Exercise Intervention in Women Diagnosed With Triple-negative Breast Cancer Receiving Oncologic Treatment

July 4, 2024 updated by: Freerk Bauman, University Hospital of Cologne

Effectiveness of High-intensity Interval Training During Neoadjuvant Immunochemotherapy on Complete Remission in Patients With Triple-negative Breast Cancer

In this randomized, controlled, prospective, two-arm intervention study, the investigators plan to investigate the effects of high-intensity interval training in women diagnosed with triple-negative breast cancer. Breast cancer is one of the most common cancers and one of the leading causes of cancer-related deaths worldwide. Among the different subtypes, triple-negative breast cancer accounts for about 15-20% of all breast cancer cases and is characterized by a more aggressive clinical course. Recent results indicate that the percentage of patients with a pathologic complete response was 13% higher in the chemotherapy-immunotherapy group (by 64.8%) than in the placebo-chemotherapy group (51.2). High-intensity interval training has a positive effect on the immune system, suggesting that it may improve the efficacy of chemo-immunotherapy, leading to a higher rate of pathologic complete response (pCR) in patients with newly diagnosed triple-negative breast cancer. In addition to the immunomodulatory effects, this exercise model could boost microvascular perfusion, thereby improving tumor perfusion, enhancing chemo-immunotherapy and leading to better outcomes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Recent clinical trials showed promising results in patients with triple negative breast cancer (TNBC) who received four cycles of pembrolizumab (at a dose of 200 mg) every three weeks + standard chemotherapy, compared to patients who received placebo + chemotherapy alone. Importantly, the overall risk of disease progression that precluded surgery, local or distant recurrence, occurrence of a second primary cancer, or death from any cause was 37% lower with pembrolizumab chemotherapy compared to placebo chemotherapy. Exercise training is a supportive multi-effect strategy with the ability to influence multiple organ systems. There is growing epidemiologic evidence that a physically active lifestyle is associated with a lower risk of developing cancer, particularly colon and breast cancer. Recent preclinical studies suggest that exercise can control and attenuate the growth of tumor cells. Therefore, exercise could be a potential means to increase the rate of pCR in cancer patients in general. High-intensity interval training resulted in higher cardiorespiratory fitness levels, particularly in breast cancer and lung patients who exercised for at least 8 weeks, with a significant improvement (from 2.40 to 4.19 mL-min-1-kg-1) observed compared to control groups. The aim of this study is to investigate the effects of HIIT training on immune system response and pCR rates (most commonly defined as complete eradication of the tumor as a surrogate parameter for good prognosis) during neoadjuvant immunochemotherapy in women with TNBC. The working hypothesis is that HIIT training would activate the immune system and enhance the combination of neoadjuvant treatment, leading to higher rates of pCR in the aerobic group compared to the usual treatment group. Thus, this exercise model may also promote microvascular perfusion, improve tumor perfusion, and potentially lead to more favorable outcomes in neoadjuvant therapy, increasing the efficacy of systemic treatments and allowing for better therapeutic outcomes. The researchers support the idea that high-intensity aerobic exercise may at least partially challenge the large heterogeneity in response to medical treatment in women with a first diagnosis of TNBC and lead to higher response rates in the experimental group.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Germany
    • NRW
      • Cologne, NRW, Germany, 50937
        • University Hospital of Cologne and St. Elizabeth Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Freerk T Baumann, PhD
        • Sub-Investigator:
          • Damir Zubac, PhD
        • Sub-Investigator:
          • Paul Bröckelmann, MD, PhD
        • Sub-Investigator:
          • Michael Mendes Wefelnberg
        • Sub-Investigator:
          • Julian Puppe, MD
        • Principal Investigator:
          • Susanne Brandner, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Primary diagnosis of histologically verified triple-negative breast cancer (TNBC) measurable by ultrasound imaging
  • Stage of disease: T1c and nodal status N1-2 or Stage T2-4 and nodal status N0-2
  • Deemed eligible for intended treatment with Paclitaxel 80mg/m2 q1w x12, Carboplatin 1,5 AUC q1w x12, Pembrolizumab 200mg q3w x4 followed by Epirubicin 90mg/ m2 q3w x 4, Cyclophosphamid 600mg m2 q3w x 4, Pembrolizumab 200mg q3w x 4; by the treating physician
  • Treatment in curative intent with life expectancy ≥ 3 months
  • Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and 6 months after the last dose of study treatment for participants who did not.
  • Sufficient German language skills;

Exclusion Criteria:

  • History of invasive malignancy ≤2 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  • Any history of previous systemic treatment for TNBC;

  • Any diseases that do not allow sports activity, such as:

