Clinical trial NCT06190600: Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy
Official title: Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer
physical activity
neoadjuvant chemotherapy
cardiooncology
Lead sponsor: The Greater Poland Cancer Centre
Sponsor class: OTHER
First posted: 2024-01-05
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized into two groups. Patients which are set to receive neoadjuvant chemotherapy will be selected. 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).

The group in which additional intervention IPA will be ordered, in means of supervised high intensity interval training twice a week. During the course of chemotherapy, the intensity of physical activity will be increasing. Moreover, throughout the entire therapy time, there will be introduced a 45-minute aerobic training session (e.g.: walk, jogging, roller skates, swimming) ones a week. In the control group patients will be asked to independently continue their regular physical activity same as prior to the oncologic treatment.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in tumor size
timeFrame: 1 year
Secondary outcomes:
measure: pathological response
timeFrame: 1 year
measure: 3-yr DFS
timeFrame: 3 years
measure: overall survival
timeFrame: 5 years
measure: Left Ventricle Ejection Fraction (LVEF)
timeFrame: 6 months
measure: Global Longitudinal Strain (GLS)
timeFrame: 6 months
measure: high-sensitivity troponin
timeFrame: 6 months
measure: BNP
timeFrame: 6 months
measure: Number of steps
timeFrame: 5 years
measure: Calories burned during physical activity
timeFrame: 5 years
measure: Daily calories burned
timeFrame: 5 years
measure: Kilometers passed
timeFrame: 5 years
measure: Time spent actively
timeFrame: 5 years
measure: Length of sleep
timeFrame: 5 years
measure: Acceptance of illness
timeFrame: 5 years
measure: Tumor microenvironment
timeFrame: 1 year
measure: Change in tumor ki67 level
timeFrame: 1 year
Other outcomes:
measure: PRO-Quality of Life
timeFrame: 5 years
Locations:
city: Poznań
country: Poland
facility: Ewa Tanska
state: Polska
Study officials:
affiliation: Wielkopolskie Centrum Onkologii
name: Maria Litwiniuk, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Wielkopolskie Centrum Onkologii
name: Joanna Kufel-Grabowska, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wielkopolskie Centrum Onkologii
name: Maciej Górecki, PT, PhD
role: PRINCIPAL_INVESTIGATOR
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