DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer (DIRECT)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02126449 |
Recruitment Status :
Completed
First Posted : April 30, 2014
Last Update Posted : October 24, 2019
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Fasting Mimicking Diet Breast Cancer Neoadjuvant Chemotherapy Pathological Complete Response | Other: Fasting mimicking diet | Phase 2 Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 131 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer |
Actual Study Start Date : | February 2014 |
Actual Primary Completion Date : | November 2018 |
Actual Study Completion Date : | November 2018 |

Arm | Intervention/treatment |
---|---|
Experimental: Fasting mimicking diet
Short term fasting using Fasting mimicking diet around neoadjuvant chemotherapy (AC>T)
|
Other: Fasting mimicking diet |
No Intervention: regular diet
Standard neoadjuvant chemotherapy (AC>T)
|
- 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 ]Phase II
- The percentage of pCR. [ Time Frame: 4 years ]Phase III
- Clinical response measured by MRI (RECIST1.1) after 4 cycles chemotherapy. [ Time Frame: 4 years ]
- Grade I/II side effects of chemotherapy according to NCI CTCAE v4.03. [ Time Frame: 4 years ]
- 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. [ Time Frame: 4 years ]
- DNA damage, apoptosis, immunology and nutrient sensing system activity in the tumor. [ Time Frame: 5 years ]
- 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). [ Time Frame: 4 years ]
- Long term efficacy of treatment (DFS, OS). [ Time Frame: 4years ]
- Hormone receptor percentage, Ki67 and immunologic tumor profile and tumor/stroma ratio as predictive biomarker [ Time Frame: 4 years ]
- SNPs used as biomarker to predict treatment outcome. [ Time Frame: 5 years ]
- Protein profiles and cytokines used as biomarker to predict treatment outcome [ Time Frame: 4 years ]
- Quantification of chemotherapy-induced DNA damage in leukocytes (with γ-H2AX modification and comet assay). [ Time Frame: 3years ]
- Quantification of nutrient sensing system gene expression (with western blot). [ Time Frame: 3 years ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02126449
Netherlands | |
Leids Universitair Medisch Centrum | |
Leiden, Zuid-holland, Netherlands, 2333ZA | |
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 |
Principal Investigator: | Judith R Kroep, MD, PhD | Leiden University Medical Center | |
Principal Investigator: | Hanno Pijl, MD PhD | Leiden University Medical Center | |
Principal Investigator: | Koos JM van der Hoeven, MD PhD Ir | Leiden University Medical Center |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | J.R. Kroep, MD, PhD, Leiden University Medical Center |
ClinicalTrials.gov Identifier: | NCT02126449 |
Other Study ID Numbers: |
NL44684.058.13 BOOG2013-04 ( Other Identifier: BOOG ) p13.135 ( Other Identifier: CME LUMC ) |
First Posted: | April 30, 2014 Key Record Dates |
Last Update Posted: | October 24, 2019 |
Last Verified: | October 2019 |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases |