Metabolic and Immunological Effects of a Modified Fasting Regimen in Cancer Patients

Phase I / II Single Arm Study: Metabolic and Immunological Effects of a Modified Fasting Regimen in Cancer Patients

This is a single-arm prospective pilot study assessing the metabolic and immunologic effects of a modified fasting regimen in cancer patients with different cancer types and concomitant anticancer treatment.

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Other: Short-term modified fasting

Detailed Description

A single-arm phase II clinical trial of a short-term modified fasting regimen (STMF) is proposed to be conducted in 100 patients with solid tumors who are candidates to receive active medical or radiotherapy treatment (or with medical treatment or radiotherapy already ongoing). Cancer treatment can be adjuvant or palliative. Patients with haematological tumors are also included. Enrolment is also foreseen for patients with haematological tumors who are not undergoing active treatment yet, but are followed with a watchful waiting approach (e.g. patients with low-risk B-CLL or low-risk follicular lymphoma). Finally, enrolment is also open to patients with relapsing forms of non-melanoma skin cancers (e.g. basalioma, epithelioma).

The primary endpoint of the study is to evaluate the effects of a STMF on the circulating levels of factors with pro- or anti-oncogenic activity (including insulin, IGF1, IGFBP1, IGFBP3 , leptin, adiponectin, IL-6, TNF-alpha, IL1beta), as well as the effect of STMF cycles on leukocyte subpopulations with a role in the control of tumor growth, such as regulatory T cells, the "myeloid-derived suppressor cells" (MDSC) as well as NK cells, and on stem cell pools (e.g. hematopoietic stem cells, endothelial stem cells, mesenchymal stem cells).

The STMF regimen that is applied is a 5-day low-calorie and low-protein diet. Patients undergo a medical exam/history collection and a nutritional assessment (body weight, handgrip strenght and bioimpedance measurement) at baseline and then at the visits that precede every cycle of STMF (i.e. once every three weeks or monthly, depending on the therapeutic regimen the patient is undergoing, and in any case no more frequently than once every three weeks - eg when combined with q21 chemotherapy regimens). Adverse events are recorded at each visit in accordance with NCI-CTCAE version 5.0. P

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alessio Nencioni, MD; Phone Number: 1 +39 010 353; Email: alessio.nencioni@unige.it

Study Locations

• Italy
  • Genova, Italy, 16132
    • Recruiting
    • San Martino Hospital
    • Contact: Alessio Nencioni, MD; Phone Number: Ext. 8990 +39 010 353; Email: alessio.nencioni@unige.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Age > 18 years
• Patients with solid or hematologic tumors undergoing active treatment (including chemotherapy regimens, hormone therapies, other molecularly targeted therapies - including kinase inhibitors, biologicals or inhibitors of immune checkpoints; patients in whom treatment is already ongoing are also eligible; patients with haematological malignancies who are managed by watchful waiting (e.g. low-risk B-CLL or follicular lymphoma) as well as patients with relapsing forms of non-melanoma skin cancer (basal or squamous cell carcinoma) are also eligible.
• ECOG performance status 0-1
• Adequate organ function
• BMI >21 kg/m2 (with possibility to also enroll patients with 18.5<BMI<21 based on the judgement of the treating physician)
• Low nutritional risk according to nutritional risk screening (NRS)

Exclusion Criteria:

• Age> 65 years [with the possibility to enroll from 65 to 75 years old patients if considered safe by the examining doctor
• Diabetes mellitus;
• BMI <18.5 kg/m2;
• Bio-impedance phase angle <5.0°;
• Medium/high nutritional risk according to NRS;
• Any metabolic disorder capable of affecting gluconeogenesis or the ability to adapt to periods of fasting;
• Ongoing treatment with other experimental therapies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Short-term modified fasting; The STMF regimen consists of a low-calorie diet lasting five days and aimed at providing between 800 and 1,000 kcal/day (tentatively 10% carbohydrates, 15% proteins, 75% lipids).

Other: Short-term modified fasting; STMF regimen consists of a low-calorie diet aimed at providing 800-1,000 kcal/day, lasting five days and with the following composition: 10% carbohydrates, 15% proteins, 75% lipids. During the days of STMF, patients will be required to write down the foods consumed in a food diary in order to calculate calorie and nutrients intake. The STMF regimen will be administered tentatively on a monthly basis (depending on the therapeutic regimen the patient undergoes) and in any case no more frequently than once every three weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of the STMF on IGF1 and IGFBP1	IGF1 and IGFBP1 dosage (μg/l)	month 1-12
Effects of the STMF on IGFBP3	IGFBP1 dosage (mg/l)	month 1-12
Effects of the STMF on Interleukin-6 (IL-6), interleukin-1 beta (IL1-beta) and tumor necrosis factor-alpha (TNF-alpha)	IL-6, IL-1beta and TNF-alpha dosage (pg/ml)	month 1-12
Effects of the STMF on insulin	Insulin dosage (mLU/L)	month 1-12
Effects of the STMF on adiponectin	Adiponectin dosage (μg/ml)	month 1-12
Effects of the STMF on leptin	Leptin dosage (ng/ml)	month 1-12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of prescribed diet consumed and intake of any extra food	It will be assessed using a food diary during 5 days of STMF and is defined as strict adherence to the diet; it is permitted a maximum consumption of 5 Kcal / kg of body weight of extra food on only one of the days of each cycle; or a maximum consumption of 2 Kcal / kg of body weight of extra food in two days of each cycle; or as the reduction of the number of days of the STMF from 5 to 3/4 at most once every three cycles.	3 to 8 weeks depending on the patient's therapy
Quantification of emergent adverse events	It will be assessed monitoring adverse events during STMF according to CTCAE 5.0.	3 to 8 weeks depending on the patient's therapy
Body Weight	Weight is used to calculate the BMI as weight (kg)/height (m2).	3 to 8 weeks depending on the patient's therapy
Effect of STMF on circulating tumor DNA	It will be assessed by measuring circulating tumor DNA - ctDNA	month 1-12
Effect of the STMF on the intestinal microbiome	It will be assessed by comparing fecal samples: the investigators are going to collect simples before and after the first and the third cycle. The analysis will be carried out through the analysis of the 16S rRNA present in the sample. The investigators will analyze if and how bacterial strains change in terms of quantity and quantity after cycles of fasting	month 1-3
Phase Angle (PA)	PA is a linear method of measuring the relationship between Electrical Resistance (Rz) and Reactance (Xc) both expressed in ohms (Ω). PA is detected by a Single Frequency Bioimpedance Analyzer (BIA 101®, Akern, Florence, Italy). Bioelectrical impedance measurements are subsequently processed with the Bodygram Plus® software (Akern, Florence, Italy). PA is an indicator of nutritional status	3 to 8 weeks depending on the patient's therapy
Handgrip strength	Handgrip strength is evaluated with the use of a dynamometer (T.K.K.5001 GRIP A Hand Grip Analogue Dynamometer, Takei, Japan).	3 to 8 weeks depending on the patient's therapy
Effect of cycles of STMF on leukocyte subpopulations	To evaluate the potential impact of fasting on antitumor immune response, we will use multicolor flow cytometry to explore the frequency of myeloid and lymphocytic peripheral blood mononuclear cell (PBMC) populations, with a particular focus on natural killer (NK) cells (CD45+ CD3- CD56+ CD16+ DR+/-), B cells (CD3-CD45+ CD19+), T cells (CD3+ CD45+), NKT cells (CD45+ CD3+ CD56+ CD16+ DR+/-), helper T (Th) cells (CD3+ CD45+ CD4+ DR+/-), cytotoxic T (CTL) lymphocytes (CD3+ CD45+ CD8+ DR+/-), regulatory T (Treg) cells (CD3+ CD45+ CD8+/- CD4+/- CD127- CD25+), exhausted T cells (CD3+ CD45+ CD8+/- CD4+/- CD28-), activated and effector T cells (CD3+ CD45+ CD8+/- CD4+/- CD39+ CD25+ DR+).	month 1-12

Collaborators and Investigators

• Sponsor: University of Genova
• Investigators: Principal Investigator: Alessio Nencioni, MD, Università degli Studi di Genova

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Anticipated): November 1, 2025
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: October 19, 2022
• First Submitted That Met QC Criteria: February 17, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: fasting; short-term modified fasting
• Other Study ID Numbers: STMF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No