Can Fasting Decrease the Side Effects of Chemotherapy?

Chemotherapy Effect Clinical Trial

Official title:

Can Fasting Decrease the Side Effects of Chemotherapy?

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04027478
• Other study ID #: SIMR_Onc18_IIS_D'Andre_Fasting
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 1, 2019
• Est. completion date: February 1, 2021

Study information

• Verified date: July 2019
• Source: Sutter Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective randomized crossover trial. Patients will be randomized to the FMD or regular diet during three rounds of chemotherapy. After the third round, patients will cross over to the opposite arm. The primary hypothesis is that there will be fewer cases of Grade 2-4 nausea when patients are in the FMD sequence. The primary objective is to assess differences in toxicities in patients undergoing chemotherapy with a combination of taxol/carboplatin when using a fasting mimicking diet when compared to normal diet before and after treatment.

Description:

Randomization and blinding:

Subjects will be allocated to sequence 1 (normal diet first, FMD second) or sequence 2 (FMD first, normal diet second) using a computer generated randomization scheme. There will be no blinding

Intervention:

Over the course of three rounds of chemotherapy, patients in the FMD will consume a diet that consists of 10 cal/kg/day and includes 50% fat, 40% carbohydrates, and no more than 10% protein. The diet includes nuts, olives, vegetable broth, broccoli/cauliflower, white rice/puffed rice cake, onion, tea/coffee, almond milk. The diet prohibits meat products, dairy, alcohol, sugar, and artificial sweeteners. Patients will be instructed to drink 2 cups of water each morning, take their usual medications and limit exercise to walking.

The table below provides the schedule of fasting during the cycle of chemotherapy

(Time during chemotherapy cycle, Diet)

• 2 days prior to chemotherapy, Fasting mimicking diet

• 1 day prior to chemotherapy, Fasting mimicking diet

• Day of chemotherapy, Full fasting(water only)

• 1 day after chemotherapy, Fasting mimicking diet

• 2 days after chemotherapy, Fasting mimicking diet

Prior to each chemotherapy cycle and coincident FMD arm, weight, and laboratory testing will be conducted and patients will be asked to keep track of side effects as per usual care for patients undergoing chemotherapy. Patients will be asked to keep a food log and record the quality of their sleep as part of the study.

There will be no restrictions for use of usual standard medications, including anti-nausea medication. This is generally Zofran oral, q8 hours PRN. Anti-nausea medication usage will be recorded in the study database. Although it is expected to be consistent throughout the diet and control periods for each subject, dosage and frequency will be recorded throughout the study, and it will be noted if anti-nausea medication is effective during the control period for each subject.

Endpoint evaluation:

Severity of AEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 for toxicity and adverse event reporting. A copy of the CTCAE Version 3.0 can be downloaded from https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf.

AEs not corresponding to the CTCAE term will be assessed according to their impact on the subject's ability to perform daily activities as follows:

Mild (grade 1) - the AE does not interfere in a significant manner with the subject's normal functioning level. It may be an annoyance.

• Moderate (grade 2) - the AE produces some impairment of functioning, but is not hazardous to health. It is uncomfortable or an embarrassment.

• Severe (grade 3) - the AE produces significant impairment of functioning or incapacitation and is a definite hazard to the subject's health.

• Life threatening (grade 4) - Life threatening or disabling.

• Fatal (grade 5) Causes death of the participant.

Estimated study duration:

Patient participation is approximately 16 weeks.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 39
• Est. completion date: February 1, 2021
• Est. primary completion date: August 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years of age and older

• English speaking

• Patients undergoing chemotherapy with Taxol/carboplatin planned for at least 6 cycles

• Willing to comply with diet and tests

• No significant medical problem that would make fasting dangerous (insulin dependent diabetes, history of hypoglycemia)

Exclusion Criteria:

• Insulin dependent diabetes

• Pregnancy

• History of hypoglycemia, or any other medical condition that the treating physician considers not suitable for fasting

Related Conditions & MeSH terms

• Chemotherapeutic Toxicity
• Chemotherapy Effect
• Fasting

Intervention

Dietary Supplement:
• FMD
fasting mimicking diet

Locations

Country	Name	City	State
United States	Sutter Cancer Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Sutter Health

Country where clinical trial is conducted

United States, 

References & Publications (10)

Brandhorst S, Longo VD. Fasting and Caloric Restriction in Cancer Prevention and Treatment. Recent Results Cancer Res. 2016;207:241-66. doi: 10.1007/978-3-319-42118-6_12. Review. — View Citation

de Groot S, Vreeswijk MP, Welters MJ, Gravesteijn G, Boei JJ, Jochems A, Houtsma D, Putter H, van der Hoeven JJ, Nortier JW, Pijl H, Kroep JR. The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. BMC Cancer. 2015 Oct 5;15:652. doi: 10.1186/s12885-015-1663-5. — View Citation

Di Biase S, Longo VD. Fasting-induced differential stress sensitization in cancer treatment. Mol Cell Oncol. 2015 Dec 10;3(3):e1117701. doi: 10.1080/23723556.2015.1117701. eCollection 2016 May. — View Citation

Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, Pistoia V, Wei M, Hwang S, Merlino A, Emionite L, de Cabo R, Longo VD. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012 Mar 7;4(124):124ra27. doi: 10.1126/scitranslmed.3003293. Epub 2012 Feb 8. — View Citation

Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK, Wei M, Cohen P, Crimmins EM, Longo VD. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014 Mar 4;19(3):407-17. doi: 10.1016/j.cmet.2014.02.006. — View Citation

Mendelsohn AR, Larrick JW. Prolonged fasting/refeeding promotes hematopoietic stem cell regeneration and rejuvenation. Rejuvenation Res. 2014 Aug;17(4):385-9. doi: 10.1089/rej.2014.1595. — View Citation

Raffaghello L, Safdie F, Bianchi G, Dorff T, Fontana L, Longo VD. Fasting and differential chemotherapy protection in patients. Cell Cycle. 2010 Nov 15;9(22):4474-6. Epub 2010 Nov 15. — View Citation

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. — View Citation

Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. — View Citation

Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017 Feb 15;9(377). pii: eaai8700. doi: 10.1126/scitranslmed.aai8700. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nausea Grade	Grade 2-4 nausea when patients are in the FMD sequence versus the non-fasting sequence	16 weeks
Secondary	FMD Tolerability as measured by adverse events	Severity of AEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 for toxicity and adverse event reporting. AEs not corresponding to the CTCAE term will be assessed according to their impact on the subject's ability to perform daily activities as follows: Mild (grade 1) - the AE does not interfere in a significant manner with the subject's normal functioning level. It may be an annoyance.; Moderate (grade 2) - the AE produces some impairment of functioning, but is not hazardous to health. It is uncomfortable or an embarrassment.; Severe (grade 3) - the AE produces significant impairment of functioning or incapacitation and is a definite hazard to the subject's health.; Life threatening (grade 4) - Life threatening or disabling.; Fatal (grade 5) - Causes death of the participant.	16 weeks
Secondary	FMD Tolerability as measured by QOL Questionnaire	Mean differences in QOL between patients during the FMD versus normal diet sequence will be measured using a repeated measures analysis of variance. QOL questionnaire used will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.	16 weeks
Secondary	Incidence of neutropenia	Differences in neutropenia between patients during the FMD versus normal diet sequence	16 weeks

External Links

•   Dhand NK, Khatkar MS. Statulator: An online statistical calculator. Sample Size Calculator for Comparing Two Paired Proportions. 2014;Accessed 30 March 2018