Impact of Exercise on Quality of Life of EBC Patients on Treatment With Adjuvant AI With or Without CDK4/6 Inhibitors

Official title

Impact of EXercise on Quality of Life of Early Breast Cancer Patients on Treatment With Adjuvant Aromatase Inhibitors With or Without CDK4/6 Inhibitors. "The EXAI Study"

Overview

This is a national clinical trial (Spain), conducted in approximately 5 sites, where patients who agree to participate will be included in one of two exercise program groups: the experimental group (a combined resistance and aerobic exercise program) and the control group. The study will begin with a pilot phase involving approximately 74 patients. Approximately 37 patients in the experimental group will follow a 6-month training program consisting of exercise sessions three alternate days per week (combining resistance and aerobic exercise). Approximately 37 patients in the control group will receive standard medical care. These patients will be provided with international exercise guidelines for cancer patients. Patients will continue with their assigned physical activity intervention until the maximum number of months for the intervention, unacceptable toxicity, discontinuation of hormone therapy, or withdrawal of consent-whichever occurs first.

Detailed description

Study population:

The target population for randomization in this study includes women diagnosed with Hormone receptor (HR)+/Human epidermal growth factor receptor 2 (HER2)-negative- early-stage breast cancer (EBC) and who have already received between 10 and 18 weeks of an AI (with or without a LHRHa) before the randomization in the study. Those patients that are candidates to receive an adjuvant CDK4/6i should have initiated the treatment at least 6 weeks before the randomization in the study.

Study treatment:

Although patients should receive adjuvant ET (including an AI \[steroidal inhibitors such as exemestane or non-steroidal inhibitors such as anastrozole or letrozole\], with or without a CDK4/6i and with or without a LHRHa) to be eligible for this study, the clinical decisions concerning the optimum management strategy for a particular patient will be taken independently of and prior to any decision by the investigator to invite a patient to participate in the study and according to the approved product information, local treatment guidelines and/or routine clinical practice.

The EX-AI study has been developed to be pragmatic as it adheres to local guidelines for the use of ET in the adjuvant setting. There are no extra tests or assessments required as we allow patients management to follow the standard of care. The burden on patients is limited to completing the training program and questionnaires/scales. The diagnostic and monitoring procedures used do not introduce any risk or burden beyond those associated with routine clinical practice in Spain.

The study is mainly focused on the completion of physical activity interventions by patients and its effect on their QoL rather than the adjuvant treatment that they will be receiving.

Study duration:

The study start date is the date of the first site activation. It is estimated that the accrual will be completed in approximately 18 months. The end of study (EoS) date is the date of the last visit of the last patient (LPLV =last patient last visit), considering 6 months of the exercise program, and its potential extension for 6 additional months depending on the progress of the study and once the necessary funding for this extension has been obtained; in case it is extended, patients in both groups will be able to choose whether they would want to continue in the study for these additional 6 months follow-up. If the patients in the control group agree to continue, then they would have a passive follow-up (i.e., maintaining the same physical activity that they performed up to date). The patients in the experimental group that agree to continue would be able to choose to continue in the study through an active or passive follow-up; if they decide to continue in an active follow-up, then they would continue with the training program as previously performed; if they choose to continue in the passive follow-up on the contrary, then they would not continue with the training program as previously performed but would be encouraged to remain physically active considering international recommendations (like in the control group).The evaluation of the exploratory objectives will be independent of the EoS date.

Interventions

• Behavioral Training program
  Training program consist on physical activity sessions (combined resistance plus aerobic exercises) that will be performed 3 times per week every-other-day.

