Progressive Resistance Training in Head and Neck Cancer Patients During Concomitant Chemoradiotherapy

Progressive Resistance Training in Head and Neck Cancer Patients During Concomitant Chemoradiotherapy - The DAHANCA 31 Study

72 patients with head and neck cancer, undergoing primary treatment with radiation therapy and concomitant weekly cisplatin, will be recruited to this multicentre trial.

Randomized 1:1 to either 12-week progressive resistance training (PRT) program or control arm, starting together with concomitant chemoradiotherapy (CCRT) Stratified by centre, gender, p16-status and body mass index (BMI) below or above 30.

Primary endpoint is difference in change in lean body mass (LBM) between the groups and the endpoint is reduction of LBM loss in intervention arm by 25% compared to control.

Secondary endpoints include side-effects to treatment, change in body composition, physical function and strength, and compliance to PRT. Questionnaires on QoL, diet, voluntary exercise and work affiliation will also be registered.

Blood samples for explorative analyses will be drawn and optional muscle biopsies drawn for proteomics analyses and histological analyses.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Neoplasms; Weight Loss
• Intervention / Treatment: Behavioral: Progressive Resistance Training; Behavioral: physical activity; Behavioral: Diet diary

Detailed Description

The PRT program will start about the onset of radiotherapy. The program consists of 7 exercises in training machines and involves the major muscle groups of the body.

The program has previously been found to successfully restore the loss of lean body mass (LBM) in head and neck cancer patients post-treatment. A group based approach will be used to facilitate a social and motivating training environment for the patients. A pilot study (NCT02068950) showed feasibility of PRT during CCRT.

In addition to baseline data (height, tumor stage, performance status, etc), the following parameters will be registered: Weight, patient reported side effects, as well as a questionnaire on amount of physical activity and food intake.

Physical function and strength will be tested at baseline, after the course of chemoradiotherapy and at the end of the 12-week PRT programme, and at 6 and 12 months follow-up. DXA scans for body composition will be performed using a Lunar iDXA (GE Healthcare).

Blood samples will be drawn at regular intervals during the 12 weeks and at follow-up.

Patient reported quality of life (EORTC Quality of Life Questionnaire (QLQ)-C30 and QLQ-H&N35) will also be registered.

Muscle biopsies will be taken three times: at baseline, after treatment and after 12-weeks PRT.

Study duration is expected to be 18 months and an additional 12 months for follow-up.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Department of Oncology, Copenhagen University Hospital, Herlev

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with biopsy verified head and neck squamous cell carcinoma referred for primary curatively intended treatment.

• Candidates for concomitant chemoradiotherapy (2Gyx33-34; 6F/W; weekly cisplatin 40mg/m2, max. 70 mg/weekly) according to Danish Head and Neck Cancer Group (DAHANCA) guidelines (T1-4, N1-3, M0)

  • Performance status 0-1
  • At least 18 years of age.

Exclusion Criteria:

