Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy
- Conditions
- Breast Cancer
- Interventions
- Other: High Intensity Interval Training (HIIT)Other: Standard Supportive CareDrug: neoadjuvant treatment (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab)
- Registration Number
- NCT06190600
- Lead Sponsor
- The Greater Poland Cancer Centre
- Brief Summary
The main goal of this study is to assess the impact of supervised intense physical activity (IPA) on outcomes of neoadjuvant chemotherapy in young women with breast cancer (YWBC). In this project standard neoadjuvant chemotherapy will be used concordant with summary of product characteristics (SPC). However during treatment (including days of chemotherapy application) an additional modifier of therapy will be carried out in the form of intense physical activity. This strategy is not recognized in SPC. This project aims to improve the results of breast cancer treatment in young women. According to available data, nowadays this subset of breast cancer patients has worse therapy results in comparison to older women. This is partially because of the different tumor characteristics; young women are more likely to present with human epithelial growth factor receptor 2 (HER2) receptor overexpression or with triple negative breast cancer. In the treatment of YWBC, preoperative chemotherapy is most often the first step. This enables the opportunity to assess the effectiveness of additional interventions in a mode it was never tested before. It is believed that physical activity improves the results of breast cancer treatment, however there are only few reports describing its benefit and role in terms of preoperative chemotherapy.
In the current project, the investigators planned to introduce supervised increased physical activity concurrently with neoadjuvant treatment in YWBC at early stage of disease. The main goal of the study is to assess the effect of physical activity on preoperative chemotherapy outcomes. The change of tumor size after neoadjuvant chemotherapy, as well as the impact on Quality of Life (QoL) and Patients' Reported Outcome (PRO) in described above treatment modality. Secondary endpoints are the following: the pathologic Complete Response (pCR), disease free survival after 3 years (3-yr DFS), overall survival (OS), cardiotoxicity of treatment, the effect of physical activity on tumor microenvironment and Ki67 as well as the impact of increased physical activity on further patients' lifestyle changes.
- Detailed Description
The main goal of this study is to assess the impact of supervised intense physical activity (IPA) on outcomes of neoadjuvant chemotherapy in young women with breast cancer (YWBC). In this project standard neoadjuvant chemotherapy will be used concordant with summary of product characteristics (SPC). However during treatment (including days of chemotherapy application) an additional modifier of therapy will be carried out in the form of intense physical activity. This strategy is not recognized in SPC. This project aims to improve the results of breast cancer treatment in young women. According to available data, nowadays this subset of breast cancer patients has worse therapy results in comparison to older women. This is partially because of the different tumor characteristics; young women are more likely to present with human epithelial growth factor receptor 2 (HER2) receptor overexpression or with triple negative breast cancer. In the treatment of YWBC preoperative chemotherapy is most often the first step. This enables the opportunity to assess the effectiveness of additional interventions in a mode it was never tested before. It is believed that physical activity improves the results of breast cancer treatment, however there are only few reports describing its benefit and role in terms of preoperative chemotherapy.
In the current project the investigators planned to introduce supervised increased physical activity concurrently with neoadjuvant treatment in YWBC at early stage of disease. The main goal of the study is to assess the effect of physical activity on preoperative chemotherapy outcomes. The change of tumor size after neoadjuvant chemotherapy, as well as the impact on Quality of Life (QoL) and Patients' Reported Outcome (PRO) in described above treatment modality. Secondary endpoints are the following: the pathologic Complete Response (pCR), disease free survival after 3 years (3-yr DFS), overall survival (OS), cardiotoxicity of treatment, the effect of physical activity on tumor microenvironment and Ki67 as well as the impact of increased physical activity on further patients' lifestyle changes. Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) 0-1 who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney, and bone marrow function as well as heart ejection fraction ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).
After receiving patients' agreement and signing informed consent form, the patient will undergo testing by a multidisciplinary panel of physicians. A cardiological assessment will be completed along with spiroergometry, bone density and anthropometric measurements. The patient will be asked to complete surveys assessing their QoL together with reporting their previous activity level and everyday functioning. Patients will be randomized into two groups - the comparator group undergoing chemotherapy and the intervention group in which additional intervention IPA will be ordered, in means of supervised high intensity interval training twice a week. Modalities of exercise will include: treadmill, elliptical, stationary bicycle and indoor rower. During the course of chemotherapy, the intensity of physical activity will be increasing. Moreover, throughout the entire therapy time, a 45-minute aerobic training session (e.g.: walk, jogging, roller skates, swimming) will be introduced once a week. In the control group, patients will be asked to independently perform their physical activity at an intensity and volume specified in general guidelines: 150-300 min. of moderate-intensity aerobic activity or 75-150 min. of vigorous aerobic activity. Each participant will be monitored at all times by the use of a standard biologic activity recording device.
