PhActHealth - Physical Activity and Healthy Aging: Fighting Low Grade Chronic Inflammation to Put Out the Cardio-oncologic Risk
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 126
- 试验地点
- 2
- 主要终点
- Exercise capacity
研究概览
简要总结
PhActHealth is a multicenter randomized controlled trial enrolling women with newly diagnosed luminal B or triple-negative breast cancer (BC) who are candidates for neoadjuvant therapy. The study aims to investigate the effects of a preoperative, unsupervised exercise training program on exercise capacity, as well as on immune response, autonomic nervous system (ANS) regulation, cardiovascular health, and tumor aggressiveness prior to surgical removal.
Participants are randomly assigned to either an intervention group or a control group. All patients receive lifestyle counseling, while those in the intervention group additionally follow a personalized aerobic and resistance exercise program throughout the neoadjuvant treatment period before surgery.
The primary outcome is the improvement in exercise capacity. The secondary outcomes are tumor-specific and systemic responses to the intervention, evaluated by analyzing molecular, metabolic, and inflammatory markers, as well as clinical and functional parameters.
详细描述
BC is strongly affected by systemic inflammation and immune alterations. Exercise has been demonstrated improving cardiometabolic health and reducing inflammatory markers in patients with oncology diseases. However, its role in the pre-operative setting, during neoadjuvant therapy, still remains poorly defined. The PhActHealth study investigates whether a structured pre-operative exercise program can improve functional capacity and modulate tumor and systemic biological markers in breast cancer patients, before surgery, and improve survival and quality of life, after surgery.
The PhActHealth study aims to comprehensively investigate the impact of a pre-operative, remotely monitored exercise training program in patients with BC, with a dual focus: (i) Improving exercise capacity; (ii) Exploring the potential modulation of biomarkers involved in tumor progression, systemic inflammation, and immune response by integrating functional assessments, biological analyses, and patient-reported outcomes.
Women with operable BC who are candidates for neoadjuvant therapy are enrolled after confirmation of eligibility criteria, and randomly assigned to either an intervention arm (IA) or a control arm (CA).
The intervention begins with the initiation of systemic therapy and continues until the planned date of surgery; then, two follow-ups are performed. At baseline, patients enrolled in both study arms receive lifestyle counseling, with specific recommendations for maintaining an active lifestyle based on the currently available international guidelines. In addition to lifestyle counseling, participants enrolled in the IA receive a personalized pre-habilitation exercise training program - which is undertaken autonomously and remotely monitored - until one week before surgery. Then, all participants undergo the planned surgical treatment, followed according to routine clinical practice, during which two follow-ups are scheduled.
The primary outcome is peak exercise capacity while secondary outcomes are tumor response and proliferation, immune and angiogenesis markers in tumor tissue, systemic inflammatory and metabolic biomarkers, body composition, autonomic function, and quality of life, overall and disease-free survival, as well as other functional and psychosocial parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •being a patient with first diagnosis of primary BC;
- •luminal BC tumor subtype B defined as positive for estrogen and/or progesterone receptor expression, HER2 negative and high Ki-67; or triple Negative BC tumor subtype defined as negative for estrogen and/or progesterone receptor expression, HER2 negative, defined by the Pathology and Medical Oncology units as defined by the ESMO Guidelines Committee (referred to the American Society of Clinical Oncology/College of American Pathologists guidelines for assessment of hormone receptor (HR) status (i.e. ER and 4 PgR)25 and HER2 status, and by the International Ki-67 in Breast Cancer Working Group for Ki-67);
- •candidate for chemotherapy/immunotherapy neoadjuvant treatment;
- •signed informed consent for study participation;
- •declared being not engaged in any competitive or recreational physical activity.
排除标准
- •therapeutic modifications during the intervention period;
- •presence of chronic conditions (such as autoimmune diseases, neurodegenerative diseases, psychiatric disorders/cognitive disabilities, chronic obstructive pulmonary disease);
- •presence of any condition that significantly impairs the ability to perform exercise;
- •pregnancy/lactation/intention to initiate pregnancy;
- •prior chemotherapy or immunotherapy within the past three years;
- •high baseline physical activity level (i.e. performing exercise at a dose of 600 MET minutes a week or greater, according to the score of the International Physical Activity Questionnaire [IPAQ]).
研究组 & 干预措施
Personalized pre-habilitation exercise training program and lifestyle counseling
Participants receive specific recommendations for maintaining an active lifestyle, with additional guidance on nutritional habits, stress management, substance use, alcohol consumption, smoking, and sleep.
Furthermore, participants are asked to wear a wrist-worn wearable device for the entire duration of the intervention in order to monitor their adherence to the intervention program: a 16-week personalized pre-habilitation exercise training, that includes a combination of aerobic endurance exercises, aimed at enhancing exercise capacity, and muscle-strengthening exercises, aimed at increasing muscle mass and strength.
干预措施: Pre-habilitation exercise program (Behavioral)
Lifestyle counseling
Participants receive specific recommendations for maintaining an active lifestyle, with additional guidance on nutritional habits, stress management, substance use, alcohol consumption, smoking, and sleep.
Furthermore, participants are asked to wear a wrist-worn wearable device for the entire duration of the intervention in order to track physical activity habits.
结局指标
主要结局
Exercise capacity
时间窗: Baseline and 6 months
Change in metabolic equivalents of task (METs) at peak exercise intensity, measured during a maximal exercise stress test.
次要结局
- Pathologic Complete Response (pCR)(At surgery, following completion of neoadjuvant treatment)
- Residual Cancer Burden (RCB)(At surgery, following completion of neoadjuvant treatment)
- Stromal Tumor-Infiltrating Lymphocytes (sTILs)(Baseline diagnostic biopsy and surgery)
- Tumor Angiogenesis(Baseline diagnostic biopsy and surgery)
- Tumor tissue Insulin-like growth factor 1 (IGF-1) expression(Baseline diagnostic biopsy and surgery)
- IGF-1 receptor expression (IGF-1R)(Baseline diagnostic biopsy and surgery)
- Liver function markers(Baseline and 6 months)
- Ki-67 expression(Baseline diagnostic biopsy and surgery)
- Lipid Profile(Baseline and 6 months)
- Blood glucose(Baseline and 6 months)
- Glycated hemoglobin (HbA1c)(Baseline and 6 months)
- Insulin(Baseline and 6 months)
- C-reactive protein (CRP)(Baseline and 6 months)
- High-sensitivity C-reactive protein (hs-CRP)(Baseline and 6 months)
- Interleukin-6 (IL-6)(Baseline and 6 months)
- Neutrophil-to-lymphocyte ratio (N/L)(Baseline and 6 months)
- Platelet-to-lymphocyte ratio (P/L)(Baseline and 6 months)
- Thyroid Function(Baseline and 6 months)
- Epigenetic markers(Baseline and post-intervention/pre-surgery)
研究者
Elia Mario Biganzoli
Full Professor of Medical Statistics
University of Milan