• BMI below 20.5
• diabetes
• corticosteroid treatment for other diseases
• Tonsillectomy within the last week before inclusion.
• hemoglobin below 6 mmol/l
• leucocytes below 2.5 x 10^9 /l
• thrombocytes below 50 x 10^9 /l
• comorbidities, social, familial or geographical conditions, that could compromise attendance or results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Progressive Resistance Training; 12 weeks progressive resistance training (PRT) during and after concomitant chemoradiotherapy. Also optional/voluntary physical activity performed on their own is registered, as well as diet diary.	Behavioral: Progressive Resistance Training; 12 weeks supervised resistance training program. Details of the program: 12 weeks, 3 sessions per week, 7 exercises in training machines (leg press, leg curl, hamstring curl, chest press, lateral pull down, sit-ups and back extensions). In general 2-3 sets of 8-15 repetitions will be performed following a progression plan starting with more repetitions at lower intensity progressing to fewer repetitions at higher intensity during the 12-week period (American College of Sports Medicine Position Stand); Behavioral: physical activity; Weekly diary of performed physical activity using the Physical Activity Score (PAS) during the 12-weeks intervention; Other Names: Diary of performed physical activity; Behavioral: Diet diary; Weekly diet diary during the 12-weeks intervention
Active Comparator: Control; Control arm. Optional/voluntary physical activity performed on their own is registered, as well as diet diary.	Behavioral: physical activity; Weekly diary of performed physical activity using the Physical Activity Score (PAS) during the 12-weeks intervention; Other Names: Diary of performed physical activity; Behavioral: Diet diary; Weekly diet diary during the 12-weeks intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LBM (lean body mass)	change in kilograms	at 12-weeks post PRT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LBM (lean body mass)	change in kilograms	at 6 weeks, and 6 and 12 months post RT
Fat mass	change in kilograms	at 6 and 12 weeks, and 6 and 12 months post RT
Weight loss	in kilograms	at 6 and 12 weeks, and 6 and 12 months post RT
Patient reported pain	Measured by NRS-scale	at 6 and 12 weeks, and 6 and 12 months post RT
Patient reported Quality of Life	QLQ-C30 questionnaire	at 6 and 12 weeks, and 6 and 12 months post RT
Muscle strength	measured using chest press and leg press	at 6 and 12 weeks, and 6 and 12 months post RT
Chair rise	measured using 30 s. chair rise	at 6 and 12 weeks, and 6 and 12 months post RT
arm curls	measured using 30 s. arm curls	at 6 and 12 weeks, and 6 and 12 months post RT
Stair climb	steps/sec	at 6 and 12 weeks, 6 and 12 months
Compliance to PRT program	No. of attended sessions out of total	at 12 weeks post PRT
Physical activity	measured by PAS (physical activity scale)	at 6 and 12 weeks, and 6 and 12 months post RT
Percent of patients with feeding tubes		at 6 and 12 weeks, and 6 and 12 months post RT
Resumption of work	No. of days from end of radiotherapy until back at work at full time (or the hours of work per week as before therapy)	At 12 months follow-up
Percent relapses	Percent of patients having relapse within 12 months after radiotherapy	at 12 months follow-up
Cytokines	Measurement of different cytokines, changes over time and after bout of PRT. Will be measured regularly during the 12 weeks of PRT.	at 3, 6, 8, 10, and 12 weeks
Muscle biopsies	protein will be measured using the proteomic approach. Muscle fiber type and size will be evaluated.	at 6 and 12 weeks, and at 12 months follow-up
Patient satisfaction	Study specific questionnaire regarding pros and cons of attending the study	at 12 weeks
NK-cells	Measuring NK-cells. NK-cells may increase after exercise and show tumor inhibiting effect.	at 3 and 12 weeks

Collaborators and Investigators

• Sponsor: Herlev Hospital
• Collaborators: Odense University Hospital; Aarhus University Hospital; Danish Head and Neck Cancer Group
• Investigators: Principal Investigator: Julie Gehl, Herlev Hospital

Publications and helpful links

General Publications

• Lonkvist CK, Lonbro S, Vinther A, Zerahn B, Rosenbom E, Primdahl H, Hojman P, Gehl J. Progressive resistance training in head and neck cancer patients during concomitant chemoradiotherapy -- design of the DAHANCA 31 randomized trial. BMC Cancer. 2017 Jun 3;17(1):400. doi: 10.1186/s12885-017-3388-0.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: September 11, 2015
• First Submitted That Met QC Criteria: September 22, 2015
• First Posted (Estimate): September 23, 2015

Study Record Updates

• Last Update Posted (Actual): May 27, 2020
• Last Update Submitted That Met QC Criteria: May 23, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Exercise Training; Weight loss; Body Composition; Progressive Resistance Training; Lean Body Mass; Concomitant chemoradiotherapy
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Body Weight; Body Weight Changes; Head and Neck Neoplasms; Weight Loss
• Other Study ID Numbers: DAHANCA 31