Impact of "Targeted" Nutritional Apport and Exercise on the Modulation of Metabolic and Immune-related Gene Expression Signatures in Early Breast Cancer (eBC) Patients Candidate to Neoadjuvant Therapy (NAT) (NEOMET)

A Phase II Randomized Trial to Evaluate the Impact of "Targeted" Nutritional Apport and Exercise on the Modulation of Metabolic and Immune-related Gene Expression Signatures in Early Breast Cancer (eBC) Patients Candidate to Neoadjuvant Therapy (NAT)

NEOMET is an exploratory randomized prospective, multicenter study whose primary aim is to explore if metabolomic signatures can be modified by a lifestyle intervention including dietary supplements and physical exercise intervention, in eBC patients candidate to NAT. Eligible patients will be randomised to one of 4 groups: A. NAT, according to molecular subtype; B. NAT plus nutritional supplementation; C. NAT plus supervised physical exercise; D. NAT plus supervised physical exercise plus nutritional supplementation. Nutritional supplementazion will consist of two main long-chain polyunsaturated fatty acids omega-3 (n-3 Lc-PUFA), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) plus a source of palmitoleic acid (hexadecenoic acid).

Study Overview

• Status: Recruiting
• Conditions: Early Breast Cancer; Neoadjuvant Treatment
• Intervention / Treatment: Dietary supplement: omega-3 (n-3 Lc-PUFA), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) plus a source of palmitoleic acid (hexadecenoic acid)

Detailed Description

The primary objectives are: 1. To explore the impact of a lifestyle intervention including dietary supplements and physical exercise on the modulation of metabolomic signatures in eBC patients candidate to NAT; 2. To assess the Omega-3 Index at baseline and before surgery in all patient cohorts. Secondary objectives are: Impact of the combined lifestyle intervention on patient metabolic profile and body composition, by bioelectrical Impedance analysis; assessment of the immunophenotype of lymphocyte subpopulations and their correlation with metabolomic profile and response to therapy; characterization of immune-related and metabolic-related gene-expression signatures in tumor tissue and their correlation with metabolomic profile and response to therapy; evaluation of the pharmacokinetic interactions between nutritional supplementation and chemotherapy; evaluation of pCR in the different treatment arms; changes in health-related QoL (EORTC QLQ-C30, QLQ-BR45, and EQ-5D-5L), and safety and toxicity profiles according to the NCI-CTCAE v.5.0.

Due to explorative intent of the study no formal sample size calculation is provided. A total of 160 consecutive patients will be enrolled into the four arms of the study, with an allocation ratio equal to 1:1:1:1 (40 pts/arm). It can be estimated that the accrual will be completed in 20 months. Data collection, molecular assessments and data analysis with final scientific output are expected to extend the study duration to a total of 26 months.

The following analyses will be performed: - Conversion rate from a poor to a good metabolomic prognostic signature from baseline to end of NAT. - Change in Omega-3 Index and body composition variation.

- The association between Immunophenotype of lymphocyte subpopulations and tissue-based metabolic and immune-related gene-expression signatures will be described according to the type of metabolomic profile at baseline (poor versus good) and with response to therapy (pCR versus RD).

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carmen Branni, BSc; Phone Number: +3903213732292; Email: carmen.branni@uniupo.it
• Study Contact Backup: Name: Ida Taglialatela, MD; Phone Number: +3903213732292; Email: ida.taglialatela@maggioreosp.novara.it

Study Locations

• Italy
  • Novara, Italy, 28100
    • Recruiting
    • AOU Maggiore della Carità
    • Contact: Alessandra Gennari; Email: alessandra.gennari@uniupo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• - Women (regardless of menopausal status) ≥ 18 years of age
• Pathologic confirmation of breast cancer by tumor biopsy
• Immunohistochemical assessment (as per local standards) of ER and PgR status, HER2 status;
• Stage I-III breast cancer without evidence of distant metastases
• Being candidate to standard neoadjuvant therapy
• Having available tumor tissue from breast and/or lymph node at baseline
• Ability to fill a nutritional daily diary
• Medical clearance for non-agonistic physical activity
• Written informed consent to study-specific procedures

Exclusion Criteria:

• - locally advanced or inflammatory or stage IV BC;
• tumor size < 1 cm with negative nodes (pT1a, N0);
• chronic diseases or orthopedic issues that might interfere with ability to undertake a dietary and physical activity program;
• personal history of eating disorders.
• women engaged in agonistic/vigorous sport activities, not able to be compliant to exercise schedules

