Clinical trial NCT05748704: Metabolic and Immunological Effects of a Modified Fasting Regimen in Cancer Patients
Official title: Phase I / II Single Arm Study: Metabolic and Immunological Effects of a Modified Fasting Regimen in Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cancer
Keywords: fasting
short-term modified fasting
Lead sponsor: University of Genova
Sponsor class: OTHER
First posted: 2023-03-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: STMF is a 5-day low-calorie and low-protein (totally plant-based) diet that involves a short-term modified fast.
Primary purpose: OTHER

Brief 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Effects of the STMF on IGF1 and IGFBP1
timeFrame: month 1-12
measure: Effects of the STMF on IGFBP3
timeFrame: month 1-12
measure: Effects of the STMF on Interleukin-6 (IL-6), interleukin-1 beta (IL1-beta) and tumor necrosis factor-alpha (TNF-alpha)
timeFrame: month 1-12
measure: Effects of the STMF on insulin
timeFrame: month 1-12
measure: Effects of the STMF on adiponectin
timeFrame: month 1-12
measure: Effects of the STMF on leptin
timeFrame: month 1-12
Secondary outcomes:
measure: Percentage of prescribed diet consumed and intake of any extra food
timeFrame: 3 to 8 weeks depending on the patient's therapy
measure: Quantification of emergent adverse events
timeFrame: 3 to 8 weeks depending on the patient's therapy
measure: Body Weight
timeFrame: 3 to 8 weeks depending on the patient's therapy
measure: Effect of STMF on circulating tumor DNA
timeFrame: month 1-12
measure: Effect of the STMF on the intestinal microbiome
timeFrame: month 1-3
measure: Phase Angle (PA)
timeFrame: 3 to 8 weeks depending on the patient's therapy
measure: Handgrip strength
timeFrame: 3 to 8 weeks depending on the patient's therapy
measure: Effect of cycles of STMF on leukocyte subpopulations
timeFrame: month 1-12
Other outcomes:
Locations:
city: Genova
country: Italy
facility: San Martino Hospital
Study officials:
affiliation: Universita degli Studi di Genova
name: Alessio Nencioni, MD
role: PRINCIPAL_INVESTIGATOR
References: