Clinical Trial Evaluating the Efficacy and Implementation of an Early Adapted Physical Activity to Prevent and Manage Aromatase Inhibitor-induced Musculoskeletal Pain in Breast Cancer (APIS)

Official title

Randomized Clinical Trial Evaluating the Efficacy and Implementation of an Early Adapted Physical Activity to Prevent and Manage Aromatase Inhibitor-induced Musculoskeletal Pain in Breast Cancer

Overview

Aromatase inhibitors (AI) are the standard adjuvant hormone therapy for postmenopausal women with hormone-sensitive breast cancer. However, nearly half of patients experience AI-induced musculoskeletal symptoms (AIMSS), particularly pain, which compromise quality of life and treatment adherence. While adapted physical activity offers proven benefits in oncology, its specific role in preventing or managing AIMSS remains unclear. Moreover, the maintenance of physical activity during the care pathway in real-world settings is limited, highlighting the need for hybrid approaches that evaluate both clinical effectiveness and implementation. In response to these challenges, the primary study aim will be to compare the prevalence of musculoskeletal pain after six months of aromatase inhibitor therapy between patients initiating a personalized adapted physical activity program at the beginning of the care pathway and those receiving usual care. Secondary aims will be to (1) assess additional effects of the intervention on physical health, psychosocial well-being and treatment adherence, (2) explore contextual factors influencing program implementation in routine oncology care and (3) identify potential risk factors for the development of AIMSS. The APIS study is a hybrid type I effectiveness-implementation randomized controlled trial including 182 postmenopausal women with non-metastatic hormone-sensitive breast cancer. APIS will generate new evidence on the clinical and implementation effectiveness of early personalized APA (Adapted Physical Activity) in preventing AIMSS. The hybrid design will support the development of sustainable, patient-centered interventions, potentially improving quality of life, adherence to AI therapy and long-term outcomes in breast cancer survivorship. Ancillary study (Groupement Hospitalier Nord, Hospices Civils de Lyon) The humero-scapulo-thoracic region is particularly exposed to functional alterations during the course of care of patients treated for breast cancer. In addition to the loss of strength and mobility associated with surgical and medical treatment, the shoulder can also be the site of pain due to AIMSS or PMDS (Post-Mastectomy Pain Syndrome). These pains are often studied separately, depending on the treatment, but few studies offer a global vision of the functional evolution of the shoulder throughout the course of care, enabling prevention and adjustment of management. It is also relevant to assume that early APA treatment could improve functional rehabilitation in this area. The aim of this study is therefore to evaluate the impact of an APA assessment and early referral to a personalized program (APIS protocol) on shoulder functionality, depending on the time of intervention in the therapeutic pathway.

Interventions

• Behavioral Adapted Physical Activity started early
  The Adapted Physical Activity program is decided during the initial assessment. The total duration of the rehabilitation protocol is 12 weeks, with 2 one-hour sessions per week. The rehabilitation protocol chosen in this study is mixed, i.e. it combines : * Exercise training on ergocyclometer or treadmill * Flexibility and muscle-strengthening work supervised by a physiotherapist * Free work with the APA practitioner
• Behavioral Adapted Physical Activity begins at the start of hormone therapy
  Adapted Physical Activity begins at the start of hormone therapy The total duration of the rehabilitation protocol is 12 weeks, with 2 one-hour sessions per week. The rehabilitation protocol chosen in this study is mixed, i.e. it combines : * Exercise training on ergocyclometer or treadmill * Flexibility and muscle-strengthening work supervised by a physiotherapist * Free work with the APA practitioner

Primary outcome measures

• Score of most intense musculoskeletal pain [Time frame: 6 months after introduction of hormone therapy]

Secondary outcome measures (12)

• Evolution of musculoskeletal pain intensity [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Score of global pain [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Evaluation of Quality of life [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Fatigue [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Anxiety [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Cognitive complaints [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Physical condition [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Weight [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Height [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Body Mass Index (BMI) [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Waist circumference [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]
• Percentage of body fat [Time frame: From the initial phase to 6 months after the introduction of Aromatase Inhibitors.]

Eligibility criteria

Inclusion criteria

Quantitative study:

• Women aged 18 to 75
• Person with non-metastatic breast cancer
• positive for at least one hormone receptor
• Person treated with an Aromatase Inhibitor
• Person with the following treatment regimen: Surgery - radiotherapy - aromatase inhibitor hormone therapy or surgery - chemotherapy (neoadjuvant or adjuvant) +/- targeted therapy - +/- radiotherapy - aromatase inhibitor hormone therapy.
• Person affiliated to a social security scheme
• Person having signed a free and informed consent

Qualitative study:

For patients :

• Patient having given consent to participate in the APIS study
• Patient agreeing to participate in the qualitative study (box checked on the APIS informed consent form)
• Patient agreeing to the recording of the semi-directive interview

For healthcare professionals :

• Person practicing within the Saint-Étienne University Hospital and the Croix-Rousse University Hospital as a surgeon, oncologist, radiotherapist, sports medicine physician, APA instructor, physiotherapist, head nurse, care coordinator nurse, or advanced practice nurse
• Persons working with patients treated with aromatase inhibitors for non-metastatic breast cancer
• Person who has received individual information
• Person who has given consent to participate in the study
• Person agreeing to the recording of the semi-directive interview
• Person of legal age

Ancillary study :

• Eligible patient who has given consent to participate in the APIS study
• Patient agreeing to participate in the ancillary study (box checked on the APIS informed consent form)

Exclusion criteria

For all patients:

• Person deprived of liberty by judicial or administrative decision
• Person under psychiatric care (unstable pathology)
• Person of full age under legal protection (guardianship, curatorship)
• Person unable to receive sufficient information due to impaired higher functions, or insufficient command of the French language
• Person participating in another interventional research study with an exclusion period still in progress at the time of pre-inclusion
• Person with absolute contraindications to physical exercise:

• Unstable angina
• Decompensated heart failure
• Complex ventricular rhythm disorders
• Uncontrolled severe arterial hypertension
• Pulmonary arterial hypertension (> 60 mm Hg)
• Presence of large or pedunculated intracavitary thrombus
• Acute pericardial effusion
• Severe obstructive cardiomyopathy
• Tight and/or symptomatic aortic stenosis
• Recent thrombophlebitis with or without pulmonary embolism
• Diabetes with plantar perforator disease for physical activity activities involving the lower limbs
• Persons with musculoskeletal pathologies making cycling impossible

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

France · 2 centers

• Service de Gynécologie-Obstétrique, Groupement Hospitalier Nord, Hospices Civils de Lyon — Lyon
• Service de Chirurgie Gynécologie-Obstétrique,CHU Hôpital Nord — Saint-Priest-en-Jarez

Publications

• Piazzon N, Verot E, Gerard A, Baudot A, Carrouel F, Cortet M. Early adapted physical activity to prevent and manage aromatase inhibitor-induced musculoskeletal pain in breast cancer: protocol for a hybrid effectiveness-implementation randomised controlled trial (APIS). BMJ Open Sport Exerc Med. 2026 May 14;12(2):e003179. doi: 10.1136/bmjsem-2025-003179. eCollection 2026. PMID 42158292

Identifiers

NCT: NCT07295457 · 69HCL24_0748

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