Improving Response to Chemotherapy by Adding Physical Exercise in the Neoadjuvant Setting of Breast Cancer Patients

Not Applicable

Recruiting

• Conditions: Breast Cancer
• Interventions: Behavioral: Combined Aerobic and Resistance Exercise

• Registration Number: NCT05976815
• Lead Sponsor: University Institute of Maia

Brief Summary

One of the recommended treatments for breast cancer is neoadjuvant chemotherapy (NCT), however, only 20% of the patients subject to this therapy present pathologic complete response (pCR). If exercise-induced tumour size reductions observed in preclinical studies translates to humans, physical training could emerge as a way of increasing rates of pCR to NCT, which would be a valuable clinical achievement. The present randomized controlled trial primary aim is to assess the impact of a physical exercise intervention the NCT efficacy. Following a parallel-arm design, 86 women with primary BC will be allocated 1:1 to a NCT + exercise (experimental) or NCT alone (control) group. The primary outcome is the rate of pCR in each group. Secondary outcomes include treatment tolerability and compliance, tumour infiltrating lymphocytes, ki67, immune, inflammatory, matricellular and myogenic markers, physical fitness, accelerometry, quality of life and body composition.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-06-06
• Study First Submitted QC: 2023-07-27
• Study Start: 2023-07-31
• Study First Posted: 2023-08-04
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Primary Completion: 2026-08-01
• Study Completion: 2026-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 86

Inclusion Criteria

1. being female gender;
2. age equals or greater than 18 years old;
3. having a newly diagnosed histologically confirmed breast carcinoma IA-IIIC;
4. planned to receive neoadjuvant chemotherapy with anthracyclines or taxanes, that might be associated to anti-HER2 drugs;
5. being followed by the oncology department of the CHVNG/E;
6. medical oncologists consents the practice of physical exercise;
7. the patient is capable of providing written informed consent;
8. the participant accepts to be allocated to the control or experimental group, according to the randomization.

Exclusion Criteria

1. previous cancer diagnostic;
2. evidence of synchronous oncologic disease;
3. physical or psychiatric contraindication to the practice of physical exercise.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Group	Combined Aerobic and Resistance Exercise	The experimental group will receive neoadjuvant chemotherapy (standard of care) in conjunction with an exercise intervention. The exercise intervention will be implemented concurrently for the full duration of the neoadjuvant chemotherapy treatment.

Primary Outcome Measures

Name	Time	Method
Pathologic Complete Response	Post-intervention / Post-treatment. After neoadjuvant chemotherapy, and after surgery. Up to 33 weeks post-baseline.	Pathological response as the primary outcome will be assessed by a blinded pathologist from the tumour surgical specimens after the breast surgery (post-intervention) and will be defined as complete, partial or no response. Besides pathological complete response (defined as ypT0/ypN0), groups will be compared as those with response (complete or partial) versus those with no response. The residual cancer burden which quantifies residual disease after NAC (post-intervention) will also be assessed.

