Clinical trial NCT06497322: Exercise Intervention in Women Diagnosed With Triple-negative Breast Cancer Receiving Oncologic Treatment
Official title: Effectiveness of High-intensity Interval Training During Neoadjuvant Immunochemotherapy on Complete Remission in Patients With Triple-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Breast Cancer
Triple Negative Breast Cancer
Keywords: Exercise
Immunotherapy
Oxygen uptake
CT scan
Blood markers
Lead sponsor: University Hospital of Cologne
Sponsor class: OTHER
Collaborators: name: St. Elisabeth Krankenhaus Köln-Hohenlind
First posted: 2024-07-11
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

Brief 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.

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;

Primary outcomes:
measure: Pathological complete remission of the tumor (pCR);
timeFrame: After completion of neoadjuvant therapy and after surgery (6 months from study onset)
Secondary outcomes:
measure: Mamma- Ultrasound (the overall response rate of tumor mass);
timeFrame: Baseline (prior to any data collection or therapy administration), and every three weeks during neoadjuvant chemotherapy
measure: Progression free survival and Overall survival
timeFrame: Epidemiological data collected during the study and three years afterwards
measure: Cardiorespiratory fitness
timeFrame: At baseline (prior to any data collection or therapy administration), three months after baseline, and six months after baseline (following completion of neoadjuvant therapy)
measure: OCTA - optical coherence tomography angiography
timeFrame: At baseline (prior to any data collection or therapy administration) and after the completion of neoadjuvant therapy (most commonly 6 months)
measure: Biomarkers of immune response
timeFrame: At baseline (prior to any data collection or therapy administration) and after the completion of neoadjuvant therapy (most commonly 6 months)
measure: Quality of life, cancer-related fatigue, treatment tolerance and side-effects; physical activity behavior.
timeFrame: Baseline, and after the completion of neoadjuvant therapy (most likely 6 months after baseline)
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: University Hospital of Cologne and St. Elizabeth Hospital
state: NRW
Study officials:
affiliation: University Hospital of Cologne
name: Freerk T Baumann, PhD
role: PRINCIPAL_INVESTIGATOR
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