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

Breast Cancer Clinical Trial

— DIRECT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02126449
• Other study ID #: NL44684.058.13
• Secondary ID: BOOG2013-04p13.1
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: February 2014
• Est. completion date: November 2018

Study information

• Verified date: October 2019
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: November 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Fasting Mimicking Diet
• Neoadjuvant Chemotherapy
• Pathological Complete Response

Intervention

Other:
• Fasting mimicking diet

Locations

Country	Name	City	State
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	Leids Universitair Medisch Centrum	Leiden	Zuid-holland
Netherlands	Bronovo Hospital	The Hague
Netherlands	Haga Hospital	The Hague
Netherlands	VieCurie Hospital	Venlo
Netherlands	Lange Land Hospital	Zoetermeer
Netherlands	Isala	Zwolle

Sponsors (4)

Lead Sponsor	Collaborator
Leiden University Medical Center	Amgen, Borstkanker Onderzoek Groep, Pink Ribbon Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Protein profiles and cytokines used as biomarker to predict treatment outcome		4 years
Other	Quantification of chemotherapy-induced DNA damage in leukocytes (with ?-H2AX modification and comet assay).		3years
Other	Quantification of nutrient sensing system gene expression (with western blot).		3 years
Primary	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	2 years
Primary	The percentage of pCR.	Phase III	4 years
Secondary	Clinical response measured by MRI (RECIST1.1) after 4 cycles chemotherapy.		4 years
Secondary	Grade I/II side effects of chemotherapy according to NCI CTCAE v4.03.		4 years
Secondary	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.		4 years
Secondary	DNA damage, apoptosis, immunology and nutrient sensing system activity in the tumor.		5 years
Secondary	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).		4 years
Secondary	Long term efficacy of treatment (DFS, OS).		4years
Secondary	Hormone receptor percentage, Ki67 and immunologic tumor profile and tumor/stroma ratio as predictive biomarker		4 years
Secondary	SNPs used as biomarker to predict treatment outcome.		5 years

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