Exercise Interventions for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy (BENEFIT)

A Randomized 3-arm Exercise Intervention Trial for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

The BENEFIT-Study is a randomized controlled 3-arm intervention trial investigating the currently discussed hypothesis that exercise concomitant to chemotherapy (CTx) may have a beneficial effect on cancer prognosis by boosting the anti-tumoral effect of the cytostatics or by enhancing therapy compliance. This hypothesis is based on pre-clinical and exploratory clinical trials. Breast cancer patients scheduled for neoadjuvant CTx will be randomized to either a resistance training or an aerobic training concomitant to the neoadjuvant CTx, or a waiting list control group that will get no exercise intervention during neoadjuvant CTx (i.e. usual care) but will exercise after breast surgery. The primary study endpoint is the tumor size. Further, the effects of resistance and aerobic exercise on the clinical-pathologic stage (CPS-EG) score, the pathological complete response (pCR), tolerability and compliance to CTx, physical fitness, patient reported outcomes such as fatigue, sleep problems, quality of life, depressive symptoms, anxiety and pain, as well as cognitive function, and selected biomarkers will be investigated.

A confirmation of the study hypothesis would be a strong argument for patients to engage in exercise as early as during neoadjuvant CTx. The trial will also provide evidence-based guidance for patients regarding type and timing of training.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Resistance exercise; Other: Aerobic exercise; Other: Usual care during neoadjuvant chemotherapy/Exercise after surgery

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martina E Schmidt, Dr.; Phone Number: +49 6221 42 2220; Email: m.schmidt@dkfz.de
• Study Contact Backup: Name: Karen Steindorf, Prof. Dr.; Phone Number: +49 6221 42 2351; Email: k.steindorf@dkfz.de

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • National Center for Tumor Diseases (NCT)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women ≥ 18 years of Age
• Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy
• Scheduled for neoadjuvant CTx (but not yet started)
• Confirmed hormone receptor and Her2 status
• Sufficient German language skills
• Willing to train at the exercise facilities twice per week

Exclusion Criteria:

• Any physical or mental conditions that would hamper the adherence to the training programs or the completion of the study procedures
• Engaging in systematic intense exercise training (at least 1h twice per week)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aerobic exercise	Other: Aerobic exercise; The training will take place twice weekly over the course of neoadjuvant CTx at the NCT Heidelberg or in regional qualified centers under supervision and guidance of experienced exercise therapists. The aerobic exercise will be performed on a cycle ergometer (or alternatively at a treadmill, elliptical, rowing ergometer, or combination) progressing from 60% to 70% VO2max with increasing duration. During weeks 7-18 the goal is to perform an extensive interval training.
Active Comparator: Resistance exercise	Other: Resistance exercise; The training will take place twice weekly over the course of neoadjuvant CTx at the NCT Heidelberg or in regional qualified centers under supervision and guidance of experienced exercise therapists. The progressive resistance exercise comprises 8 machine-based exercises, each performed in 3 sets, 12 repetitions at 60-80% of one repetition maximum (1-RM).
Other: Waitlist control	Other: Usual care during neoadjuvant chemotherapy/Exercise after surgery; The control group receives no exercise intervention during neoadjuvant CTx, which reflects the usual care condition. To investigate effects of different exercise timing, and to provide those patients also a potential health benefit and reduce drop-out and contamination, the control group will receive 18 weeks resistance or aerobic exercise (according to their personal preferences) after breast cancer surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor size	percentage of change from the maximal diameter of the lesion assessed before neoadjuvant chemotherapy (by mammography or sonography) to the maximal diameter of the tumor assessed after neoadjuvant chemotherapy at breast surgery	change from baseline (before start of neoadjuvant chemotherapy) to breast surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPS-EG score	The Clinical-Pathologic Stage (CPS-EG) score combines clinical tumor stage prior to neoadjuvant therapy (CS), pathological tumor stage after neoadjuvant treatment (PS), estrogen receptor status (E) and grading (G). It has been shown to be a valid prognostic factor to discriminate among patient subgroups with respect to survival after neoadjuvant CTx.	at breast surgery
pCR	The Pathological Complete Response (pCR) is defined as ypT0/is ypN0 and has been consistently demonstrated to be a good prognostic factor for long-term benefit from neoadjuvant CTx.	at breast surgery
Fatigue Assessment Questionnaire (FAQ)	Validated 20-item multidimensional self-assessment questionnaire to assess the physical, affective, and cognitive dimension of cancer-related fatigue	at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery
EORTC QLQ-C30 / BR23	Validated 30-item self-assessment questionnaire to assess quality of life aspects.	at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery
Patient Health Questionnaire for Depression and Anxiety (PHQ-4)	A validated 4-item screener for depression and anxiety.	at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery
Pittsburgh Sleep Quality Index (PSQI)	Validated questionnaire to assess sleep quality and sleep problems.	at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery
Spiroergometry (VO2max)		at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
Isometric and isokinetic muscle strength measured by ISOMED 2000		at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
Body mass index		at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
Self-developed physical activity questionnaire including type, duration, frequency and intensity of sports, cycling,and walking		Follow-up (6 months and 12 months after breast surgery)
Cognitive function - HVLT-R	Hopkins Verbal Learning Test - Revised (HVLT-R)	at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
Cognitive function - TMT	Trail Making Test	at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
Cognitive function - COWA	Controlled Oral Word Association	at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
Sleep quality	Measured with ActiGraph (accelerometry)	at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery
Sleep efficiency	Measured with ActiGraph (accelerometry)	at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery

Collaborators and Investigators

• Sponsor: German Cancer Research Center
• Collaborators: University Hospital Heidelberg

Publications and helpful links

General Publications

• Kreutz C, Muller J, Schmidt ME, Steindorf K. Comparison of subjectively and objectively assessed sleep problems in breast cancer patients starting neoadjuvant chemotherapy. Support Care Cancer. 2021 Feb;29(2):1015-1023. doi: 10.1007/s00520-020-05580-0. Epub 2020 Jun 19.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: May 6, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimate): December 21, 2016

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer; fatigue; exercise; quality of life; neoadjuvant chemotherapy; resistance training; aerobic training; tumor response
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BENEFIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO