Clinical trial NCT06928701: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Early Breast Cancer
Neoadjuvant Treatment
Keywords: treatment response
metabolomics
nutritional intervention
Lead sponsor: University of Eastern Piedmont
Sponsor class: OTHER
First posted: 2025-04-15
Enrollment: 160
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: BASIC_SCIENCE

Brief summary: 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).

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).

Eligibility criteria: 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

Primary outcomes:
measure: Variation of fatty acids concentration
timeFrame: 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)
measure: Omega3 Index
timeFrame: 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 outcomes:
measure: Combined lifestyle intervention
timeFrame: 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)
measure: Lymphocyte subpopulations
timeFrame: 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)
measure: Antitumor activity
timeFrame: From T0 until surgery, approximately 6 months (according to biological subtype)
measure: changes in health-related Quality of Life
timeFrame: 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)
measure: changes in health-related Quality of Life
timeFrame: 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)
measure: changes in health-related Quality of Life
timeFrame: 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)
measure: Impact on treatment-related adverse events
timeFrame: Evaluation will be performed before of each cycle of NACT (each cycle is 21 days). NACT is approximately 6 months, according to biological subtype.
Other outcomes:
Locations:
city: Novara
country: Italy
facility: AOU Maggiore della Carità
Study officials:
affiliation: University of Piemonte Orientale
name: Alessandra Gennari, MD
role: STUDY_CHAIR
References: