Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Participants will receive 16 hours of fasting, 8 hour regular feeding for 5 days a week starting 2 days prior to chemotherapy.

Participants will receive standard of care dietary recommendations and will provide a 3-day diet diary at study enrollment and during cycles 2 and 3.

Intermittent fasting (IF) also known as time restricted eating regimen consisting of 16 hours of fasting and 8 hours of ad libitum feeding for 5 days followed by ad libitum feeding for 2 days has been proposed. With this type of intervention, there are no dietary restrictions to the type or quality of food and it decreased daily energy intake by 20%. Participants will be asked to follow an IF schedule consisting of 16 hour of continuous fasting per day for 5 days a week. This will be started 2 days prior to chemotherapy (cycle 2).

Intermittent Fasting

Chemotherapy will be given as standard treatment every 3 weeks (21 days) and continue for 3 to 4 cycles per routine care. As chemotherapy is not part of this research study, participants will begin standard chemotherapy as decided by their physician.

Neoadjuvant chemotherapy

Mariam AlHilli, MD

Jackie Ludwig

The goal of this clinical trial is to see if timed fasting (periods of time that you don't eat) in participants who are receiving chemotherapy prior to surgery is achievable, safe and can improve quality of life, symptoms and outcomes (results) compared to participants who receive standard dietary recommendations in individuals being treated for epithelial ovarian cancer . The main questions it aims to answer are:

* Is it feasible to use intermittent fasting during neoadjuvant chemotherapy?
* Is it safe to use intermittent fasting during neoadjuvant chemotherapy?
* Do participants find it acceptable to use intermittent fasting during neoadjuvant chemotherapy?

Researchers will compare participants who receive standard dietary recommendations to see which method is more achievable, safe, and able to improve quality of life, symptoms and outcomes.

Participants will:

* Receive either the fasting intervention (schedule of times when you do not eat) or standard diet recommendations for 6-9 weeks prior to your surgery starting with the second cycle of chemotherapy.
* All participants will be asked to complete chemotherapy and surgery, cancer imaging, baseline screening tests, nutritional assessments, food diaries, blood tests, and surveys about wellbeing.
* Participants in the intervention group will be asked to follow a fasting schedule that consists of not eating for 16 hours a day followed by normal eating for the remaining 8 hours of the day for 5 days in a row followed by 2 days of regular eating each week.

The quality of diet can affect the biology of cancer. For example, evidence implies a high fat/ Western diet may impose adverse events on ovarian cancer outcomes, and the potential that the gut microbiome alterations secondary to dietary changes may impact tumor responsiveness to treatment and outcomes. This study seeks to clarify the effect of dietary intervention on the tumor and gut microbiome and ovarian cancer biology. The objectives of this study include:

* Primary: To test the feasibility and safety of IF during neoadjuvant chemotherapy (including effects on body composition)
* Secondary: To measure the effects of IF on participant reported outcomes, chemotherapy toxicity and quality of life.
* Exploratory: To test the effect of IF on pathologic response, systemic inflammatory and immune responses, microbial diversity and metabolic pathway alterations.

Participants' cross-sectional skeletal muscle areas will be measured. Measurements will be performed on CT scans obtained within 4-6 weeks of treatment initiation (with a 7-day screening window) by a fellowship-trained, experienced radiologist and imaging specialist in consensus who will be blinded to participant clinical variables and treatment.

Fasting During Neoadjuvant Chemotherapy in Patient With Epithelial Ovarian Cancer

The Feasibility, Safety, and Clinical Outcomes of Fasting During Neoadjuvant Chemotherapy in Patients With Epithelial Ovarian Cancer

All collected participant data will be shared through publication including clinical data, laboratory results, CT data, qualitative data (questionnaire's) in additional, molecular data, histologic data, treatment response after statistical analysis. All data will be shared without participant identifiers.

Participants will be assessed for intermittent fasting compliance which will be measured by metabolic laboratory tests (serum glucose) prior to each chemotherapy.

Participants will be assessed for intermittent fasting compliance which will be measured by metabolic laboratory tests (ketone) prior to each chemotherapy.

Participants will be assessed for intermittent fasting compliance which will be measured by metabolic laboratory tests (IGF-1) prior to each chemotherapy.

Participants will be assessed for intermittent fasting compliance which will be measured by metabolic laboratory tests (insulin) prior to each chemotherapy.

Participants will be assessed for intermittent fasting compliance which will be measured by metabolic laboratory tests (ketone) prior to each chemotherapy. which will be measured by metabolic laboratory tests (serum glucose, ketone, IGF-1, and insulin) prior to each chemotherapy.

Participants will be assessed for intermittent fasting compliance which will be measured by a self-reported compliance checklist assessment.

Participants will be assessed for intermittent fasting compliance which will be measured a 3-food diary submitted during each dietitian in person visit.

Pre- and post- treatment body composition will be assessed by Computed Tomography scans.

Participants will undergo evaluation of chemotherapy related toxicity (according to Common Terminology Criteria for Adverse Events \[CTCAE version 5.0\]).

