Study Case Report Form (CRF)—Post RT Visit 2 
Date of Visit: 
 
 
 
 
Date Radiation Completed: 
 
 
 
Height:  
 
 
Weight: 
 
BMI: 
 
 
 
 
Vital Signs: 
BP: 
 
    HR:  
 
Temp:  
 
RR: 
 
 
Caliper Measurements:  
 
 
 
 
 
 
 
 
 
Bioimpedance Measurement: 
 
 
 
 
 
 
 
 
 
Changes to Current Medications (indicate dose, route, frequency and start date): 
Medication 
 
Dose 
 
Route  
Frequency 
 
Start Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Food Diary Received and Completed:  Y  or  N 
If no, must collect at next visit. 
 
Breast Exam 
 
Normal  Abnormal 
 
Notes:  
 
 
 
                                                                                                           
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema 
 
Mild  
Moderate       Severe 
Hyperpigmentation 
Mild  
Moderate       Severe 
Desquamation  
Yes 
No 
Dermatitis 
 
Yes  
No 
Edema  
 
Yes 
 No 
 
 
CTCAE v4.0 Evaluation 
 

 
 
 
 
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Checklist for Visit: 
Completion Labs: CBC w/diff, CMP, HbA1c 
Serum: IGF-1, adiponectin, leptin, estradiol, triglycerides, 
ESR, insulin, glucose 
 
Blood Sample sent to Dr. Simone’s lab for further analysis 
 
All Sections of CRF Completed 
 
FACT-B Completed by patient 
 
Weight, BMI, Body fat percent, bioimpedance 
 
Food diary collected at this visit 
 
 
Please attach a copy of patient’s labs when available. 
Please attach a copy of food diary. 
 
24 hour recall of food intake: 
 
Meal 
   
 
Food Type 
 
 
 
 
Amount 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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CAREFOR Study Case Report Form (CRF)—Follow-up Visit 
Date of Visit: 
 
 
 
 
 
Physical Examination 
Height:  
 
 
Weight: 
 
BMI: 
 
 
 
 
Vital Signs: 
BP: 
 
    HR:  
 
Temp:  
 
RR: 
 
 
Caliper Measurements:  
 
 
 
 
 
 
 
 
 
Bioimpedance Measurement: 
 
 
 
 
 
 
 
 
 
Changes to Current Medications (indicate dose, route, frequency and start date): 
Medication 
 
Dose 
 
Route  
Frequency 
 
Start Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Please indicate the status (normal or abnormal) of each system listed below. If abnormal, please make 
notes. Give detailed description of breast exam in the notes section. 
Breast Exam 
 
Normal  Abnormal 
 
Notes:  
 
 
 
                                                                                                           
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema 
 
Mild  
Moderate       Severe 
Hyperpigmentation 
Mild  
Moderate       Severe 
Desquamation  
Yes 
No 
Dermatitis 
 
Yes  
No 
Edema  
 
Yes 
 No 
 
CTCAE v4.0 Evaluation 
 
 
 
 
 

 
 
 
 
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Checklist for Follow-up Visit: 
 
Follow-up Labs: CBC w/diff, CMP, HbA1c 
Serum: IGF-1, adiponectin, leptin, estradiol, triglycerides, 
ESR, insulin, glucose 
 
Blood Sample sent to Dr. Simone’s lab for further analysis 
 
All Sections of CRF Completed 
 
FACT-B Completed by patient 
 
Weight, BMI, Body fat percent, bioimpedance 
 
Food diaries collected at this visit 
 
 
Please attach a copy of patient’s labs when available. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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THOMAS JEFFERSON UNIVERSITY HOSPITAL 
DEPARTMENT OF RADIATION ONCOLOGY 
 
CAREFOR Study: A Feasibility Pilot Trial Evaluating Caloric Restriction for Oncology Research 
in Early Stage Breast Cancer Patients 
 
WITHDRAWAL FORM 
 
Patient Initials ________       MR# _______________ 
 
     Patient ID # _________ 
 
 
Please initial below: 
 
 
_____ I no longer wish to participate in this research study. 
 
 
_____ I am withdrawing from the study treatment, but I agree to the research coordinator 
following up with me periodically to see how I am doing. 
 
 
 
Please sign below: 
 
 
Patient: ____________________________________  Date: ___________ 
 
 
Witnessed By: _______________________________ Date: ___________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Thomas Jefferson University Hospital 
Department of Radiation Oncology 
CAREFOR Study 
 
 
Current Medication Flowsheet  
 
 
Date 
Started 
Medication 
Indication 
Route 
Frequency 
Dose 
Date Stopped 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Allergies: 
 
 
 
 
 
Physician Signature: ___________________________________   Date:____________ 
 
 
 
 
 
Study :                                       Patient Case No.                         Time Frame/Cycle #    
 
                                                                              Intermittent RT 
(circle one): Y or N, N/A 

 
 
 
 
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Appendix VIII. Recruitment Flyer 
 
 
 
 
 
Appendix IX. Food Diaries 
 
Printed Food Diary: 
 
 
 
Online Food Diary: 
Accessible at: http://www.myfitnesspal.com 
 
 
 
 
 

 
 
 
 
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Appendix X. 
Thomas Jefferson University 
Kimmel Cancer Center 
 
