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.
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
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),
Parallel
Physical activity recommendations
BehavioralAt the baseline, all participants will receive the international recommendations in terms of physical activity for promoting health in the general population.
Connected activity tracker
BehavioralAt 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.
Physical Activity (PA) Intervention
BehavioralThe 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 at a moderate intensity. Patients will be offered different options of PA practice: in the supervised collective live online PA session (as already performed in the phase 1), and/or in a fitness center (this practice will take place in a "classic" environment with a 9-month free access for patients thanks to a partnership), and/or self-practice. In addition, patients will benefit from 4 individual motivational interviews, conducted by videoconference and/or by phone call with a professional.
cancer-related fatigue, considering both physical and cognitive fatigue scores at 3 years after the start of first-line chemotherapy
Multidimensional aspects of fatigue will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-FA12 cancer related fatigue module. EORTC QLQ-FA12 consists of 12 items to evaluated physical, cognitive and emotional domains of cancer-related fatigue. Participants will answer to a 4-points Likert scale ranging from "not at all" to "very much". All scores will be transformed to a 0 to 100 scale and higher scores will indicate greater degree of fatigue. The Primary Outcome Measure will be assessed with physical and cognitive items.
other dimensions of fatigue
Multidimensional aspects of fatigue will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-FA12 cancer related fatigue module. EORTC QLQ-FA12 consists of 12 items to evaluated physical, cognitive and emotional domains of cancer-related fatigue. Participants will answer to a 4-points Likert scale ranging from "not at all" to "very much". All scores will be transformed to a 0 to 100 scale and higher scores will indicate greater degree of fatigue. All of the secondary cancer related fatigue dimensions except the physical and cognitive items are evaluated (emotional fatigue, interference with daily life and social sequelae, assessed by the EORTC QLQ-FA12 questionnaire).
Health-related quality of life (EORTC QLQ-C30)
Health-Related Quality of Life (HRQoL) and fatigue will be measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality Of Life Questionnaire (QLQ-C30). QLQ-C30 questionnaire consists of 30 items to evaluate 5 functioning domains (physical, role, emotional, cognitive, and social), a global HRQoL domain, 3 symptom domains (pain, fatigue and nausea) and 6 single items (dyspnea, insomnia, anorexia, diarrhea, constipation and financial impact).Participants will answer to a Likert scale ranging from "not at all" to "very much" and from "very bad" to "excellent" only for the global HRQoL questions. All scores will be standardized to a 0 to 100 scale according to the EORTC scoring manual. Higher scores represent better functioning, better global HRQoL and greater symptom burden.
Health-related quality of life specific for testicular cancer (EORTC QLQ-TC26)
The module Quality of Life Questionnaire specific to Testicular Cancer (QLQ-TC26) comprises seven multi-item scales (treatment side effects, treatment satisfaction, future perspective, communication, sexual activity, functioning and enjoyment) and six single items (job and education problems, physical limitations, family problems, infertility, body image problems, testicular transplant satisfaction).Participants will answer to a Likert scale ranging from "not at all" to "very much". All scores will be standardized to a 0 to 100 scale according to the EORTC scoring manual. Higher scores represent better functioning, better global HRQoL and greater symptom burden.
Proportion of patients who modify their cognition
The cancer-related cognitive impairment will be measured by the Functional Assessment of Cancer Therapy-Cognition (FACT-Cog). The FACT-Cog is a validated self-administrated questionnaire in order to assess memory, attention, concentration, language, and thinking abilities. The questionnaire is composed of 37 items with four subscales: patients' perceived cognitive impairments, perceived cognitive abilities, deficits observed or commented on by others, and impact of cognitive changes on HRQoL. Participant will answer how often this situation occurred during the last 7 days on a Likert-type scale ranging from "never" to "several times a day". For both scales, higher scores indicated better perceived cognitive function.
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Centre Leon Berard
Lead sponsor
National Cancer Institute, France
Collaborator
