Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy

Breast Cancer Clinical Trial

— SPORTNATHy  

Official title:

Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06190600
• Other study ID #: SPORTNATHy
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 11, 2018
• Est. completion date: December 31, 2026

Study information

• Verified date: January 2024
• Source: The Greater Poland Cancer Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 31, 2026
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Other:
• High Intensity Interval Training (HIIT)
HIIT training twice a week throughout the chemotherapy: treadmill, elliptical, stationary bicycle and indoor rower. The intensity of physical activity will be increasing during consecutive mesocycles. Each training session will begin with a 10-min. wole-body warm-up session at 50-60% hear rate (HR) max. Mesocycle 1 - one month with 4 sets of 1 min. 45 sec. of exercise at a maximal intensity of 75% HR max. Mesocycle 2 with exercises at 80% to 90% HR max divided into 3 periods: 1/ one month, session of 5 sets 1 min. 30 sec. each; 2/ two months, sessions of 5 sets 1 min. 45 sec. each; 3/ two months, sessions of 5 sets 2 min. each. Moreover patients will be instructed to individually perform- a 45-min. aerobic training session (e.g.: walking, jogging, roller skating, swimming) once a week, in patient's own time.

Drug:
• 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).

Other:
• Standard Supportive Care
Patients will be asked to perform 150-300 min. of moderate-intensity aerobic activity or 75-150 min. of vigorous aerobic activity. Each participant will be monitored by an activity watch worn at all times by the patient.

Locations

Country	Name	City	State
Poland	Ewa Tanska	Poznan	Polska

Sponsors (1)

Lead Sponsor	Collaborator
The Greater Poland Cancer Centre

Country where clinical trial is conducted

Poland, 

References & Publications (18)

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Saarto T, Sievanen H, Kellokumpu-Lehtinen P, Nikander R, Vehmanen L, Huovinen R, Kautiainen H, Jarvenpaa S, Penttinen HM, Utriainen M, Jaaskelainen AS, Elme A, Ruohola J, Palva T, Vertio H, Rautalahti M, Fogelholm M, Luoto R, Blomqvist C. Effect of supervised and home exercise training on bone mineral density among breast cancer patients. A 12-month randomised controlled trial. Osteoporos Int. 2012 May;23(5):1601-12. doi: 10.1007/s00198-011-1761-4. Epub 2011 Sep 3. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PRO-Quality of Life	Score based on the QLQ-BR23 questionnaire which includes the following scales: body image (score range 4-16), sexual functioning (score range 2-8), systemic therapy side effects (score range 7-28), breast symptoms (score range 4-16), arm symptoms (score range 3-12), sexual enjoyment (score range 1-4), future perspectives (score range 1-4), being upset by hair loss (score range 1-4); higher score meaning worse outcome (higher level of symptomatology or lower level of functioning).	5 years
Primary	Change in tumor size	Change in tumor size	1 year
Secondary	pathological response	complete pathological response (pCR, pathologic Complete Response)	1 year
Secondary	3-yr DFS	3 years disease-free survival	3 years
Secondary	overall survival	OS - overall survival	5 years
Secondary	Left Ventricle Ejection Fraction (LVEF)	A change in LVEF >10 percentage points, to a value below 50%.	6 months
Secondary	Global Longitudinal Strain (GLS)	A change in GLS >15%.	6 months
Secondary	high-sensitivity troponin	Change above 95 percentile.	6 months
Secondary	BNP	For patients with acute onset dyspnea increase <100 pg/ml, for patients with slow increase in breathlessness increase >35 pg/ml.	6 months
Secondary	Number of steps	Daily number of steps measured throughout the intervention using an activity watch.	5 years
Secondary	Calories burned during physical activity	Measured during physical activity using an activity watch.	5 years
Secondary	Daily calories burned	Measured daily using an activity watch.	5 years
Secondary	Kilometers passed	Measured throughout the intervention using an activity watch.	5 years
Secondary	Time spent actively	Daily number of minutes spent actively measured using an activity watch.	5 years
Secondary	Length of sleep	Daily number of minutes of sleep measured using an activity watch.	5 years
Secondary	Acceptance of illness	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.	5 years
Secondary	Tumor microenvironment	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.	1 year
Secondary	Change in tumor ki67 level	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.	1 year