Participants that undergo an additional cycle of chemotherapy will undergo evaluation of chemotherapy related toxicity (according to Common Terminology Criteria for Adverse Events \[CTCAE version 5.0\]).

Participants will undergo evaluation of chemotherapy related toxicity (according to Common Terminology Criteria for Adverse Events \[CTCAE version 5.0\]),

Participants will complete Edmonton Symptom Assessment Questionnaires (ESAS) at enrollment. The ESAS assesses pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing, and shortness of breath. Responses are scored to produce a physical component summary and a mental component summary on a scale from 0 to 100, with higher scores indicative of better functional status.

Participants will complete Edmonton Symptom Assessment Questionnaires (ESAS). The ESAS assesses pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing, and shortness of breath. Responses are scored to produce a physical component summary and a mental component summary on a scale from 0 to 100, with higher scores indicative of better functional status.

Participants will complete Study Short Form-12 Health Survey (SF-125) at enrollment. The SF-12 measures physical and mental health status. Responses are scored to produce a physical component summary and a mental component summary on a scale from 0 to 100, with higher scores indicative of better functional status.

Participants will complete Study Short Form-12 Health Survey (SF-125) day 1 cycle 2. The SF-12 measures physical and mental health status. Responses are scored to produce a physical component summary and a mental component summary on a scale from 0 to 100, with higher scores indicative of better functional status.

Participants will complete Study Short Form-12 Health Survey (SF-125) day 1 cycle 3. The SF-12 measures physical and mental health status. Responses are scored to produce a physical component summary and a mental component summary on a scale from 0 to 100, with higher scores indicative of better functional status.

Participants will complete Study Short Form-12 Health Survey (SF-125) post treatment. The SF-12 measures physical and mental health status. Responses are scored to produce a physical component summary and a mental component summary on a scale from 0 to 100, with higher scores indicative of better functional status.

Quality of life questionnaires will be distributed at enrollment and will be compared between IF and control groups. Quality of life will be measured by Quality of life will be measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). EORTC QLQ-C30 is a 30 item questionnaire. Higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.

Functional Assessment of Cancer Therapy- Ovarian (FACT-O) will be administered post treatment and will be compared between IF and control groups. FACT-O is a 39 item questionnaire with a 5 point Likert-type scale. Scores range from 0-156. The higher the score, the better the quality of life.

Functional Assessment of Cancer Therapy- Ovarian (FACT-O) will be administered at enrollment and will be compared between IF and control groups. FACT-O is a 39 item questionnaire with a 5 point Likert-type scale. Scores range from 0-156. The higher the score, the better the quality of life.

Acceptability of intervention Measure (AIM) questionnaire will be administered IF participants. AIM has 4 item psychometric assessment times measuring acceptability of intervention. Scale values range from 1 to 5. Overall scores that are lower indicating lower acceptability, and higher scores indicating greater acceptability, appropriateness, and feasibility.

Case Comprehensive Cancer Center

Skin and Connective Tissue Diseases

Breast Neoplasms

Melanoma

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

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.

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

Filippo De Braud, Professor

Claudio Vernieri, MD

Claudio Vernieri, M.D., Ph.D.

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.

Preclinical evidences suggest that reducing the concentration of blood metabolites and growth factors reduces the in vivo growth of several tumor models, while protecting normal tissues from the cytotoxic effects of chemotherapeutical treatments. In recent years, a plant-based, calorie-restricted, low-carbohydrate, low-protein diet, also known as Fasting Mimicking Diet (FMD), has been proposed as a potential anticancer dietary intervention. The FMD is safe when administered cyclically (every 21-28 days) to healthy volunteers, and is capable of significantly reducing the concentration of plasma glucose, serum insulin and IGF-1, while increasing levels of plasma IGFBPs and ketone bodies. The FMD has been shown to inhibit the in vivo growth of several tumor models, including breast cancer and melanoma mice models. The anticancer effects of the FMD are likely mediated by two concomitant mechanisms: 1) one direct anticancer effect that is mediated by the inhibition of energy production and anabolic pathways, such as protein and fatty acid synthesis, in cancer cells; 2) one indirect effect that is mediated by the activation of antitumor immunity, with the result of enhanced tumor infiltration by cytotoxic CD8+ T-lymphocytes and reduced infiltration by immunosuppressive populations. According to the currently accepted model, the anticancer and immunomodulatory effects of the FMD mostly derive from the reduction of circulating glucose, insulin and IGF-1 levels, and a parallel increase of ketone body and IGF-1 binding protein concentration. However, recent observations in healthy volunteers and cancer patients, suggest that FMD-mediated changes in many other metabolites, such as specific amino acids or fatty acids, could contribute to the cell-autonomous or immune-mediated anticancer effects of the FMD. While the study of the effects of the FMD in combination with standard treatments (e.g. chemotherapy, molecular targeted therapy) in advanced cancers represents the final objective of the ongoing studies, fully uncovering the metabolic and immunological effects of the FMD alone is essential to design future combination studies. From this perspective, the pre- and post-operative clinical settings in cancer patients who are not candidate to other medical treatments represent an ideal context to assess the effects of the FMD without other confounding factors. This trial primarily aims to assess the immunological and metabolic changes induced by the 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.

