Trial Title:
Exercise Intervention in Women Diagnosed With Triple-negative Breast Cancer Receiving Oncologic Treatment
NCT ID:
NCT06497322
Condition:
Breast Cancer
Triple Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Conditions: Keywords:
Exercise
Immunotherapy
Oxygen uptake
CT scan
Blood markers
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Prospective randomized controlled intervention (1:1 randomization). Specifically, 1
control group (usual care) and 1 intervention group (HIIT aerobic training), both
receiving neoadjuvant therapy (immunochemotherapy) by infusion, as follows; Paclitaxel
80mg/m2 q1w x12, carboplatin 1.5 AUC q1w x12, pembrolizumab 200mg q3w x4, followed by
epirubicin 90mg/ m2 q3w x 4, cyclophosphamide 600mg m2 q3w x 4, pembrolizumab 200mg q3w x
4. The intervention period (oncologic therapy + exercise intervention) is approximately 6
months (including screening phase and baseline data collection, tao), data collection
after three months (ta1), after completion of neoadjuvant therapy (~six months ta2),
during which participants will complete the exercise intervention + oncologic treatment
on site. Surgery will take place 2-3 weeks later.
Primary purpose:
Treatment
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Other
Intervention name:
Exercise intervention - High intensity interval training on a cycle-ergometer
Description:
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.
Arm group label:
Experimental group
Summary:
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.
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.
Criteria for eligibility:
Criteria:
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;
Gender:
Female
Minimum age:
18 Years
Maximum age:
85 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital of Cologne and St. Elizabeth Hospital
Address:
City:
Cologne
Zip:
50937
Country:
Germany
Contact:
Last name:
Damir Zubac, PhD
Phone:
0221 478-97185
Email:
damir.zubac@uk-koeln.de
Contact backup:
Last name:
Freerk T baumann, PhD
Email:
freerk.baumann@uk-koeln.de
Investigator:
Last name:
Freerk T Baumann, PhD
Email:
Principal Investigator
Investigator:
Last name:
Damir Zubac, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Paul Bröckelmann, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Michael Mendes Wefelnberg
Email:
Sub-Investigator
Investigator:
Last name:
Julian Puppe, MD
Email:
Sub-Investigator
Investigator:
Last name:
Susanne Brandner, MD
Email:
Principal Investigator
Start date:
September 1, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
University Hospital of Cologne
Agency class:
Other
Collaborator:
Agency:
St. Elisabeth Krankenhaus Köln-Hohenlind
Agency class:
Other
Source:
University Hospital of Cologne
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06497322