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: A - treatment of physician choice; Conventional anti-cancer treatment, according to the molecular subtype and standard of care; all patients in Arm A will also receive general recommendations on lifestyle, including weight control and physical activity as indicated by WHO and EUSOMA criteria (control arm).
Experimental: B - nutritional supplementation; Conventional anti-cancer treatment, according to the molecular subtype plus nutritional supplementation. Patients will be required to take on a daily basis two main long-chain polyunsaturated fatty acids omega-3 (n-3 Lc-PUFA), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), respectively at a dose of 700mg and 240mg, through 1 softgel twice a day. Besides, patients will be provided with a source of palmitoleic acid (hexadecenoic acid) equivalent to 1000mg of pure palmitoleic acid on a daily basis, through one daily 7 ml vial.	Dietary supplement: omega-3 (n-3 Lc-PUFA), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) plus a source of palmitoleic acid (hexadecenoic acid); Nutritional supplements
Experimental: C - physical activity; Conventional anti-cancer treatment, according to the molecular subtype plus indication for supervised physical exercise	Dietary supplement: omega-3 (n-3 Lc-PUFA), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) plus a source of palmitoleic acid (hexadecenoic acid); Nutritional supplements
Experimental: D - nutritional supplementation plus physical activity; Conventional anti-cancer treatment, according to the molecular subtype plus indication for supervised exercise training plus nutritional supplementation	Dietary supplement: omega-3 (n-3 Lc-PUFA), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) plus a source of palmitoleic acid (hexadecenoic acid); Nutritional supplements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of fatty acids concentration	Plasma metabolic sample will be analyzed using a GCxGC-MS instrument for the relative and absolute quantification of small molecules in order to evaluate the impact of a lifestyle intervention including dietary supplements and physical exercise on the modulation of metabolomic signatures in eBC patients candidate to NACT.	T0: baseline, prior to cycle 1 (each cycle is 21 days); T1: end of NACT, before surgery (NACT is approximately 6 months, according to biological subtype)
Omega3 Index	Assessment of Omega-3 Index in all patients cohorts at: baseline; pre-operatative (at the end of NACT) The omega3 index will assessed by the sum of DHA and EPA in erythrocytes expressed as a percentage of total erythrocyte fatty acid.	T0: baseline, prior to cycle 1 (each cycle is 21 days); T1: end of NACT, before surgery (NACT is approximately 6 months, according to biological subtype)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined lifestyle intervention	Impact of the combined lifestyle intervention on body composition. Body composition will be assessed with a multifrequency bioelectrical impedance analysis.	T0: baseline, prior to cycle 1 (each cycle is 21 days); T1: end of NACT, before surgery (NACT is approximately 6 months, according to biological subtype)
Lymphocyte subpopulations	Assessment of the immunophenotype of lymphocyte subpopulations and their correlation with metabolomic profile and response to therapy; characterization of immune-related and metabolic-related gene-expression signatures in tumor tissue and their correlation with metabolomic profile and response to therapy. Lymphocyte subpopulation will be assessed collecting blood at 1st cycle and at the last cycle of NACT (before surgery). Gene-expression signatures will be assessed on tumor biopsy and surgery tissue.	T0: baseline, prior to cycle 1 (each cycle is 21 days); T1: end of NACT, before surgery (NACT is approximately 6 months, according to biological subtype)
Antitumor activity	evaluation of pathological Complete Response (pCR) in the different treatment arms (ypT0/Tis ypN0)	From T0 until surgery, approximately 6 months (according to biological subtype)
changes in health-related Quality of Life	Quality of Life will be assessed among all patients included in the study using patient-reported outcomes (PROs) collected using a validated and standardized questionnaire: the European Organization for Cancer Research and Treatment Quality of Life Questionnaire C30, ranging from 0 to 100. A high-scale score represents a higher response level.	T0: baseline, prior to cycle 1 (each cycle is 21 days); T1: at three months after inclusion; T2: end of NACT, before surgery (NACT is approximately 6 months, according to biological subtype)
changes in health-related Quality of Life	Quality of Life will be assessed among all patients included in the study using patient-reported outcomes (PROs) collected using a validated and standardized questionnaire: the European Organization for Cancer Research and Treatment Quality of Life Questionnaire BR45, ranging from 0 to 100. A high-scale score represents a higher response level.	T0: baseline, prior to cycle 1 (each cycle is 21 days); T1: at three months after inclusion; T2: end of NACT, before surgery (NACT is approximately 6 months, according to biological subtype)
changes in health-related Quality of Life	Quality of Life will be assessed among all patients included in the study using patient-reported outcomes (PROs) collected using a validated and standardized questionnaire: Hospital Anxiety and Depression Scale, ranging from 0 to 21. A high-scale score represents a lower response level (0-7 normal, 8-10 borderline, 11-21 abnormal).	T0: baseline, prior to cycle 1 (each cycle is 21 days); T1: at three months after inclusion; T2: end of NACT, before surgery (NACT is approximately 6 months, according to biological subtype)
Impact on treatment-related adverse events	Evaluation of safety and toxicity profiles according to the NCI-CTCAE (Common Terminology Criteria for Adverse Events) v.5.0.	Evaluation will be performed before of each cycle of NACT (each cycle is 21 days). NACT is approximately 6 months, according to biological subtype.

Collaborators and Investigators

• Sponsor: University of Eastern Piedmont
• Investigators: Study Chair: Alessandra Gennari, MD, University of Piemonte Orientale

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: April 7, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: nutritional intervention; metabolomics; treatment response
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 02UPODIMETONCO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No