Fasting Mimicking Diet Program to ImpRovE ChemoTherapy in Hormone Receptor Postive (HR+), HER2- Breast Cancer

NCT05503108 | Suspended Phase 3 DMC

• 3 other identifiers: NL80749.058.22 DIRECT 2P22.028BOOG 2022-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 7

Brief Summary

In preclinical research, short-term fasting (STF) protects tumor-bearing mice against the toxic effects of chemotherapy, improves the CD8+ effector T-cell intratumor infiltration, while enhancing the chemotherapy efficacy. Short-term use of a "fasting-mimicking diet" (FMD) caused a major increase in the efficacy of cancer treatment in mice comparable to STF. In humans, the investigators recently performed a multicenter randomized phase II trial showing that patients with Human Epidermal growth factor Receptor 2 (HER2) negative breast cancer treated with neoadjuvant chemotherapy and FMD displayed a better radiological response and a better pathological response (90-100% vs \<90% tumor cell reduction) than patients treated with chemotherapy without FMD (de Groot, Nat Commun 2020; NCT02126449). Therefore these findings will be validated in a phase 3 trial with the underlying hypothesis that FMD during neoadjuvant chemotherapy for breast cancer improves clinical outcomes, potentially due to improved local immunity.

Conditions

Fasting Mimicking Diet; HER2-negative Breast Cancer; Hormone Receptor-positive Breast Cancer; Pathological Complete Response; Objective Response Rate; Neoadjuvant Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Pathological response rate (pCR). Both percentage of pCR and 90-100% tumor loss according to Miller & Payne

  4.5 years

• Objective response rate assessed by MRI (RECIST1.1) after 4 ddAC cycles and at the end of chemotherapy

  4.5 years

Secondary Outcomes (5)

• Determine the effect of treatment on the 3 and 5 year Event-free survival (EFS) and Overall survival (OS)

  7.5 and 9.5 years

• Adverse events ≥grade 3 (maximum of total) difference between treatment arms during neoadjuvant chemotherapy (ddAC, paclitaxel and total).

  4.5 years

• Quality of Life assessed by online questionnaires (EORTC QLQ-C30, EORTC QLQ-BR23), burden of therapy (Distress Thermometer) and Illness Perceptions (B-IPQ)

  5 years

• Cognition assessed by Amsterdam Cognition Scan (ACS) online battery consisting of 7 online neuropsychological tests

  5 years

• Determine the effect of FMD on local immunomodulation and tumor immunity

  6 years

Other Outcomes (2)

• Biomarker analysis to predict treatment outcome

  6 years

• Optional Bioelectrical Impedance Analysis (BIA) for participants at the Leiden University Medical Center (LUMC) to investigate the change in body composition in both treatment arms.

  4.5 years

Study Arms (2)

Fasting Mimicking Diet group

EXPERIMENTAL

Fasting Mimicking Diet 3 days before and the day of neoadjuvant chemotherapy (ddAC, T)

Other: Fasting Mimicking diet program

Normal Diet group

NO INTERVENTION

Standard neoadjuvant chemotherapy (ddAC, T)

Interventions

Fasting Mimicking diet program OTHER

Fasting mimicking diet by L-Nutra, a 4-day low caloric, low protein, vegetarian diet 3 days prior to and the day of neoadjuvant chemotherapy administration. The FMD will take place every 4 weeks, thus in total 5 times (2x during ddAC, 3x during Paclitaxel) during the neoadjuvant chemotherapy.

Also known as: Xentigen™

Fasting Mimicking Diet group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical stage II-III (cT1cN+ or ≥T2 any cN, cM0), HR+, HER2- breast cancer
• Detectable and measurable disease (breast and/or lymph nodes)
• World Health Organization (WHO) performance status 0-2
• Adequate organ function assessed by standard pre-treatment assessment:
• Adequate bone marrow function: white blood cells (WBCs) ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
• Adequate liver function: bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
• Adequate renal function: the calculated creatinine clearance should be ≥50 mL/min
• Available for treatment and follow-up
• Written informed-consent
• Willing to fill in Quality Of Life and Cognition questionnaires
• Ability to read and understand Dutch language, accessibility to a computer with internet connection and independent use of computer

You may not qualify if:

• Patient history of invasive or ipsilateral non-invasive breast cancer
• Body mass index (BMI) \< 18.5 kg/m2
• Pregnancy or lactating
• Food allergy for ingredients of FMD (nuts, soy, honey)
• A metabolic condition affecting gluconeogenesis or adaptation to periodic fasting. (Diabetes Mellitus for example)

Sponsors & Collaborators

• Leiden University Medical Center: lead
• The Netherlands Cancer Institute: collaborator
• Borstkanker Onderzoek Groep: collaborator
• Comprehensive Cancer Centre The Netherlands: collaborator
• Koningin Wilhelmina Fonds: collaborator
• World Cancer Research Fund International: collaborator
• L-Nutra Inc: collaborator

Study Sites (7)

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

Location

Rode Kruis ziekenhuis

Beverwijk, 1942 LE, Netherlands

Location

Alexander Monro Ziekenhuis

Bilthoven, Netherlands

Location

Reinier de Graaf ziekenhuis

Delft, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Related Publications (4)

• de Groot S, Lugtenberg RT, Cohen D, Welters MJP, Ehsan I, Vreeswijk MPG, Smit VTHBM, de Graaf H, Heijns JB, Portielje JEA, van de Wouw AJ, Imholz ALT, Kessels LW, Vrijaldenhoven S, Baars A, Kranenbarg EM, Carpentier MD, Putter H, van der Hoeven JJM, Nortier JWR, Longo VD, Pijl H, Kroep JR; Dutch Breast Cancer Research Group (BOOG). Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nat Commun. 2020 Jun 23;11(1):3083. doi: 10.1038/s41467-020-16138-3.

  PMID: 32576828 BACKGROUND

• Lugtenberg RT, de Groot S, Kaptein AA, Fischer MJ, Kranenbarg EM, Carpentier MD, Cohen D, de Graaf H, Heijns JB, Portielje JEA, van de Wouw AJ, Imholz ALT, Kessels LW, Vrijaldenhoven S, Baars A, Fiocco M, van der Hoeven JJM, Gelderblom H, Longo VD, Pijl H, Kroep JR; Dutch Breast Cancer Research Group (BOOG). Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial. Breast Cancer Res Treat. 2021 Feb;185(3):741-758. doi: 10.1007/s10549-020-05991-x. Epub 2020 Nov 11.

  PMID: 33179154 BACKGROUND

• de Groot S, Pijl H, van der Hoeven JJM, Kroep JR. Effects of short-term fasting on cancer treatment. J Exp Clin Cancer Res. 2019 May 22;38(1):209. doi: 10.1186/s13046-019-1189-9.

  PMID: 31113478 BACKGROUND

• 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: 27411588 BACKGROUND

Related Links

• Related Info

Study Officials

• Judith R Kroep, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Drs J.R. Kroep

Study Record Dates

• First Submitted: July 24, 2022
• First Posted: August 16, 2022
• Study Start: March 17, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (7)