Secondary Outcome Measures

Name	Time	Method
Percentage of Tumor Infiltrating Lymphocytes	At baseline (week 0) and post-intervention (after an average of 30 weeks from study enrolment).	Assessed at Histology Slides. Intratumoral and stromal infiltrating lymphocyte (TIL) population will be assessed in tumour biopsies (at baseline) and surgical resection specimens collected from the post-neoadjuvant chemotherapy surgery (post-intervention). This will be used to compute intratumoral and stromal TIL's score, recorded as the percentage of TIL's on the analysed area. Only stromal TIL ́s will be quantified in patients with complete pathological response.
Plasma Irisin Levels	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The enzyme-linked immunosorbent assay method will be used to identify the concentration of the hormone Irisin on plasma.
Plasma Decorin Levels	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The enzyme-linked immunosorbent assay method will be used to identify the concentration of the protein Decorin on plasma.
Plasma Oncostatin M Levels	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The enzyme-linked immunosorbent assay method will be used to identify the concentration of the cytokine Oncostatin-M on plasma.
Chemotherapy Relative Dose Intensity	From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.	Chemotherapy relative dose intensity will be calculated by the following formula: (Delivered dose intensity / Standard dose intensity) x 100%, where Delivered dose intensity = (Delivered total dose, in mg/m2)/(actual time to complete chemotherapy with imputation for missed cycles, in days) and Standard Dose Intensity = (Standard total dose, in mg/m2)/(standard time to complete chemotherapy, in days).
Percentage of Natural Killer T Cells on Peripheral Blood	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Flow cytometry will be the method used to assess the number of CD3+CD56+ (natural killer T cells) on peripheral blood lymphocytes.
Plasma SPARC levels	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The enzyme-linked immunosorbent assay method will be used to identify the concentration of the protein SPARC on plasma.
Maximal Isometric Quadriceps Strength	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The maximal force (in kilograms) the participant is able to produce in an isometric strength test for the quadriceps muscle will be recorded using a load cell. Additionally, the time to maximal strength (in seconds) will also be recorded.
Number of Chemotherapy Dose Reductions	From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.	Number of patients that had to reduce the dose of chemotherapy from the dose of chemotherapy initially prescribed (standard dose intensity).
Number of Chemotherapy Early Discontinuations	From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.	Number of patients that had to interrupt chemotherapy before the standard dose had been administrated.
Treatment Tolerance - clinically assessed.	From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.	Number of participants with clinically assessed treatment-related adverse events. Will be assessed according to the Common Terminology Criteria for Adverse Events v5.0. The scale uses a minimal value of 1 and a maximal value of 5 to grade each adverse event, with higher scores representing worse outcomes.
Treatment Tolerance - patient reported.	From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.	Number of participants with patient-reported adverse events. Will be assessed using the Patient reported outcomes version of the Common Terminology Criteria for Adverse Events v1.0 questionnaire. The scale uses a minimal rating 0 and a maximal rating of 4 to grade each adverse event, with higher scores representing worse outcomes.
Number of Chemotherapy Delays	From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.	Number of patients that had to delay a cycle of chemotherapy, in comparison to what had initially been prescribed (standard dose intensity).
Percentage of Tumor Ki67	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Assessed at Histology Slides. Ki67 will be assessed in tumour biopsies (at baseline) and surgical resection specimens collected from the post-neoadjuvant chemotherapy surgery (post-intervention).
Percentage of T Helper Cells on Peripheral Blood	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Flow cytometry will be the method used to assess the number of CD3+CD4+ (T helper cells) on peripheral blood lymphocytes.
Distance traveled in the 10 meter-incremental shuttle walk test	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	As an indicator of cardiorespiratory fitness, the number of meters that the participant is able to walk/run in the 10 meter-incremental shuttle walk test will be assessed.
Percentage of Cytotoxic T Cells on Peripheral Blood	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Flow cytometry will be the method used to assess the number of CD3+CD8+ (cytotoxic T cells) on peripheral blood lymphocytes.
Health-Related Quality of Life	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The questionnaires European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (version 1.0) and the Breast 23 Questionnaire (version 1.0) will be implemented to assess cancer-related quality of life. The final scores will range from 0 to 100, with higher scores on the functional scales representing a high level of functioning and higher scores on the symptom scales implying a stronger symptom burden.
Plasma TNF-alpha levels	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The enzyme-linked immunosorbent assay method will be used to identify the concentration of the cytokine TNF-alpha on plasma.
Plasma IFN-gamma levels	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The enzyme-linked immunosorbent assay method will be used to identify the concentration of the cytokine IFN-gamma on plasma.
Maximal METS reached during a cardiopulmonary exercise test	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The participant will be subjected to a maximal incremental conventional cardiopulmonary exercise test on a treadmill. The maximal intensity the participant is able to attain in this assessment will be recorded in METS.
Weekly time time spent in light, moderate and vigorous physical activities and sedentary behaviours.	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Assessed by accelerometry over a period of seven days, the time (in minutes) that the participants spend in light, moderate and vigorous physical activity will be recorded. Additionally, the time (in minutes) spent in sedentary behaviours will also be recorded.
Total Body Skeletal Muscle Mass	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Using bioimpedance, the participants' total body skeletal muscle mass, in kilograms, will be assessed.
Number of repetitions performed in the 30 second sit-to-stand test	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The 30 second sit-to-stand test will be used to assess lower limb dynamic muscular strength. The maximal number of repetitions the participant is able to perform in the 30 second sit-to-stand test will be recorded.
Maximal Isometric Handgrip Strength	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	The maximal force (in kilograms) the participant is able to produce in an isometric handgrip test will be recorded, using a hand dynamometer.
Body Mass Index	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Using weight and height, these parameters will be combined to report BMI in kg/m\^2.
Total Body Weight	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Using bioimpedance, the participants' total body weight, in kilograms, will be assessed with the lightest clothes possible.
Total Body Fat	At baseline (week 0) and post-intervention (after an average of 30 weeks post study enrolment).	Using bioimpedance, the participants' total body fat, in kilograms, will be assessed.

Trial Locations

Locations (1)

Centro Hospitalar Vila Nova Gaia e Espinho; 🇵🇹 Gaia, Porto, Portugal