Impact of a Physical Activity Program to Reduce Long-term Cancer-related Fatigue in Metastatic Testicular Germ Cell Tumor Patients

Official title

A National, Multicenter, Phase III Randomized Controlled Trial to Assess the Impact of a One-year Supervised Physical Activity Program to Reduce Long-term Cancer-related Fatigue in Metastatic Testicular Germ Cell Tumor Patients

Overview

Testicular germ cell tumor (TGCT) is the most common malignancy in men between 15 and 40 years. Although TCGT survivors have a good survival prognosis, they suffer from short- and long-term sequelae such as chronic fatigue, psychological disorders, cardiovascular toxicities and second malignancies. The benefits of physical activity (PA) during treatments have been demonstrated in cancer patients to improve quality of life (QoL) and physical fitness and to reduce fatigue. However, few PA programs have been proposed to TGCT patients and their effects on sequelae have not been assessed yet. A growing body of evidence links treatment-related alteration in the gut microbiota to sequelae of cancer survivors, including fatigue and cardiovascular toxicities. Also, PA has been known as a possible modulator of the gut microbiota composition. To date, no study has been conducted to examine how the gut microbiota and its metabolites moderate the effect of PA on fatigue and other late effects in TGCT survivors. The objectives will be to assess the impact of a PA program on fatigue and other sequelae and to investigate how the gut microbiota and its metabolites moderate the associations between PA and sequelae. We will conduct a prospective, multicenter, phase III, randomized controlled trial of a one-year supervised PA program. 236 men with metastatic TGCT and eligible for a first line of chemotherapy will be randomly assigned to either PA intervention or control arm. All patients will benefit from a connected activity tracker and PA recommendations. In the intervention arm, PA will be based on supervised sessions and motivational interviews. The primary endpoint (fatigue) will be assessed at 3 years. The trial will provide novel insights into the impact of PA on fatigue and other sequelae in TGCT survivors with understanding a potential underlying mechanism of gut microbiota. This evidence will support the development of targeted PA guidelines to improve QoL and reduce sequelae in TGCT survivors.

Interventions

• Behavioral Physical activity recommendations
  At the baseline, all participants will receive the international recommendations in terms of physical activity for promoting health in the general population.
• Behavioral Connected activity tracker
  At baseline, all participants will receive a connected activity tracker to wear 24 hours a day during one year. Patients will be asked to download an application, dedicated to the study so that the physical activity data (ie. number of steps per day) will be synchronized in the application.
• Behavioral Physical Activity (PA) Intervention
  The intervention will last 1 year and will have 2 phases. Phase 1: At each cycle of chemotherapy, patients will be proposed to perform 2-4 sessions per week. This program will be individual, supervised, performed at a moderate intensity. Between cycles, patients will be asked to perform 1-2 supervised collective live online physical activity sessions per week, proposed by a partner specialized in online PA. Phase 2: After chemotherapy, patients will be asked to perform 2-3 PA sessions per week

Primary outcome measures

• cancer-related fatigue, considering both physical and cognitive fatigue scores at 3 years after the start of first-line chemotherapy [Time frame: Year 3]

Secondary outcome measures (12)

• other dimensions of fatigue [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9, Year 10]
• Health-related quality of life (EORTC QLQ-C30) [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9, Year 10]
• Health-related quality of life specific for testicular cancer (EORTC QLQ-TC26) [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9, Year 10]
• Proportion of patients who modify their cognition [Time frame: Inclusion, end of chemotherapy (Month 4), Month 12, Year 2, Year 3]
• Proportion of patients who modify their anxiety and depression level [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3]
• Proportion of patients who change their anthropometry [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3]
• Physical condition and muscular strength (6-minute walk test) [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3]
• Physical condition and muscular strength (hand-grip) [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3]
• Physical condition and muscular strength (sit-to-stand test) [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3]
• Proportion of patients who change their physical activity (PA) and sedentary levels [Time frame: Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9, Year 10]
• Physical activity level [Time frame: Every days during the first year]
• Adherence to the physical activity tracker [Time frame: Month 12]

Eligibility criteria

Inclusion criteria

• Men ≥18 years
• With a metastatic germ cell tumor histologically confirmed (seminoma and non-seminoma)
• Who have already undergone an orchidectomy (since the 16th december, this criteria was deleted).
• Having a first line of chemotherapy planned with BEP, EP or VIP
• Having a smartphone (i.e. to connect the activity tracker)
• PS < or = 2
• Whose ability to practice an adapted physical activity (APA) has been certified by a medical certificate issued by the referring oncologist or the investigating physician
• Available and willing to participate in the study for the duration of the intervention and follow-up,
• Able to understand, read and write French,
• Affiliated with a social security scheme,
• Having dated and signed an informed consent.

Exclusion criteria

• Presence of symptomatic bone and/or brain metastases
• Central nervous system involvement with neurological deficits preventing walking
• History or coexistence of another primary cancer (apart from in situ cancer of any location and/or basal cell skin cancer and/or basal cell skin cancer and/or a cancer in complete remission for more than 3 years),
• Contraindication to physical activity (e.g. uncontrolled hypertension, uncontrolled heart disease) uncontrolled heart disease),
• Unable to be followed for medical, social, family, geographical or psychological reasons, during the entire study period,
• Deprived of liberty by judicial or administrative decision, or adults protected by law,
• Concurrent participation in another study in PA.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

France · 12 centers

• Institut de Cancérologie de Lorraine — Angers
• CHU Jean Minjoz — Besançon
• Institut Bergonié — Bordeaux
• Centre François Baclesse — Caen
• Centre Oscar Lambret — Lille
• Centre Leon Berard — Lyon
• Institut de Cancérologie de Lorraine — Nancy
• Centre Antoine Lacassagne — Nice
• … and 4 more centers

Publications

• Noh H, Anota A, Mongondry R, Meyrand R, Dupuis C, Schiffler C, Marijnen P, Rinaldi S, Lachuer J, Keski-Rahkonen P, Gunter MJ, Flechon A, Fervers B, Perol O. Impact of a one-year supervised physical activity program on long-term cancer-related fatigue and mediating effects of the gut microbiota in metastatic testicular cancer patients: protocol of the prospective multicentre, randomized controlled PMID 38225551

Identifiers

NCT: NCT05588700 · STARTER (ET 22-125)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