Impact of Dietary Intervention on Tumor Immunity: the DigesT Trial

NCT03454282 | Unknown

• 2 other identifiers: INT157/17B42F17000260006
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This trial aims to assess the immunological and metabolic changes induced by the Fasting Mimicking Diet (FMD) in the pre-operative and post-operative setting in breast cancer and melanoma patients. Three cohorts of patients will be enrolled: 1) Cohort A: patients with resectable breast cancer (cT1N0M0 stage or cT1cN1M0-cT2cN0M0 stages not requiring pre-operative systemic treatment at the judgment of the investigator) who are candidate to curative surgery; 2) Cohort B: patients with malignant melanoma patients candidate to dissection of the lymph node basin because of a positive sentinel lymph node (stage IIIA-IIIB-IIIC); 3) Cohort C: patients with resected malignant melanoma (including radicalization and, in case, lymph node dissection) who are not candidate to any adjuvant treatment, but only to clinical and radiological follow-up (stage IIB-IIC). Patients in cohorts A and B will undergo one 5-days FMD cycle about 13-15 days before surgical removal of primary tumor (breast) or lymph nodes (breast, melanoma). Patients in cohort C will undergo 4 consecutive FMD cycles every 28 days, starting one month after surgery.

Conditions

Breast Cancer; Melanoma, Malignant

Keywords

Breast; Cancer; Malignant; Melanoma; Fasting Mimicking Diet (FMD); Tumor; Immunity; Metabolic Effects; Immunological Effects

Outcome Measures

Primary Outcomes (1)

• Absolute and relative changes in PBMCs

  Absolute and relative changes in PBMCs by 10-color cytofluorimetry before and after the FMD.

  3 years

Secondary Outcomes (33)

• Phenotypic modifications in PBMCs

  3 years

• Functional modifications in PBMCs

  3 years

• Functional modifications in tumor-infiltrating lymphocytes

  3 years

• Phenotypic modifications in tumor-infiltrating lymphocytes

  3 years

• Functional modifications of immune cell population in LNs

  3 years

Study Arms (1)

FMD Arm

EXPERIMENTAL

The intervention consists in 5-day FMD (Fasting Mimicking Diet) to be followed for one cycle (Cohorts A and B) or for 4 consecutive every-four week cycles postoperatively.

Other: FMD

Interventions

FMD OTHER

The Fasting Mimicking Diet (or FMD) consists in a 5-day plant-based, low-calorie (about 600 Kcal on day 1, followed by about 300 KCal/day on days 2 to 5), low-carbohydrate low-protein diet

Also known as: Fasting Mimicking Diet

FMD Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 and ≤ 75 years.
• Evidence of a personally signed and dated informed consent document (ICD) indicating that the patient has been informed of all pertinent aspects of the study before enrollment and FMD prescription.
• Willingness and ability to comply with the FMD protocol, the scheduled visits, treatment plans, laboratory tests and other procedures.
• Histologically confirmed diagnosis of invasive breast cancer candidate to curative surgery (Cohort A), or resected malignant melanoma requiring dissection of the regional lymph node basin for sentinel lymph node involvement (Cohort B), or malignant melanoma treated with curative surgery (including, in case, lymph node removal and lymph node dissection) (Cohort C). For breast cancer patients, any biological subgroup (including estrogen receptor-positive, HER2-positive, triple-negative breast cancer) will be admitted; HER2-positive tumors will be defined on the basis of an IHC score of 3, or a score of 2 with ISH evaluation indicative of gene amplification.
• Availability of archival FFPE tissue blocks of primary breast cancer (Cohort A) or melanoma (Cohort B, Cohort C).
• Presence of an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Presence of adequate bone marrow and organ function as defined by the following laboratory values:
• ANC ≥ 1.5 x 109/l
• platelets ≥ 100 x 109/l
• hemoglobin ≥ 9.0 g/dl
• calcium (corrected for serum albumin) within normal limits or ≤ grade 1 according to NCI-CTCAE version 4.03 if not clinically significant
• potassium within the normal limits, or corrected with supplements
• creatinine \< 1.5 ULN
• blood uric acid \< 10 mg/dl
• ALT and AST ≤ 2.5 x ULN

You may not qualify if:

• Prior systemic treatment for breast cancer or melanoma.
• Diagnosis of a concurrent malignancy other than breast cancer or melanoma, or malignancy other than breast cancer or melanoma diagnosed within 5 years of treatment enrollment, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Body Mass Index (BMI) \< 20 Kg/m2.
• Anamnesis of alcohol abuse.
• Unintentional weight loss ≥ 5% in the last three months, unless the patient has a BMI \> 25 Kg/m2 at study enrollment. Intentional weight loss is permitted if \< 10% in the last three months and patient BMI is \> 22 kg/m2.
• Severe heart, liver, pulmonary, kidney comorbidities.
• Current status of pregnancy or lactation, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL).
• Active HBV or HCV infection.
• Severe infections within 4 weeks prior to FMD initiation, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Active autoimmune diseases that require systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• History of recent diagnosis of hypothyroidism for which replacement therapy (eg., thyroxine) and blood endocrine profile are not stabilized yet.
• Established diagnosis of diabetes mellitus type I or diabetes mellitus type II that requires pharmacological treatment (including, but not limited to, insulin, insulin secretagogues and metformin).
• Severe impairment of the gastrointestinal (GI) function or GI disease that may alter the digestion and absorption of nutrients during the re-feeding phase (e.g. active ulcerative diseases of the stomach or intestine, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known history of Human Immunodeficiency Virus (HIV) infection.
• Clinically significant heart disease and/or recent cardiac events including:

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• National Health Research Institutes, Taiwan: collaborator
• Centro de Investigación en Nanomateriales y Nanotecnología (CINN): collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Martin-Luther-Universität Halle-Wittenberg: collaborator
• University of Milan: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Related Publications (20)

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• Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 18.

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MeSH Terms

Conditions

Breast Neoplasms; Melanoma; Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms

Study Officials

• Filippo De Braud, Professor

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Filippo De Braud, Professor

CONTACT

0039 02/23902148; filippo.debraud@istitutotumori.mi.it

Claudio Vernieri, MD

CONTACT

0039 02/23903066; claudio.vernieri@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Clinical trials with a single arm and three cohorts of patients

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: March 5, 2018
• Study Start: July 1, 2018
• Primary Completion: May 30, 2020
• Study Completion: December 31, 2020
• Last Updated: February 26, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)