After the administration of anthracycline, the following procedures will be done: tumor/tumor bed core needle biopsy, mammography, breast ultrasound and cardiological assessment. Following the completion of chemotherapy all testing will be repeated with the exception of bone density measurement and core biopsy. These tests will be repeated one year after surgery. In addition, patients will be assessed for their immune status before and after chemotherapy, as well as one year of observation. When tissue material is available an assessment of the composition of inflammatory infiltrate will be performed using immunohistochemical stainings for immune cell markers. The investigators also planned to preserve material taken from the primary tumor and possible metastasis for molecular analysis (next generation sequencing (NGS), microarrays). The observation will be carried out for 10 years with own resources.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 40
- women between 18 and 40 years of age,
- with a known breast cancer, triple - negative or HER2 positive when the tumor size is ≥ 2cm and / or when cancer metastases to axillary lymph nodes or with luminal cancer at tumor size> 3 cm are present,
- qualified for preoperative chemotherapy,
- ECOG 0-1,
- correct left ventricular ejection fraction of at least 50%
- correct results of laboratory tests for bone marrow, liver and kidney function (leukocytes ≥ 3 x 109 / l, neutrocytes ≥ 1.5 x 109 / l, hemoglobin ≥ 9 mg / dl [5.59 mmol / l], platelets ≥ 100 x 109 / l, AST / ALT ≤ 3 x ULN, bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 ULN).
- diagnosis with cancer other than breast cancer in the last 5 years, except in situ melanoma, in situ cervical cancer, basal cell and squamous cell carcinoma.
- other contraindications for planned systemic treatment: doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab.
- Pregnant and breastfeeding patients.
- Patients infected with HIV, HCV, HBV, after organ transplantation or suffering from an autoimmune disease requiring immunosuppressive treatment. If there are diseases of the musculoskeletal system or other, according to the doctor, preventing the patient from participating in the study or threatening her life and health if the planned intervention is used, the patient should not be included in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Neoadjuvant chemotherapy with Standard Supportive Care Standard Supportive Care Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) scale 0-1, who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney and bone marrow function as well as heart ejection fraction of ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC). High Intensity Interval Training (HIIT) neoadjuvant treatment (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab) The group in which, concurrently with chemotherapy,IPA will be ordered, by means of supervised high intensity interval training twice a week. During the course of chemotherapy, the intensity of physical activity will be increasing. Neoadjuvant chemotherapy with Standard Supportive Care neoadjuvant treatment (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab) Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) scale 0-1, who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney and bone marrow function as well as heart ejection fraction of ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC). High Intensity Interval Training (HIIT) High Intensity Interval Training (HIIT) The group in which, concurrently with chemotherapy,IPA will be ordered, by means of supervised high intensity interval training twice a week. During the course of chemotherapy, the intensity of physical activity will be increasing.
- Primary Outcome Measures
Name Time Method Change in tumor size 1 year Change in tumor size
- Secondary Outcome Measures
Name Time Method Global Longitudinal Strain (GLS) 6 months A change in GLS \>15%.
Left Ventricle Ejection Fraction (LVEF) 6 months A change in LVEF \>10 percentage points, to a value below 50%.
pathological response 1 year complete pathological response (pCR, pathologic Complete Response)
3-yr DFS 3 years 3 years disease-free survival
overall survival 5 years OS - overall survival
high-sensitivity troponin 6 months Change above 95 percentile.
Number of steps 5 years Daily number of steps measured throughout the intervention using an activity watch.
Kilometers passed 5 years Measured throughout the intervention using an activity watch.
Calories burned during physical activity 5 years Measured during physical activity using an activity watch.
BNP 6 months For patients with acute onset dyspnea increase \<100 pg/ml, for patients with slow increase in breathlessness increase \>35 pg/ml.
Daily calories burned 5 years Measured daily using an activity watch.
Time spent actively 5 years Daily number of minutes spent actively measured using an activity watch.
Change in tumor ki67 level 1 year Ki67 will be assessed based on immunohistochemical staining of paraffine section of a tumor. Ki67 index will be measured as a number of ki67-positive cells over the total number of invasive cells, and will be expressed as a percentage.
Length of sleep 5 years Daily number of minutes of sleep measured using an activity watch.
Acceptance of illness 5 years Score based on Acceptance of Illness Scale, a single scale with range of points 8-40, with a higher score meaning better acceptance of one's medical condition.
Tumor microenvironment 1 year Assessment of the percentage of immune cells infiltrating the tumor based on immunohistochemical staining of paraffin sections of a tumor. Staining will include the following markers: CD45, CD8, CD4 to assess absolute inflammatory cells, cytotoxic T cells, and helper T cells. The infiltrating cells will be measured as an area occupied by inflammatory cells over total area, and will be expressed as a percentage.
Trial Locations
- Locations (1)
Ewa Tanska
🇵🇱Poznań, Polska, Poland