Clinical Trials /

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

NCT02126449

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer
  • Official Title: DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: NL44684.058.13
  • SECONDARY ID: BOOG2013-04
  • SECONDARY ID: p13.135
  • NCT ID: NCT02126449

Conditions

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

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Fasting mimicking dietExperimentalShort term fasting using Fasting mimicking diet around neoadjuvant chemotherapy (AC>T)
    regular dietNo InterventionStandard neoadjuvant chemotherapy (AC>T)

      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
            
      Maximum Eligible Age:70 Years
      Minimum Eligible Age:18 Years
      Eligible Gender:Female
      Healthy Volunteers:No

      Primary Outcome Measures

      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
      Safety Issue:
      Description:Phase II

      Secondary Outcome Measures

      Measure:Clinical response measured by MRI (RECIST1.1) after 4 cycles chemotherapy.
      Time Frame:4 years
      Safety Issue:
      Description:
      Measure:Grade I/II side effects of chemotherapy according to NCI CTCAE v4.03.
      Time Frame:4 years
      Safety Issue:
      Description:
      Measure: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
      Safety Issue:
      Description:
      Measure:DNA damage, apoptosis, immunology and nutrient sensing system activity in the tumor.
      Time Frame:5 years
      Safety Issue:
      Description:
      Measure: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
      Safety Issue:
      Description:
      Measure:Long term efficacy of treatment (DFS, OS).
      Time Frame:4years
      Safety Issue:
      Description:
      Measure:Hormone receptor percentage, Ki67 and immunologic tumor profile and tumor/stroma ratio as predictive biomarker
      Time Frame:4 years
      Safety Issue:
      Description:
      Measure:SNPs used as biomarker to predict treatment outcome.
      Time Frame:5 years
      Safety Issue:
      Description:

      Details

      Phase:Phase 2/Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Leiden University Medical Center

      Last Updated