Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy (CAREFOR)

A Feasibility Pilot Trial Evaluating Caloric Restriction for Oncology Research in Early Stage Breast Cancer Patients

This pilot clinical trial studies caloric restriction in patients with stage 0-I breast cancer during surgery and radiation therapy. Reducing caloric intake may prevent disease progression in patients with breast cancer. Radiation therapy uses high energy x rays to kill tumor cells. Giving dietary intervention and radiation therapy together may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Stage IA Breast Cancer; Stage IB Breast Cancer; Recurrent Breast Cancer; Ductal Breast Carcinoma in Situ; Invasive Lobular Breast Carcinoma; Lobular Breast Carcinoma in Situ; Invasive Ductal Breast Carcinoma
• Intervention / Treatment: Procedure: Quality-of-life assessment; Radiation: Radiation therapy; Behavioral: Behavioral dietary intervention; Procedure: Therapeutic conventional surgery; Other: Counseling intervention

Detailed Description

PRIMARY OBJECTIVE:

1. Investigate the feasibility of a clinical trial administering ionizing radiation with concurrent caloric restriction (CR) for the treatment of breast cancer.

   SECONDARY OBJECTIVE:

2. Investigate measurable changes of patient characteristics and tissue and serum from CR conditions to determine a metric for evaluating this treatment in future studies.

OUTLINE:

Beginning 2-4 weeks after completion of lumpectomy, patients receive food diaries to complete for 7-10 days. Dietary counselors then give patients guidelines for dietary modifications to reduce caloric intake by 25% of their normal diet. Patients follow caloric restricted diet for 10 weeks (2 weeks prior to radiation therapy, during 6 weeks of radiation therapy, and at least 2 weeks after radiation therapy). Patients undergo radiation therapy once daily (QD) 5 days a week for 6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pathologically proven diagnosis of ductal carcinoma in situ (DCIS) or invasive breast cancer
2. Ability to have breast conservation as determined by the judgment of the radiation oncologist, for which the radiation oncologist has determined that he or she will only treat the whole breast and not regional lymph nodes
3. The patient must be female
4. Age >= 18
5. If multifocal breast cancer, then it must be able to be resected through a single lumpectomy incision

6. Appropriate stage for protocol entry, including no clinical evidence for distant metastases, based upon the following minimum diagnostic workup:

   1. History/physical examination, including breast exam and documentation of weight and Karnofsky performance status of 80-100% for at least 60 days prior to study entry
   2. Ipsilateral mammogram within 6 months prior to study entry
7. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry
8. Women of childbearing potential must be non-pregnant and non-lactating and willing to use medically acceptable form of contraception during radiation therapy
9. Patient must capable of and provide study specific informed consent prior to study entry
10. Body mass index (BMI) >= 21
11. Weight >= 100 lbs
12. No prior history of non-breast malignancies in the past 2 years unless it was a non-melanomatous skin lesion or carcinoma in situ of the cervix

13. Patient must not have any of the following severe, active co-morbidity, defined as follows:

    1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    2. Transmural myocardial infarction within the last 6 months
    3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
    5. 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
    6. Acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) positive based upon current Centers for Disease and Control (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-retrovirals may alter patient metabolism
14. Patient must not have active systemic lupus, erythematosus, or any history of scleroderma, dermatomyositis with active rash
15. 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

16. Patient may not have any active gastrointestinal/malabsorption disorder at the discretion of the Principal Investigator

    1. Inflammatory bowel disease
    2. Celiac disease
    3. Chronic pancreatitis
    4. Chronic diarrhea or vomiting
    5. Active eating disorder
17. Creatinine < 1.7
18. Not currently taking steroids
19. No currently active pituitary secreting tumors up to physician discretion
20. No history of or current active drug/alcohol dependence
21. No patients being decisionally impaired

Exclusion Criteria:

1. Patient is not a candidate for breast conservation
2. Patient is male
3. Age < 18 years
4. Patient requires regional lymph node irradiation therapy
5. Patient has evidence of distant metastases
6. Karnofsky performance status less than 80% within 60 days prior to study
7. Ipsilateral mammogram done greater than 6 months prior to study
8. Women of childbearing potential with a positive serum beta human chorionic gonadotropin (hCG)
9. 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
10. BMI < 21
11. Weight < 100 lbs
12. Weight loss >= 10% in the last 3 months (mos)
13. 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
14. Two or more breast cancers not resectable through a single lumpectomy incision
15. Non-epithelial breast malignancies such as sarcoma or lymphoma
16. Prior radiotherapy to the ipsilateral breast or prior radiation to the region of the breast that would result in overlap of radiation therapy fields

17. Severe, active co-morbidity, defined as follows:

    1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    2. Transmural myocardial infarction within the last 6 months
    3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
    5. 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
    6. 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-retrovirals may alter patient metabolism
18. Active systemic lupus, erythematosus, or any history of scleroderma, dermatomyositis with active rash

19. Active gastrointestinal/malabsorption disorder at the discretion of the Principal Investigator

    1. Inflammatory bowel disease
    2. Celiac disease
    3. Chronic pancreatitis
    4. Chronic diarrhea or vomiting
    5. Active eating disorder
20. Creatinine >= 1.7
21. Current use of steroids
22. Pituitary secreting tumors up to physician discretion
23. Active drug/alcohol dependence or abuse history
24. Decisionally impaired patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Behavioral dietary intervention; Beginning 2-4 weeks after completion of lumpectomy, patients receive food diaries to complete for 7-10 days. Dietary counselors then give patients guidelines for dietary modifications to reduce caloric intake by 25% of their normal diet. Patients follow caloric restricted diet for 10 weeks (2 weeks prior to radiation therapy, during 6 weeks of radiation therapy, and at least 2 weeks after radiation therapy). Patients undergo radiation therapy QD 5 days a week for 6 weeks.