CAREFOR Inclusion/Exclusion Criteria Checklist 
 
Inclusion Criteria: 
Patients must meet all of the following criteria in order to be considered for entry into the 
CAREFOR trial. 
  Pathologically proven diagnosis of DCIS or invasive breast cancer  
  Ability to have breast conservation as determined by the judgment of the 
radiation oncologist 
  The patient must be female 
  Age ≥ 18 
 If multifocal breast cancer, then it must be able to be resected through a single 
lumpectomy incision  
  Appropriate stage for protocol entry, including no clinical evidence for distant 
metastases, based upon the following minimum diagnostic workup: 
  History/physical examination, including breast exam and documentation of 
weight and Karnofsky Performance Status of 80-100% at study entry.  
  Women of childbearing potential must have a negative serum pregnancy test 
within 14 days of study entry 
  Women of childbearing potential must be non-pregnant and non-lactating and 
willing to use medically acceptable form of contraception during radiation therapy 
  Patient must capable of and provide study specific informed consent prior to 
study entry 
  BMI ≥21  
  Weight ≥100lbs   
  No prior history of non-breast invasive malignancies in the past 1year  
  Patient must not have any of the following severe, active co-morbidity, defined as 
follows: 
o Unstable angina and/or congestive heart failure requiring hospitalization 
within the last 6 months 
o Transmural myocardial infarction within the last 6 months 
o Acute bacterial or fungal infection requiring intravenous antibiotics at the 
time of registration; 
o Chronic Obstructive Pulmonary Disease exacerbation or other respiratory 
illness requiring hospitalization or precluding study therapy within 30 days 
before registration; 

 
 
 
 
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o Hepatic insufficiency resulting in clinical jaundice and/or coagulation 
defects; note, however,that laboratory tests for liver function and 
coagulation parameters are not required for entry into this protocol 
o Acquired Immune Deficiency Syndrome (AIDS) or HIV positive based upon 
current CDC definition; note,however, that HIV testing is not required for 
entry into this protocol. The need to exclude patients with AIDS or HIV 
from this protocol is necessary because anti-retrivirals may alter patient 
metabolism. 
 Patient must not have active systemic lupus, erythematosus, or any history of 
scleroderma, dermatomyositis with active rash 
 No prior radiotherapy to the ipsilateral breast or prior radiation to the region of the 
breast that would result in overlap of radiation therapy fields 
 Patient may not have any active Gastrointestinal/Malabsorption disorder at the 
discretion of the Principal Investigator 
o Inflammatory Bowel Disease 
o Celiac Disease 
o Chronic Pancreatitis 
o Chronic Diarrhea or Vomiting 
o Active Eating Disorder 
  
 Not currently taking steroids 
 No history of or current active drug/alcohol dependence.   
 No patients with decisional impairment. 
 
Exclusion Criteria 
  Patient is not a candidate for breast conservation. 
  Patient is male. 
  Age <18 years 
 Patient has evidence of distant metastases 
 Karnofsky Performance Status less than 80% within 60 days prior to 
study. 
 Ipsilateral mammogram done greater than 6 months prior to study. 
 Women of childbearing potential with a positive serum beta hCG. 
 Patient has a history of dementia, psychosis or other disorder 
affecting their mental status to the point where they cannot consent 
or comply with study guidelines. 
 BMI < 21 
 Weight < 100lbs 
 Unintentional weight loss ≥10% in the last 3 mos 
 Prior invasive non-breast malignancy (except non-melanomatous 
skin cancer, carcinoma in situ of the cervix) unless disease free for 
a minimum of 2 years prior to registration 

 
 
 
 
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 Two or more breast cancers not resectable through a single 
lumpectomy incision 
 Non-epithelial breast malignancies such as sarcoma or lymphoma 
 Prior radiotherapy to the ipsilateral breast or prior radiation to the 
region of the breast that would result in overlap of radiation therapy 
fields 
 Severe, active co-morbidity, defined as follows: 
o Unstable angina and/or congestive heart failure requiring 
hospitalization within the last 6 months 
o Transmural myocardial infarction within the last 6 months 
o Acute bacterial or fungal infection requiring intravenous 
antibiotics at the time of registration; 
o Chronic Obstructive Pulmonary Disease exacerbation or 
other respiratory illness requiring hospitalization or 
precluding study therapy within 30 days before registration; 
o Hepatic insufficiency resulting in clinical jaundice and/or 
coagulation defects; note, however,that laboratory tests for 
liver function and coagulation parameters are not required for 
entry into this protocol 
o Acquired Immune Deficiency Syndrome (AIDS) or HIV 
positive based upon current CDC definition; note,however, 
that HIV testing is not required for entry into this protocol. 
The need to exclude patients with AIDS or HIV from this 
protocol is necessary because anti-retrivirals may alter 
patient metabolism. 
 Active systemic lupus erythematosus, or any history of scleroderma, 
dermatomyositis with active rash 
Active Gastrointestinal/Malabsorption disorder at the discretion of 
the Principal Investigator 
o  Inflammatory Bowel Disease 
o Celiac Disease 
o  Chronic Pancreatitis 
o Chronic Diarrhea or Vomiting 
o Active Eating Disorder 
 Current use of steroids 
 Active drug/alcohol dependence or abuse history.   
 Decisionally impaired patients. 
 
 
 
 
 
 
 
 

 
 
 
 
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Appendix XI. PROMIS Cancer Fatigue Short FormREF and FACT-B 
Assessment 
 

 
 
 
 
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