Clinical trial NCT06727487: OvS Breast: Ovarian Suppression in Breast Cancer Interventions
Official title: OvS Breast: ENBI Project, Ovarian Suppression in Breast Cancer: Exercise, Nutrition and Behavioural Intervention Project
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Neoplasms
Keywords: Physical Exercise
Nutritional advice
Psico-oncological support
Patient Report Outcomes
Lead sponsor: Universidad Pontificia Comillas
Sponsor class: OTHER
Collaborators: name: Hospital General Universitario Gregorio Marañon
name: San Juan de Dios Foundation
First posted: 2024-12-11
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare a combined intervention based on physical exercise, nutritional control, and individualized psycho-oncological support can achieve weight control and maintain adequate body composition in premenopausal women with localized BC with ER and/or PR expression who receive aLHRH in combination with TAM or AI as part of adjuvant treatment.

The study's primary objectives are to evaluate the impact of the combined intervention on weight reduction and favorable modification of body composition in terms of reduction in body fat and increase in lean mass.

The secondary objectives aim to evaluate the impact of the combined intervention program on CRF, heart rate (HR), capillary lactate levels, upper and lower body strength, physical functionality, and patient-reported outcomes (PROs). (exercise level, asthenia, self-perception, anxiety and depression), blood count and biochemistry values that could be modified, nutritional situation, and side effects of treatments.

Detailed description: Breast cancer (BC) is the most common and incident neoplasia in women in Spain and is the third cause of cancer death after lung and colorectal cancer. In turn, BC with hormone receptor expression is the most common and corresponds to approximately 75% of BC cases.

Suppression of ovarian function combined with endocrine treatment (gonadotropin-releasing hormone analog (LHRH) associated with tamoxifen (TAM) or aromatase inhibitors (AI)) has demonstrated a benefit in terms of relapse-free survival (PFS) and overall survival (OS) in premenopausal women diagnosed with localized BC with estrogen receptor (ER) and progesterone (PR) expression. This benefit is mainly focused on patients diagnosed at younger ages (under 45 years) and those with other clinical-pathological factors that imply an exceptionally high risk of relapse.

Despite their benefits, the adverse effects of these treatments are not trivial and include significant toxicities in the cardiorespiratory, metabolic, sexual, and emotional spheres. Metabolic alterations include unfavorable changes in body composition with increases in the percentage of fat and weight that can be observed already in the first months of treatment, which in turn is directly related to an increased risk of BC relapse in these patients.

Changes in body composition with increased fat and decreased muscle mass lead to a pro-inflammatory and dysfunctional state of the immune system, which in turn has been linked to the development of cardiovascular diseases and a worse oncological prognosis.

Scientific evidence suggests that nutritional interventions combined with physical exercise and adapted to physiological needs, the baseline physical level, and the adverse effects derived from the treatments can be safe and effective in achieving adequate weight control and body composition. All of this would favor restoring the immune system's functionality and increasing patients' cardiorespiratory capacity (CRF), which could ultimately translate into a better quality of life.

However, adherence to these programs is low for many reasons, and psycho-oncological support with behavioral interventions could favor adherence to them and stimulate changes in patients' lifestyles.

Despite the evidence, there is no scientific consensus regarding the dosage of exercise and the type of nutritional intervention that should be applied to patients with BC whose treatment includes suppression of ovarian function. In this sense, these interventions should be individualized and adapted to the characteristics of each patient, taking into account all the factors that could affect adherence to these programs.

This project has been designed as a pilot study to evaluate the impact of an intervention program incorporating physical exercise and nutritional control strategies adapted to the baseline situation and level of physical fitness of each premenopausal patient with localized BC on adjuvant treatment with ovarian function suppression.

HYPOTHESIS AND OBJECTIVES: combined intervention based on physical exercise, nutritional control, and individualized psycho-oncological support can achieve weight control and maintain adequate body composition in premenopausal women with localized BC with ER and PR expression who receive aLHRH in combination with TAM or AI as part of their adjuvant treatment.

The study's primary objectives are to evaluate the impact of the combined intervention on weight reduction and favorable modification of body composition in terms of reduction of body fat and increase of lean mass.

The secondary objectives aim to evaluate the impact of the combined intervention program on CRF, heart rate (HR), capillary lactate levels, upper and lower body strength, physical functionality, patient-reported outcomes (PROs) (exercise level, asthenia, self-perception, anxiety, and depression), blood count and biochemistry values that could be modified, nutritional status and side effects of the treatments.

