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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05748704
• Other study ID #: STMF
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2021
• Est. completion date: November 1, 2025

Study information

• Verified date: February 2023
• Source: University of Genova
• Contact: Alessio Nencioni, MD
• Phone: +39 010 353
• Email: alessio.nencioni[@]unige.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 1, 2025
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cancer

Intervention

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.

Locations

Country	Name	City	State
Italy	San Martino Hospital	Genova

Sponsors (1)

Lead Sponsor	Collaborator
University of Genova

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effects of the STMF on IGF1 and IGFBP1	IGF1 and IGFBP1 dosage (µg/l)	month 1-12
Primary	Effects of the STMF on IGFBP3	IGFBP1 dosage (mg/l)	month 1-12
Primary	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
Primary	Effects of the STMF on insulin	Insulin dosage (mLU/L)	month 1-12
Primary	Effects of the STMF on adiponectin	Adiponectin dosage (µg/ml)	month 1-12
Primary	Effects of the STMF on leptin	Leptin dosage (ng/ml)	month 1-12
Secondary	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
Secondary	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
Secondary	Body Weight	Weight is used to calculate the BMI as weight (kg)/height (m2).	3 to 8 weeks depending on the patient's therapy
Secondary	Effect of STMF on circulating tumor DNA	It will be assessed by measuring circulating tumor DNA - ctDNA	month 1-12
Secondary	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
Secondary	Phase Angle (PA)	PA is a linear method of measuring the relationship between Electrical Resistance (Rz) and Reactance (Xc) both expressed in ohms (O). 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
Secondary	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
Secondary	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