Procedure: Quality-of-life assessment; Ancillary studies; Other Names: Quality of life assessment; Radiation: Radiation therapy; Undergo radiation therapy; Other Names: Irradiation; Radiation; Radiotherapy; Behavioral: Behavioral dietary intervention; Receive caloric restricted dietary intervention; Procedure: Therapeutic conventional surgery; Undergo definitive lumpectomy; Other: Counseling intervention; Receive dietary counseling; Other Names: Counseling and communications studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Are Adherent to the Diet Restriction	Computed along with a 95% exact confidence interval. Exact binomial test (with a one-sided alpha of 0.05) will be used to test whether adherence is greater than 60%.	Up to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Fat Measurement	Analyzed via a paired t-test. Change in body fat measurement as determined by the Durnin-Womersley 4-fold technique	Baseline to 4 weeks after completion of study
Change in Body Mass Index (BMI)	Assessed via mixed-effects regression. Weight changes over time assessed by modeling BMI as a function of time	Baseline to 4 weeks after completion of study
Change in Heart Rate Over Time	Assessed via mixed-effects regression.	Baseline to 4 weeks after completion of study
Patterns of Change Over Time in Serum Markers	Assessed via mixed-effects regression.	Baseline to 4 weeks after completion of study
Patterns of Change Over Time in Psycho-social Outcomes Measured Using the Functional Assessment of Cancer Therapy-Breast (FACT-B)	Assessed via mixed-effects regression. The FACT-B is a questionnaire using a 5-point Likert scale (0-Not at all to 4-Very much)	Baseline to 4 weeks after completion of study
Local Recurrence	Analyzed via survival methods, specifically the Kaplan-Meier method and the logrank test.	Up to 4 weeks after completion of study
Distant Metastases	Analyzed via survival methods, specifically the Kaplan-Meier method and the logrank test.	Up to 4 weeks after completion of study
Progression Free Survival	Analyzed via survival methods, specifically the Kaplan-Meier method and the logrank test.	Up to 4 weeks after completion of study
Overall Survival	Analyzed via survival methods, specifically the Kaplan-Meier method and the logrank test.	Up to 4 weeks after completion of study

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Investigators: Principal Investigator: Nicole Simone, MD, Thomas Jefferson University

Publications and helpful links

General Publications

• Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006 Dec 14;444(7121):840-6. doi: 10.1038/nature05482.
• Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella E, Hwang D, Cohen P, Bianchi G, Longo VD. Reduced levels of IGF-I 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. doi: 10.1158/0008-5472.CAN-09-3228. Epub 2010 Feb 9.
• 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. doi: 10.1371/journal.pone.0044603. Epub 2012 Sep 11.
• Longo VD, Fontana L. Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol Sci. 2010 Feb;31(2):89-98. doi: 10.1016/j.tips.2009.11.004. Epub 2010 Jan 25.
• 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;54:131-52. doi: 10.1146/annurev.med.54.101601.152156. Epub 2001 Dec 3.
• Rous P. THE INFLUENCE OF DIET ON TRANSPLANTED AND SPONTANEOUS MOUSE TUMORS. J Exp Med. 1914 Nov 1;20(5):433-51. doi: 10.1084/jem.20.5.433.
• Tannenbaum A. Effects of Varying Caloric Intake Upon Tumor Incidence and Tumor Growth. Annals of the New York Academy of Sciences. 15 Dec 2006 2006;49(1).
• Berrigan D, Perkins SN, Haines DC, Hursting SD. Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis. 2002 May;23(5):817-22. doi: 10.1093/carcin/23.5.817.
• Zhu Z, Jiang W, Thompson HJ. Effect of energy restriction on tissue size regulation during chemically induced mammary carcinogenesis. Carcinogenesis. 1999 Sep;20(9):1721-6. doi: 10.1093/carcin/20.9.1721.
• 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. 1990 May 15;51(1):67-73. doi: 10.1016/0304-3835(90)90232-m.
• 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. 1994 Oct 11;91(21):9995-9. doi: 10.1073/pnas.91.21.9995.
• Turner BC, Haffty BG, Narayanan L, Yuan J, Havre PA, Gumbs AA, Kaplan L, Burgaud JL, Carter D, Baserga R, Glazer PM. Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res. 1997 Aug 1;57(15):3079-83.
• Perer ES, Madan AK, Shurin A, Zakris E, Romeguera K, Pang Y, Beech DJ. Insulin-like growth factor I receptor antagonism augments response to chemoradiation therapy in colon cancer cells. J Surg Res. 2000 Nov;94(1):1-5. doi: 10.1006/jsre.2000.5923.
• Donohoe CL, Doyle SL, Reynolds JV. Visceral adiposity, insulin resistance and cancer risk. Diabetol Metab Syndr. 2011 Jun 22;3:12. doi: 10.1186/1758-5996-3-12.
• National Institutes of Health. http://www.clincaltrials.gov.
• Arguin H, Dionne IJ, Senechal M, Bouchard DR, Carpentier AC, Ardilouze JL, Tremblay A, Leblanc C, Brochu M. 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. 2012 Aug;19(8):870-6. doi: 10.1097/gme.0b013e318250a287.

Helpful Links

• Thomas Jefferson University Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2013
• Primary Completion (Actual): September 14, 2017
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: March 22, 2013
• First Submitted That Met QC Criteria: March 22, 2013
• First Posted (Estimated): March 27, 2013

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma, Ductal; Carcinoma in Situ; Breast Neoplasms; Carcinoma; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Carcinoma, Ductal, Breast
• Other Study ID Numbers: 12G.616; 2012-94 (Other Identifier: CCRRC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No