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

• ClinicalTrials.gov Identifier: NCT01819233
• Recruitment Status: Completed
• First Posted: March 27, 2013
• Results First Posted: December 23, 2019
• Last Update Posted: December 23, 2019
• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Information provided by (Responsible Party): Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• 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
• Interventions: Behavioral: Behavioral dietary intervention; Procedure: Therapeutic conventional surgery; Radiation: Radiation therapy; Other: Counseling intervention; Procedure: Quality-of-life assessment
• Enrollment: 38

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Period Title: Overall Study
Started	38
Completed	32
Not Completed	6

Baseline Characteristics

Arm/Group Title		Behavioral Dietary Intervention
Arm/Group Description		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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Baseline Participants		38
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	38 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	33 86.8%
	>=65 years	5 13.2%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	38 participants
	Female	38 100.0%
	Male	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	38 participants
	Hispanic or Latino	4 10.5%
	Not Hispanic or Latino	33 86.8%
	Unknown or Not Reported	1 2.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	38 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 2.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	15 39.5%
	White	18 47.4%
	More than one race	0 0.0%
	Unknown or Not Reported	4 10.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	38 participants
		38

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Are Adherent to the Diet Restriction
Description	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%.
Time Frame	Up to week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	32
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants
	28 [1]; (NA to 74.5)

[1]

one sided lower confidence limit as one-sided alpha used.

2. Secondary Outcome

Title	Change in Body Fat Measurement
Description	Analyzed via a paired t-test. Change in body fat measurement as determined by the Durnin-Womersley 4-fold technique
Time Frame	Baseline to 4 weeks after completion of study

Outcome Measure Data

Analysis Population Description

patients who did not complete all assessments were not included in the analysis

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	29
Mean (95% Confidence Interval); Unit of Measure: percentage of change in body fat
	-3.1; (-4.7 to -1.5)

3. Secondary Outcome

Title	Change in Body Mass Index (BMI)
Description	Assessed via mixed-effects regression. Weight changes over time assessed by modeling BMI as a function of time
Time Frame	Baseline to 4 weeks after completion of study

Outcome Measure Data

Analysis Population Description

participants who did not complete all timepoint measurements were not included.

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	31
Mean (95% Confidence Interval); Unit of Measure: percentage of change in BMI
	-1.2; (-1.6 to -0.8)

4. Secondary Outcome

Title	Change in Heart Rate Over Time
Description	Assessed via mixed-effects regression.
Time Frame	Baseline to 4 weeks after completion of study

Outcome Measure Data

Analysis Population Description

only participants who completed all timepoints were included

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	32
Mean (Standard Error); Unit of Measure: beats per minute
	67.3 (1.5)

5. Secondary Outcome

Title	Patterns of Change Over Time in Serum Markers
Description	Assessed via mixed-effects regression.
Time Frame	Baseline to 4 weeks after completion of study

Outcome Measure Data Not Reported

6. Secondary Outcome

Title	Patterns of Change Over Time in Psycho-social Outcomes Measured Using the Functional Assessment of Cancer Therapy-Breast (FACT-B)
Description	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)
Time Frame	Baseline to 4 weeks after completion of study

Outcome Measure Data

Analysis Population Description

patients who did not complete all questionnaire timepoints were not included in the analysis

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	31
Mean (95% Confidence Interval); Unit of Measure: score on a scale
	0.8; (-6.2 to 7.8)

7. Secondary Outcome

Title	Local Recurrence
Description	Analyzed via survival methods, specifically the Kaplan-Meier method and the logrank test.
Time Frame	Up to 4 weeks after completion of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	38
Measure Type: Count of Participants; Unit of Measure: Participants
	NA [1]

[1]

Sincere efforts were made to gather and report the data, however, no data is available for this endpoint.

8. Secondary Outcome

Title	Distant Metastases
Description	Analyzed via survival methods, specifically the Kaplan-Meier method and the logrank test.
Time Frame	Up to 4 weeks after completion of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	38
Measure Type: Count of Participants; Unit of Measure: Participants
	NA [1]

[1]

Sincere efforts were made to gather and report the data, however, no data is available for this endpoint.

9. Secondary Outcome

Title	Progression Free Survival
Description	Analyzed via survival methods, specifically the Kaplan-Meier method and the logrank test.
Time Frame	Up to 4 weeks after completion of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	38
Measure Type: Count of Participants; Unit of Measure: Participants
	NA [1]

[1]

Sincere efforts were made to gather and report the data, however, no data is available for this endpoint.

10. Secondary Outcome

Title	Overall Survival
Description	Analyzed via survival methods, specifically the Kaplan-Meier method and the logrank test.
Time Frame	Up to 4 weeks after completion of study

Outcome Measure Data

Analysis Population Description

Insufficient data was collected to conduct survival analysis as there were participants who were lost to follow up.

Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description:	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
Overall Number of Participants Analyzed	38
Measure Type: Count of Participants; Unit of Measure: Participants
	NA [1]

[1]

Sincere efforts were made to gather and report the data, however, no data is available for this endpoint.

Adverse Events

Time Frame	baseline through 5 weeks after completion of study diet.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Behavioral Dietary Intervention
Arm/Group Description	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. Behavioral dietary intervention: Receive caloric restricted dietary intervention Therapeutic conventional surgery: Undergo definitive lumpectomy Radiation therapy: Undergo radiation therapy Counseling intervention: Receive dietary counseling Quality-of-life assessment: Ancillary studies
All-Cause Mortality
	Behavioral Dietary Intervention
	Affected / at Risk (%)
Total	0/38 (0.00%)
Serious Adverse Events
	Behavioral Dietary Intervention
	Affected / at Risk (%)	# Events
Total	0/38 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Behavioral Dietary Intervention
	Affected / at Risk (%)	# Events
Total	14/38 (36.84%)
General disorders
fatigue *	13/38 (34.21%)	38
hot flashes *	5/38 (13.16%)
Skin and subcutaneous tissue disorders
Dermatitis *	13/38 (34.21%)	38
hyperpigmentation *	10/38 (26.32%)
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Nicole Simone
• Organization: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Phone: 215-955-6702
• EMail: nicole.simone@jefferson.edu

Publications:

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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.

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.

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.

• Responsible Party: Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
• ClinicalTrials.gov Identifier: NCT01819233
• Other Study ID Numbers: 12G.616; 2012-94 ( Other Identifier: CCRRC )
• First Submitted: March 22, 2013
• First Posted: March 27, 2013
• Results First Submitted: October 29, 2019
• Results First Posted: December 23, 2019
• Last Update Posted: December 23, 2019