Primary outcome measures

• Effect of a training program in quality of life questionnaire (QoL)-related to endocrine therapy [Time frame: Through study treatment, and average of 12 months]

Secondary outcome measures (12)

• Change from baseline in global QoL [Time frame: Through study treatment, and average of 12 months]
• Aromatase inhibitor associated musculoskeletal syndrome (AIMSS) [Time frame: Through study treatment, and average of 12 months]
• Fatigue [Time frame: Through study treatment, and average of 12 months]
• Compliance to treatment [Time frame: Through study treatment, and average of 12 months]
• Body composition [Time frame: Through study treatment, and average of 12 months]
• Adherence to the physical activity program [Time frame: Through study treatment, and average of 12 months]
• Information on sexual relations: libido [Time frame: Through study treatment, and average of 12 months]
• Information on sexual relations: body image [Time frame: Through study treatment, and average of 12 months]
• Information on sexual relations: vaginal dryness [Time frame: Through study treatment, and average of 12 months]
• Cognitive impairment [Time frame: Through study treatment, and average of 12 months]
• The Number of Participants Who Experienced Adverse Events (AE) Related to Study Treatment [Time frame: Through study treatment, and average of 12 months]
• Tolerability to the treatment [Time frame: Through study treatment, and average of 12 months]

Eligibility criteria

Inclusion criteria

• Written informed consent document (ICD) prior to any specific study procedures, showing patience, willingness and ability to comply with the physical activity program in the experimental group, and scheduled visits and study procedures in both groups.
• Patients ≥18 years of age at signing of ICD.
• Documented histologically confirmed HR+/HER2- invasive EBC, adequately treated according to standard clinical practice and with absence of any evidence of disease (loco-regional or metastatic at distance).

HR and HER2 assessments are performed under institutional guidelines.

• HR testing should utilize an assay consistent with the most recent American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) Guidelines.
• HER2 negativity is determined as immunohistochemistry (IHC) score 0/1+ or negative by in situ hybridization (ISH) according to the recommendations of the most recent ASCO/CAP Guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
• Pre-, peri-, and post-menopausal women (as determined by the investigator and according to the institutional guidelines) that have already received between 10 and 18 weeks of an AI (with or without a LHRHa) before the randomization in the study and administered according to local guidelines.

Note: Patients that are candidate to receive an adjuvant CDK4/6i will only be eligible if the CDK4/6i was initiated at least 6 weeks before the randomization in the study and administered according to local guidelines.

• Patients must have undergone adequate (definitive) loco-regional therapy (surgery with or without radiation therapy), with or without neo-/adjuvant systemic CT.
• Patients must have an adequate organ and bone marrow function according to the standard clinical practice and institutional guidelines.
• Patients must be able and willing to fill out repeated questionnaires on QoL, pain and fatigue, as well as to adhere to the physical activity program.
• Fluent Spanish language skills for the complete comprehension of the questionnaires.
• With the consent of the investigator for participation in physical training and considering the medical history of the patient.

Exclusion criteria

• Patients have received less than 10 weeks or more than 18 weeks of an AI (with or without a LHRHa) before the randomization in the study.
• Patients that are candidate to receive an adjuvant CDK4/6i initiated the treatment less than 6 weeks before the randomization in the study.
• Patients have musculoskeletal injuries.
• Patients have known significant heart disease (myocardial infarction, unstable angina, congestive heart failure, cardiomyopathy, etc.).
• Patients with weight over 150kg.
• Patients have any type of illness or mental condition that prevents or compromises the well-being of the patient or compliance with the procedures.
• Patients have any cardiovascular contraindication to physical training by the investigator.
• Patients have been performing supervised training, either aerobic and/or resistance training (at a gym \[group or individual classes\] or in a specific sport), at least 2 days per week in the past 6 months.
• No access and/or unable to manage the website and other digital tools (i.e. applications) for training sessions.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

Spain · 5 centers

• Institut Català d'Oncología (ICO) L'Hospitalet — L'Hospitalet de Llobregat
• Hospital Universitario de Navarra — Pamplona
• Hospital Universitario Clínico San Cecilio — Granada
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Quirón Sagrado Corazón de Sevilla — Seville

Identifiers

NCT: NCT07215364 · GEICAM/2023-09 · 2025-522848-40-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