Clinical trials with a single arm and three cohorts of patients

Impact of Dietary Intervention on Tumor Immunity: the DigesT Trial

Impact of Dietary Intervention on Tumor Immunity: the DigesT Trial.

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

Phenotypic modifications in PBMCs, as detected by by 10-colors citofluorimetry and single-cell "mass cytometry" (CyTOF)

Functional modifications in PBMCs, as detected by by 10-colors citofluorimetry and single-cell "mass cytometry" (CyTOF)

Functional modifications in tumor-infiltrating lymphocytes, as detected by by 10-colors citofluorimetry and single-cell "mass cytometry" (CyTOF)

Phenotypic modifications in tumor-infiltrating lymphocytes, as detected by by 10-colors citofluorimetry and single-cell "mass cytometry" (CyTOF)

Functional modifications of immune cell populations in LNs, as detected by single-cell "mass cytometry" (CyTOF).

Gene expression profiling (through mRNA quantification) in tumor cells (Cohort A).

Gene expression profiling (through mRNA quantification) in PBMCs and immune cell populations inside lymph nodes (Cohort B).

miRNA profiling in tumor cells (Cohort A)

miRNA profiling in PBMCs and immune cell populations inside lymph nodes (Cohort B).

Changes in the expression of selected metabolic genes (including hexokinase 1, phosphofructokinase 1, pyruvate kinase 2) through mRNA quantification in PBMCs before and after the FMD.

FMD-induced changes in blood (glucose, triglycerides, fatty acids, cholesterol, amino acids)

FMD-induced changes in urine metabolites (ketone bodies)

FMD-induced changes in serum growth factors.

Qualitative changes in the type of tumor-infiltrating immune cell populations before and after the diet in breast cancer patients undergoing curative surgery (Cohort A).

Quantitative changes in the number of tumor-infiltrating lymphocytes, machrophages, MDSCs before and after the diet in breast cancer patients undergoing curative surgery (Cohort A).

Changes in tumor proliferation index (Ki67) IHC in breast cancer patients (Cohort A).

Changes in tumor cell apoptosis (caspase 3 by IHC) in breast cancer patients (Cohort A).

Changes in tumor levels of glycolytic enzymes by IHC (Glut1, HK1, PFK1/2, PK2) in breast cancer patients (Cohort A).

Changes in expression of estrogen and/progesterone receptor and HER2 oncoprotein by IHC in breast cancer patients (Cohort A).

Changes in the type of immune cells (CD8+ T-lymhocytes, CD 4+ lymphocytes, Treg) found in lymph node suspensions of melanoma patients undergoing one FMD cycle before lymph node dissection (Cohort B).

Quantitative changes in the absolute and relative amount of immune cell populations in lymph node suspensions of melanoma patients undergoing one FMD cycle before lymph node dissection (Cohort B).

Changes in genome-wide DNA methylomic profiles with high-density arrays in lymph node specimens from patients undergoing the FMD before surgery (Cohorts A and B).

Changes in genome-wide DNA methylomic profiles with high-density arrays in tumor specimens from patients undergoing the FMD before surgery (Cohorts A and B).

Changes in type of gut bacteria populations, as detected through 16S ribosomal RNA sequencing

Short-term (before vs after each FMD cycle) modification of blood nutritional parameters (levels of plasma cholesterol, prealbumin, transferrin, total lymphocytes)

Long-term (along subsequent FMD cycles) modification of blood nutritional parameters (levels of plasma cholesterol, realbumin, transferrin, total lymphocytes)

Short-term and long-term modification of BMI

FMD-induced changes in neutrophils, macrophages, lymphocytes

Assessment of patient compliance to the FMD, as measured by quantifying the number of major and minor deviations of patients' diet relative to the prescribed FMD scheme

Assessment of FMD tolerability, as defined by the occurrence of G3-G4 adverse events, or serious adverse events (SAEs)

Correlation between FMD-induced changes in serum metabolites and changes in PBMCs, their activation status, and characteristics of tumor cell and immune infiltrate.

Correlation between FMD-induced metabolic and immunological changes with patient diet evaluated at study enrollment through food diaries.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fasting During Neoadjuvant Chemotherapy in Patient With Epithelial Ovarian Cancer	NCT06386887	Epithelial Ovar...	Intermittent Fa... Neoadjuvant che...	18 Years -	Case Comprehensive Cancer Center
Impact of Dietary Intervention on Tumor Immunity: the DigesT Trial	NCT03454282	Breast Cancer Melanoma, Malig...	FMD	18 Years - 75 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Fasting During Neoadjuvant Chemotherapy in Patient With Epithelial Ovarian Cancer	NCT06386887	Epithelial Ovar...	Intermittent Fa... Neoadjuvant che...	18 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for fasting mimicking diet (fmd)