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AzTrials

Fasting Mimicking DietPhase 2/3DIRECTNCT02126449

DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer

A Phase 2/3 study testing Fasting mimicking diet in people with Fasting Mimicking Diet and Breast Cancer, run by Leiden University Medical Center at 15 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Preclinical studies provide strong support for the concept that fasting evokes resistance to multiple forms of stress. Fasting reduces plasma levels of growth factors and modulates intracellular nutrient sensing systems, thereby diverting energy from growth to maintenance. Read more about this study

Who is it for?
Ages 18 to 70 years, women only
What is being tested?
Fasting mimicking diet
Could I receive a placebo?
No, everyone receives an active treatment
How many people
131 participants
Where
15 sitesNetherlands
Study dates
Feb 2014to Nov 2018
Phase
Phase 2/3
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 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female patients with stage II or III (cT1cN+ or ≥T2 any cN, cM0) breast cancer receiving neoadjuvant AC-T
  • Measurable disease (breast and/or lymph nodes)
  • HER2 negative core biopsy Age ≥18 years
  • WHO performance status 0-2
  • 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
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  • Adequate renal function: the calculated creatinine clearance should be ≥50 mL/min
  • Patients must be accessible for treatment and follow-up
  • Written informed consent according to the local Ethics Committee requirements
  • Willing to fill in quality of life questionnaires
  • Able to read and write in Dutch

Who cannot join

  • History of breast cancer (invasive or non-invasive)
  • Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
  • Serious other diseases such as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
  • Diabetes Mellitus
  • Body mass index (BMI) < 19 kg/m2
  • Pregnancy or lactating
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  • Significant food allergies which would make the subject unable to consume the food provided (ex: nuts or soy)
  • Any metabolic disorders that may affect gluconeogenesis or adaptation to short fasting periods.
  • Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Netherlands15 sites

  • Medisch Centrum Alkmaar

    Alkmaar

  • OLVG

    Amsterdam

  • Alexander Monro hospital

    Bilthoven

  • Amphia Hospital

    Breda

  • Deventer Hospital

    Deventer

  • Ziekenhuis Gelderse Valei

    Ede

  • , Catharina ziekenhuis Hospital

    Eindhoven

  • Kennemer gasthuis

    Haarlem

  • Medisch Centrum Leeuwarden

    Leeuwarden

  • Leids Universitair Medisch Centrum

    Leiden, South Holland, 2333ZA

  • Bronovo Hospital

    The Hague

  • Haga Hospital

    The Hague

  • VieCurie Hospital

    Venlo

  • Lange Land Hospital

    Zoetermeer

  • Isala

    Zwolle

Other trials in Netherlands

About this study

Preclinical studies provide strong support for the concept that fasting evokes resistance to multiple forms of stress. Fasting reduces plasma levels of growth factors and modulates intracellular nutrient sensing systems, thereby diverting energy from growth to maintenance. Accordingly, the currently available preclinical evidence suggests that short-term fasting protects normal cells against the perils of chemotherapy. In contrast, cancer cells are not protected, as a result of their self-sufficiency in growth signals. This phenomenon is termed Differential Stress Resistance (DSR). DSR reduces the severity of toxic side-effects of chemotherapy and interestingly, it simultaneously renders cancer cells more vulnerable to chemotherapeutics. Importantly, extensive preclinical evidence and preliminary clinical data indicate that a specifically designed very low calorie, low amino acid substitution diet ("Fasting Mimicking Diet, FMD") has effects on cancer therapy that are very similar to those of fasting. This study aims to evaluate the impact of the FMD on tolerance to and efficacy of neoadjuvant chemotherapy in women with stage II or III breast cancer.

Being tested
Fasting mimicking diet
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Fasting mimicking dietOther

Study groups in NCT02126449
Study groupRoleWhat they receive
Fasting mimicking dietExperimentalShort term fasting using Fasting mimicking diet around neoadjuvant chemotherapy (AC>T)
Receives: Other: Fasting mimicking diet
regular dietNo interventionStandard neoadjuvant chemotherapy (AC>T)

What is being measured

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

  1. The percentage of patients with grade III/IV toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version (NCI CTCAE) v4.03.

    Phase II

    Measured: 2 years

  2. The percentage of pCR.

    Phase III

    Measured: 4 years

Secondary outcomes (8)

  1. Clinical response measured by MRI (RECIST1.1) after 4 cycles chemotherapy.

    Measured: 4 years

  2. Grade I/II side effects of chemotherapy according to NCI CTCAE v4.03.

    Measured: 4 years

  3. Metabolic (Glucose, insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein 3 (IGF-BP3), free thyroxin (FT4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH)) and inflammatory response (CRP) to chemotherapy.

    Measured: 4 years

  4. DNA damage, apoptosis, immunology and nutrient sensing system activity in the tumor.

    Measured: 5 years

  5. Patient's quality of life (using EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires), burden of therapy noted by a visual analogue scale (VAS) (Distress Thermometer) and differences of Illness Perceptions (B-IPQ).

    Measured: 4 years

  6. Long term efficacy of treatment (DFS, OS).

    Measured: 4years

  7. Hormone receptor percentage, Ki67 and immunologic tumor profile and tumor/stroma ratio as predictive biomarker

    Measured: 4 years

  8. SNPs used as biomarker to predict treatment outcome.

    Measured: 5 years

Timeline

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

  1. First posted30 Apr 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completionNov 2018
  4. Study completionNov 2018

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
131 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02126449
Sponsor's protocol ID
NL44684.058.13
Other IDs
BOOG2013-04, p13.135
Acronym
DIRECT
Status last verified
Oct 2019
First submitted
14 Feb 2014
Last updated
24 Oct 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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, 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

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Fasting mimicking diet in people with Fasting Mimicking Diet and Breast Cancer, run by Leiden University Medical Center at 15 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 9 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: finished, as of the sponsor's last update on 24 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The percentage of patients with grade III/IV toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version (NCI CTCAE) v4.03. (time frame: 2 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 NCT02126449, which also lists 2 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 24 Oct 2019.

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