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

NCT ID: NCT02126449

Last Updated: 2019-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2018-11-30

Brief 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. 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.

Conditions

Fasting Mimicking Diet; Breast Cancer; Neoadjuvant Chemotherapy; Pathological Complete Response

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fasting mimicking diet

Short term fasting using Fasting mimicking diet around neoadjuvant chemotherapy (AC\>T)

Group Type: EXPERIMENTAL

Fasting mimicking diet

Intervention Type: OTHER

regular diet

Standard neoadjuvant chemotherapy (AC\>T)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Fasting mimicking diet

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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
• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Borstkanker Onderzoek Groep

NETWORK

Sponsor Role: collaborator

Pink Ribbon Inc.

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

J.R. Kroep

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Judith R Kroep, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Hanno Pijl, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Koos JM van der Hoeven, MD PhD Ir

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Leids Universitair Medisch Centrum

Leiden, South Holland, Netherlands

Medisch Centrum Alkmaar

Alkmaar, , Netherlands

OLVG

Amsterdam, , Netherlands

Alexander Monro hospital

Bilthoven, , Netherlands

Amphia Hospital

Breda, , Netherlands

Deventer Hospital

Deventer, , Netherlands

Ziekenhuis Gelderse Valei

Ede, , Netherlands

, Catharina ziekenhuis Hospital

Eindhoven, , Netherlands

Kennemer gasthuis

Haarlem, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Bronovo Hospital

The Hague, , Netherlands

Haga Hospital

The Hague, , Netherlands

VieCurie Hospital

Venlo, , Netherlands

Lange Land Hospital

Zoetermeer, , Netherlands

Isala

Zwolle, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 33179154 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32576828 (View on PubMed)

Related Links

https://www.boogstudycenter.nl

Related Info

Other Identifiers

BOOG2013-04

Identifier Type: OTHER

Identifier Source: secondary_id

p13.135

Identifier Type: OTHER

Identifier Source: secondary_id

NL44684.058.13

Identifier Type: -

Identifier Source: org_study_id