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

NCT06497322 | Not Yet Recruiting

• 1 other identifier: No. 13-050
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Keywords

Exercise; Immunotherapy; Oxygen uptake; CT scan; Blood markers

Outcome Measures

Primary Outcomes (1)

• Pathological complete remission of the tumor (pCR);

  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 Outcomes (6)

• Mamma- Ultrasound (the overall response rate of tumor mass);

  Baseline (prior to any data collection or therapy administration), and every three weeks during neoadjuvant chemotherapy

• Progression free survival and Overall survival

  Epidemiological data collected during the study and three years afterwards

• Cardiorespiratory fitness

  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

  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

  At baseline (prior to any data collection or therapy administration) and after the completion of neoadjuvant therapy (most commonly 6 months)

Study Arms (2)

Experimental group

EXPERIMENTAL

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

Control group

NO INTERVENTION

The control group will receive the standard care during their neoadjuvant therapy (immunochemotherapy) over a 6-month period.

Interventions

Exercise intervention - High intensity interval training on a cycle-ergometer OTHER

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.

Experimental group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• University Hospital of Cologne: lead
• St. Elisabeth Krankenhaus Köln-Hohenlind: collaborator

Study Sites (1)

University Hospital of Cologne and St. Elizabeth Hospital

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Related Publications (8)

• Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.

  PMID: 32101663 RESULT

• Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Perez-Garcia J, Iwata H, Masuda N, Torregroza Otero M, Gokmen E, Loi S, Guo Z, Zhou X, Karantza V, Pan W, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022 Jul 21;387(3):217-226. doi: 10.1056/NEJMoa2202809.

  PMID: 35857659 RESULT

• Sheinboim D, Parikh S, Manich P, Markus I, Dahan S, Parikh R, Stubbs E, Cohen G, Zemser-Werner V, Bell RE, Ruiz SA, Percik R, Brenner R, Leibou S, Vaknine H, Arad G, Gerber Y, Keinan-Boker L, Shimony T, Bikovski L, Goldstein N, Constantini K, Labes S, Mordechai S, Doron H, Lonescu A, Ziv T, Nizri E, Choshen G, Eldar-Finkelman H, Tabach Y, Helman A, Ben-Eliyahu S, Erez N, Perlson E, Geiger T, Ben-Zvi D, Khaled M, Gepner Y, Levy C. An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination. Cancer Res. 2022 Nov 15;82(22):4164-4178. doi: 10.1158/0008-5472.CAN-22-0237.

  PMID: 36084256 RESULT

• Wolin KY, Yan Y, Colditz GA. Physical activity and risk of colon adenoma: a meta-analysis. Br J Cancer. 2011 Mar 1;104(5):882-5. doi: 10.1038/sj.bjc.6606045. Epub 2011 Feb 8.

  PMID: 21304525 RESULT

• Wu Y, Zhang D, Kang S. Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2013 Feb;137(3):869-82. doi: 10.1007/s10549-012-2396-7. Epub 2012 Dec 30.

  PMID: 23274845 RESULT

• Sanft T, Harrigan M, McGowan C, Cartmel B, Zupa M, Li FY, Ferrucci LM, Puklin L, Cao A, Nguyen TH, Neuhouser ML, Hershman DL, Basen-Engquist K, Jones BA, Knobf T, Chagpar AB, Silber A, Tanasijevic A, Ligibel JA, Irwin ML. Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study. J Clin Oncol. 2023 Dec 1;41(34):5285-5295. doi: 10.1200/JCO.23.00871. Epub 2023 Sep 1.

  PMID: 37656930 RESULT

• Lavin-Perez AM, Collado-Mateo D, Mayo X, Humphreys L, Liguori G, James Copeland R, Del Villar Alvarez F, Jimenez A. High-intensity exercise to improve cardiorespiratory fitness in cancer patients and survivors: A systematic review and meta-analysis. Scand J Med Sci Sports. 2021 Feb;31(2):265-294. doi: 10.1111/sms.13861. Epub 2020 Nov 5.

  PMID: 33098219 RESULT

• Gouez M, Perol O, Perol M, Caux C, Menetrier-Caux C, Villard M, Walzer T, Delrieu L, Saintigny P, Marijnen P, Pialoux V, Fervers B. Effect of acute aerobic exercise before immunotherapy and chemotherapy infusion in patients with metastatic non-small-cell lung cancer: protocol for the ERICA feasibility trial. BMJ Open. 2022 Apr 7;12(4):e056819. doi: 10.1136/bmjopen-2021-056819.

  PMID: 35393316 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms; Motor Activity

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Behavior

Study Officials

• Freerk T Baumann, PhD

  University Hospital of Cologne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Freerk T Baumann, PhD

CONTACT

0221-478-42649; freerk.baumann@uk-koeln.de

Damir Zubac, PhD

CONTACT

damir.zubac@uk-koeln.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.dr. Freerk T. Baumann

Model Details: 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.

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: July 11, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After data collection and analysis are completed.
• Access Criteria: Upon reasonable request to the study principal investigator.

Locations

DE (1)