The exploratory objectives, on the other hand, consist of evaluating the impact of the combined intervention on the levels of pro-inflammatory substances (C-reactive protein (CRP) and TNF-alpha) and anti-inflammatory substances (adiponectin) as well as on the levels of oncostatin M, a myokine whose release increases with exercise and seems to stimulate apoptosis and interfere with exercise.

Eligibility criteria: Inclusion Criteria:

* Women who have reached the age of majority and up to 45 years of age.
* Premenopausal status is defined clinically as a patient who maintains menstruation prior to the start of chemotherapy treatment if this has taken place.
* Confirmed histological diagnosis of infiltrating breast carcinoma with expression of ER and/or RP stage I to III.
* Loco-regional treatment with surgery and radiotherapy, if any, completed.
* Adjuvant treatment with drugs that suppress ovarian function (aLHRH) is ongoing and expected to be maintained for at least 4 months at the beginning of the study.
* Functional status according to the Eastern Cooperative Oncology Group (ECOG) scale 0-1.
* Ability to understand and agree to the Informed Consent in writing.

Exclusion Criteria:

* Presence of medical contraindications to perform physical exercise.
* Presence of any of the American Thoracic Society (ATS) criteria to perform a cardiovascular capacity test.
* Presence of active neoplastic disease: metastatic breast cancer or other active tumor diseases.
* Pregnancy or breastfeeding.
* Alcohol or other drug abuse (excluding smoking).

Primary outcomes:
measure: Combined intervention evaluation on weight control
timeFrame: 1 year
measure: Combined intervention evaluation in body composition
timeFrame: 1 year
Secondary outcomes:
measure: Improve Quality of Life on Patient Report Outcomes
timeFrame: 1 year
measure: Nutritional Status follow-up
timeFrame: 1 year
measure: Psycho-oncological assessment
timeFrame: 1 year
measure: Cardiorespiratory Fitness: Evaluation of physical activity performance
timeFrame: 1 year
measure: Endurance performance: Evaluation of physical activity performance:
timeFrame: 1 year
measure: Strength: Evaluation of physical activity performance
timeFrame: 1 year
measure: Physical functionality: Evaluation of physical activity performance
timeFrame: 1 year
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Universidad Pontificia Comillas
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
Study officials:
affiliation: Universidad Pontificia Comillas
name: Julio C de la Torre, Ph.D
role: STUDY_CHAIR
affiliation: Hospital Universitario Gregorio Marañón
name: Blanca Herrero López, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Comillas Pontifical University
name: Soraya Casla Barrio, Ph.D
role: STUDY_DIRECTOR
References:
citation: Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Lang I, Gomez HL, Tondini C, Ciruelos E, Burstein HJ, Bonnefoi HR, Bellet M, Martino S, Geyer CE Jr, Goetz MP, Stearns V, Pinotti G, Puglisi F, Spazzapan S, Climent MA, Pavesi L, Ruhstaller T, Davidson NE, Coleman R, Debled M, Buchholz S, Ingle JN, Winer EP, Maibach R, Rabaglio-Poretti M, Ruepp B, Di Leo A, Coates AS, Gelber RD, Goldhirsch A, Regan MM; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med. 2018 Jul 12;379(2):122-137. doi: 10.1056/NEJMoa1803164. Epub 2018 Jun 4.
citation: Francis PA, Fleming GF, Lang I, Ciruelos EM, Bonnefoi HR, Bellet M, Bernardo A, Climent MA, Martino S, Bermejo B, Burstein HJ, Davidson NE, Geyer CE Jr, Walley BA, Ingle JN, Coleman RE, Muller B, Le Du F, Loibl S, Winer EP, Ruepp B, Loi S, Colleoni M, Coates AS, Gelber RD, Goldhirsch A, Regan MM; SOFT Investigators and the International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation). Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT. J Clin Oncol. 2023 Mar 1;41(7):1370-1375. doi: 10.1200/JCO.22.01065. Epub 2022 Dec 9.
citation: Lu YS, Wong A, Kim HJ. Ovarian Function Suppression With Luteinizing Hormone-Releasing Hormone Agonists for the Treatment of Hormone Receptor-Positive Early Breast Cancer in Premenopausal Women. Front Oncol. 2021 Sep 14;11:700722. doi: 10.3389/fonc.2021.700722. eCollection 2021.