    • Clinically-manifest heart failure (NYHA III-IV);
    • Respiratory partial or global insufficiency;
    • Permanent thrombocytopenia <10,000/µl, e.g., refractory autoimmune thrombocytopenia;
    • Congenital or acquired thrombocytopathies or coagulation disorders.
    • Symptomatic CHD (clearance certificate required, stress ECG and cardiac ultrasound recommended if necessary);
  • Participation in another exercise study;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental group
All women in the experimental group receive standardized high-intensity interval training over a period of 6 months in combination with neoadjuvant therapy (immunochemotherapy). The individual training sessions are guided and monitored by qualified exercise therapists, taking into account the side effects of ongoing treatment. Each training session will last about one hour, with the effective training time being 30 minutes. Bike training begins 1 hour before neoadjuvant therapy and then at the same time of day between therapies. The TNBC patients start with 5 minutes of cycling followed by 3 × 3 - minute HIIT training sequences, constantly alternating: i) 30 s at 90% of maximal PO (70 rpm for 30 s) and ii) 30 s of light pedaling at 20% of PO). The training session will be concluded with a 5-min cool-down cycling (easy pedaling) and stretching. This protocol will be performed twice a week throughout the study.
Other: Exercise intervention - High intensity interval training on a cycle-ergometer
The experimental group starts with 5 minutes of unloaded cycling, followed by 3 × 3-minute HIIT training sequences alternating between: i) 30 seconds at 90% of maximal PO (70 rpm for 30 seconds) and ii) 30 seconds of light pedaling at 20% of PO). Recent work suggests that this high-intensity approach to aerobic exercise is feasible and safe, even during acute oncology treatment. The HIIT sequences are interspersed with two 3-minute cycling sessions at moderate intensity. The training session will be concluded with a 5-minute cool-down by cycling (light pedaling) and stretching. This protocol will be performed twice a week throughout the study, and all patients who reach an 80% adherence threshold for the exercise intervention will be included in the final analysis.
No Intervention: Control group
The control group will receive the standard care during their neoadjuvant therapy (immunochemotherapy) over a 6-month period.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathological complete remission of the tumor (pCR);
Time Frame: After completion of neoadjuvant therapy and after surgery (6 months from study onset)
The absence of residual invasive cancer of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system)
After completion of neoadjuvant therapy and after surgery (6 months from study onset)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mamma- Ultrasound (the overall response rate of tumor mass);
Time Frame: Baseline (prior to any data collection or therapy administration), and every three weeks during neoadjuvant chemotherapy
Ultrasound imaging
Baseline (prior to any data collection or therapy administration), and every three weeks during neoadjuvant chemotherapy
Progression free survival and Overall survival
Time Frame: Epidemiological data collected during the study and three years afterwards
Clinically relevant data
Epidemiological data collected during the study and three years afterwards
Cardiorespiratory fitness
Time Frame: At baseline (prior to any data collection or therapy administration), three months after baseline, and six months after baseline (following completion of neoadjuvant therapy)
Measures of oxygen uptake via CPET
At baseline (prior to any data collection or therapy administration), three months after baseline, and six months after baseline (following completion of neoadjuvant therapy)
OCTA - optical coherence tomography angiography
Time Frame: At baseline (prior to any data collection or therapy administration) and after the completion of neoadjuvant therapy (most commonly 6 months)
Measure of blood vessel compliance for the eye
At baseline (prior to any data collection or therapy administration) and after the completion of neoadjuvant therapy (most commonly 6 months)
Biomarkers of immune response
Time Frame: At baseline (prior to any data collection or therapy administration) and after the completion of neoadjuvant therapy (most commonly 6 months)
Blood sampling to measure i) Longitudinal dynamics of soluble biomarkers such as e.g. CRP (mg/dL); ii) Longitudinal dynamics of blood counts such as e.g. leukocytes (cells/uL); iii) Longitudinal dynamics of immune cell subsets measured by flow-cytometry such as e.g. activated T-cells (CD8+HLA-DR+)
At baseline (prior to any data collection or therapy administration) and after the completion of neoadjuvant therapy (most commonly 6 months)
Quality of life, cancer-related fatigue, treatment tolerance and side-effects; physical activity behavior.
Time Frame: Baseline, and after the completion of neoadjuvant therapy (most likely 6 months after baseline)
Questionnaire items (0 - 100 scale, with 0 being lower and 100 being the higher, positive outcome);
Baseline, and after the completion of neoadjuvant therapy (most likely 6 months after baseline)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital of Cologne

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
St. Elisabeth Krankenhaus Köln-Hohenlind

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Freerk T Baumann, PhD, University Hospital of Cologne

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 25, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 4, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 11, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 11, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • No. 13-050

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All patient-related data is collected in pseudonymized form. The procedure for pseudonymization will be as follows: The investigator will receive a patient identification form in his study folder. All study patients must be entered there with their full name, date of birth, study initials, and patient documentation sheet number. The patient identification list will be kept separate from the documentation records at the center. This list must be kept completely confidential and must not leave the study center. The patient identification list must be archived for 10 years after the end of the study and then destroyed. Data processing and data management is carried out by the University Hospital Cologne. It stores all changes to the data in an audit trail and has a study-specific customizable user and role concept. The database is integrated into a general IT infrastructure and security concept with firewall and backup system.

IPD Sharing Time Frame

After data collection and analysis are completed.

IPD Sharing Access Criteria

Upon reasonable request to the study principal investigator.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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