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Fasting Mimicking DietPhase 3DIRECT-2NCT05503108

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

A Phase 3 study testing Fasting Mimicking diet program in people with Fasting Mimicking Diet and HER2-negative Breast Cancer, run by Leiden University Medical Center at 7 sites in Netherlands.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fasting Mimicking diet program
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
7 sitesNetherlands
Study dates
17 Mar 2023to 1 Jan 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • Patient history of invasive or ipsilateral non-invasive breast cancer
  • Active malignancy in the last 5 years, with the exclusion of basal cell carcinoma or pre-invasive cervical neoplasia/dysplasia.
  • 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)

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Netherlands7 sites

  • Noordwest Ziekenhuisgroep

    Alkmaar

  • Rode Kruis ziekenhuis

    Beverwijk, 1942 LE

  • Alexander Monro Ziekenhuis

    Bilthoven

  • Reinier de Graaf ziekenhuis

    Delft

  • Deventer Ziekenhuis

    Deventer

  • Ziekenhuis Gelderse Vallei

    Ede

  • Leiden University Medical Center

    Leiden

Other trials in Netherlands

About this study

Official title: DIRECT-2: Fasting Mimicking Diet Program to ImpRovE ChemoTherapy in HR+, HER2- Breast Cancer

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.

Read the detailed description

STF during neadjuvant chemotherapy aiming to improve the chemotherapy efficacy and decline the side effects in patients with stage II-III HR+, HER2- breast cancer

Being tested
Fasting Mimicking diet program

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fasting Mimicking diet programOther

    Also called Xentigen™

    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.

Study groups in NCT05503108
Study groupRoleWhat they receive
Fasting Mimicking Diet groupExperimentalFasting Mimicking Diet 3 days before and the day of neoadjuvant chemotherapy (ddAC, T)
Receives: Other: Fasting Mimicking diet program
Normal Diet groupNo interventionStandard neoadjuvant chemotherapy (ddAC, T)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 4.5 years

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

    Measured: 4.5 years

Secondary outcomes (5)

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

    Measured: 7.5 and 9.5 years

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

    Measured: 4.5 years

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

    Validated online questionnaires take place at baseline, after 4 ddAC cycles, before surgery and 6 months after surgery.

    Measured: 5 years

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

    online questionnaires take place at baseline, before surgery and 6 months after surgery.

    Measured: 5 years

  5. Determine the effect of FMD on local immunomodulation and tumor immunity

    By analyzing the immune-composition and gene-expression profile using multispectral Vectra imaging and Nanostring analyses respectively, in tumor samples taken at baseline (diagnostic), after 4 cycles and resection specimen

    Measured: 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2022
  2. Study start17 Mar 2023
  3. Primary completion1 Jan 2024 (estimated)
  4. Study completion1 Jan 2024 (estimated)

Why it stopped: fultility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05503108
Sponsor's protocol ID
NL80749.058.22 DIRECT 2
Other IDs
P22.028, BOOG 2022-01
Acronym
DIRECT-2
Status last verified
Nov 2023
First submitted
24 Jul 2022
Last updated
22 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32576828

  • 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.

    PubMed 33179154

  • 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.

    PubMed 31113478

  • 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.

    PubMed 27411588

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fasting Mimicking diet program in people with Fasting Mimicking Diet and HER2-negative Breast Cancer, run by Leiden University Medical Center at 7 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological response rate (pCR). Both percentage of pCR and 90-100% tumor loss according to Miller & Payne (time frame: 4.5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05503108, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.

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