NCT03340935

Brief Summary

In preclinical studies, cyclic calorie-restricted diets reduce the risk of several cancers and improve the antitumor activity of standard treatments against already established malignancies.In particular, the fasting mimicking diet (FMD), a plant-based, calorie-restricted, low carbohydrate, low-protein diet to be repeated cyclically every 3-4 weeks, enhances the antitumor activity of cytotoxic chemotherapy, while contemporarily protecting healthy tissues and stimulating antitumor immunity. Most of these effects are likely mediated by the reduction of blood glycemia and growth factors, such as insulin and insulin-like growth factor 1 (IGF-1). When administered to healthy volunteers, cyclic FMD has been shown to be safe and capable of reducing risk factors for different chronic diseases. However, the effects of the FMD in cancer patient populations have not been evaluated so far. This study aims to assess the safety, feasibility and metabolic effects of the FMD in cancer patients treated with different standard antitumor therapies. Patients with any malignancy, with the exception of small cell neuroendocrine tumors, will be considered for enrollment in this study. The FMD will be administered up to a maximum of 8 consecutive cycles in combination with standard adjuvant treatments or therapies for advanced disease.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
101

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Feb 2017

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2017

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

November 5, 2017

Completed
9 days until next milestone

First Posted

Study publicly available on registry

November 14, 2017

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 30, 2020

Completed
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2020

Completed
Last Updated

August 4, 2020

Status Verified

August 1, 2020

Enrollment Period

3.5 years

First QC Date

November 5, 2017

Last Update Submit

August 2, 2020

Conditions

Malignant NeoplasmCancer

Keywords

fasting mimicking dietmalignant neoplasmmetabolismmetabolic effectsadjuvant treatmentmetastatic setting

Outcome Measures

Primary Outcomes (1)

  • Safety of the fasting mimicking diet (FMD) in cancer patients

    Safety is assessed by recording each adverse (AE) occurring during the period on diet. All AEs will be graded according to the NCI CTCAE v 4.03. Serious adverse events (SAEs) will be also reported.

    2 years

Secondary Outcomes (7)

  • Feasibility of the FMD in cancer patients

    16 months

  • Metabolic effects of the FMD

    16 months

  • Effects of the FMD on blood growth factors

    16 months

  • Weight changes during the FMD

    16 months

  • Changes in blood cell counts

    16 months

  • +2 more secondary outcomes

Study Arms (1)

Fasting mimicking diet

EXPERIMENTAL

Fasting mimicking diet (FMD)

Other: Fasting mimicking diet

Interventions

Fasting mimicking dietOTHER

Fasting Mimicking Diet (or FMD) consists in a 5-day plant-based, low-calorie (600 Kcal on day 1, followed by 300 KCal/day on days 2 to 5), low-protein, low carbohydrate diet

Fasting mimicking diet

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Cytologically or Histologically confirmed diagnosis of malignant neoplasm
  • Capability of swallowing plant-based foods foreseen by the FMD
  • Body mass index (BMI) ≥ 20 kg/m2
  • Adequate bone marrow function, including:
  • Hemoglobin \> 9 g/dl
  • Piatelets \> 75,000/µl
  • Absolute neutrophil count (ANC) \> 1,500/µl
  • Creatinine \< 1.5 mg/dl or calculated creatinine clearance ≥50 mL/min
  • Uric acid \< 6 mg/dl
  • Fasting glucose \> 65 mg/dl
  • Total bilirubin \< 2 mg/dl or \< ULN, except for patients with Gilbert syndrome
  • Written informed consent according to the local Ethics Committee requirements
  • Willing and ability to accomplish blood and urinary examinations according to the protocol
  • Ability to maintain a daily contact (by phone or email) with the study staff for the communication of crucial clinical information, including daily body weight, blood pressure, health status and adverse events during each of the 5 days on diet

You may not qualify if:

  • Small cell neuroendocrine carcinoma
  • Unintentional weight loss ≥ 5% in the last 3-6 months
  • Known HIV infection
  • Pregnancy or lactation
  • History of alcohol abuse
  • Diagnosis of diabetes mellitus type I or type II that requires medical treatment
  • Fasting glucose \> 200 mg/dl
  • Clinically meaningful cardiovascular, renal or pulmonary diseases
  • Current treatment with antipsychotics

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Related Publications (9)

  • Vernieri C, Casola S, Foiani M, Pietrantonio F, de Braud F, Longo V. Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions. Cancer Discov. 2016 Dec;6(12):1315-1333. doi: 10.1158/2159-8290.CD-16-0615. Epub 2016 Nov 21.

    PMID: 27872127BACKGROUND

  • Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 18.

    PMID: 26094889RESULT

  • 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.

    PMID: 26438237RESULT

  • Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, Cacciottolo M, Martin-Montalvo A, de Cabo R, Wei M, Morgan TE, Longo VD. Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. Cancer Cell. 2016 Jul 11;30(1):136-146. doi: 10.1016/j.ccell.2016.06.005.

    PMID: 27411588RESULT

  • Dorff TB, Groshen S, Garcia A, Shah M, Tsao-Wei D, Pham H, Cheng CW, Brandhorst S, Cohen P, Wei M, Longo V, Quinn DI. Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer. 2016 Jun 10;16:360. doi: 10.1186/s12885-016-2370-6.

    PMID: 27282289RESULT

  • 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.

    PMID: 22323820RESULT

  • Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, Cohen P, Longo VD. Fasting and cancer treatment in humans: A case series report. Aging (Albany NY). 2009 Dec 31;1(12):988-1007. doi: 10.18632/aging.100114.

    PMID: 20157582RESULT

  • Ligorio F, Lobefaro R, Fuca G, Provenzano L, Zanenga L, Nasca V, Sposetti C, Salvadori G, Ficchi A, Franza A, Martinetti A, Sottotetti E, Formisano B, Depretto C, Scaperrotta G, Belfiore A, Vingiani A, Ferraris C, Pruneri G, de Braud F, Vernieri C. Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial. Int J Cancer. 2024 Jan 1;154(1):114-123. doi: 10.1002/ijc.34701. Epub 2023 Aug 24.

    PMID: 37615485DERIVED

  • Ligorio F, Fuca G, Provenzano L, Lobefaro R, Zanenga L, Vingiani A, Belfiore A, Lorenzoni A, Alessi A, Pruneri G, de Braud F, Vernieri C. Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial. Eur J Cancer. 2022 Sep;172:300-310. doi: 10.1016/j.ejca.2022.05.046. Epub 2022 Jul 8.

    PMID: 35810555DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

  • Filippo de Braud, M.D.

    SC Oncologia Medica 1, Fondazione IRCCS Istituto Nazionale dei Tumori

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Dean of Medical Oncology and Hematology Department

Study Record Dates

First Submitted

November 5, 2017

First Posted

November 14, 2017

Study Start

February 1, 2017

Primary Completion

July 30, 2020

Study Completion

July 31, 2020

Last Updated

August 4, 2020

Record last verified: 2020-08

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)