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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Testicular Cancer
• Intervention / Treatment: Behavioral: Physical activity recommendations; Behavioral: Connected activity tracker; Behavioral: Physical Activity (PA) Intervention

• Study Type: Interventional
• Enrollment (Estimated): 236
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carmen Dupuis, PhD; Phone Number: +33 0469856218; Email: carmen.dupuis@lyon.unicancer.fr
• Study Contact Backup: Name: Olivia Pérol, PhD; Phone Number: +33 0478782897; Email: olivia.perol@lyon.unicancer.fr

Study Locations

• France
  • Angers, France, 49000
    • Not yet recruiting
    • Institut de Cancerologie de Lorraine
    • Sub-Investigator: Elouen BOUGHALEM, MD
    • Principal Investigator: Sophie ABADIE-LACOURTOISIE, MD
    • Contact: Sophie ABADIE-LACOURTOISIE, MD; Phone Number: 0241352700; Email: sophie.abadie-lacourtoisie@ico.unicancer.fr
    • Sub-Investigator: Rémi DELVA, MD
  • Besançon, France, 25030
    • Not yet recruiting
    • Chu Jean Minjoz
    • Sub-Investigator: Fabien CALCAGNO, MD
    • Sub-Investigator: Thierry N'GUYEN, MD
    • Sub-Investigator: Antoine THIERRY VUILLEMIN, MD
    • Sub-Investigator: Elsa KALBACHER, MD
    • Contact: Elodie KLAJER, MD
    • Sub-Investigator: Guillaume MOUILLET, MD
    • Principal Investigator: Elodie KLAJER, MD
  • Bordeaux, France, 33000
    • Not yet recruiting
    • Institut Bergonie
    • Contact: Mathilde CABART, MD
    • Principal Investigator: Mathilde CABART, MD
    • Sub-Investigator: Diego TEYSSONNEAU, MD
    • Sub-Investigator: Guilhem ROUBAUD, MD
  • Caen, France, 14076
    • Not yet recruiting
    • Centre Francois Baclesse
    • Contact: Florence JOLY, Pr, MD
    • Principal Investigator: Florence JOLY, Pr, MD
    • Sub-Investigator: Isabelle BONNET, MD
    • Sub-Investigator: Emeline MERIAUX, MD
  • Lille, France, 59020
    • Not yet recruiting
    • Centre Oscar Lambret
    • Contact: Guillaume CARBONNELLE, MD
    • Principal Investigator: Guillaume CARBONNELLE, MD
  • Lyon, France, 69008
    • Recruiting
    • Centre Léon Bérard
    • Principal Investigator: Aude FLECHON, MD
    • Contact: Aude FLECHON, MD; Phone Number: + 33 478 78 26 43; Email: aude.flechon@lyon.unicancer.fr
  • Nancy, France, 54519
    • Recruiting
    • Institut de Cancerologie de Lorraine
    • Contact: Lionnel Goeffrois, MD
    • Sub-Investigator: Albane LHUILLIER, MD
    • Sub-Investigator: Camille SIMON, MD
    • Sub-Investigator: Vincent MASSARD, MD
    • Principal Investigator: Sophie MARTIN, MD
  • Nice, France, 06189
    • Not yet recruiting
    • Centre Antoine Lacassagne
    • Contact: Agnès DUCOULOMBIER, MD
    • Principal Investigator: Agnès DUCOULOMBIER, MD
  • Paris, France, 75020
    • Not yet recruiting
    • AP-HP Tenon
    • Contact: Jean-Pierre LOTZ, MD; Phone Number: 0156016058; Email: jean-pierre.lotz@aphp.fr
    • Principal Investigator: Jean-Pierre LOTZ, MD
    • Sub-Investigator: Mathieu JAMELOT, MD
  • Rennes, France, 35000
    • Not yet recruiting
    • Centre Eugene Marquis
    • Contact: Christophe MASSARD, PhD, MD
    • Principal Investigator: Christophe MASSARD, PhD, MD
    • Sub-Investigator: Laurence CROUZET, MD
    • Sub-Investigator: Brigitte LAGUERRE, MD
  • Tours, France, 37000
    • Not yet recruiting
    • CHU Tours
    • Sub-Investigator: Bérengère NARCISO, MD
    • Principal Investigator: Mathilde CANCEL, MD
    • Contact: Mathilde CANCEL, MD; Phone Number: 0247477393; Email: m.cancel@chu-tours.fr
    • Sub-Investigator: Florian CARNEIRO, MD
    • Sub-Investigator: Fanny VAREILLE, MD
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
    • Contact: Anna PATRIKIDOU, MD; Phone Number: 0142115947; Email: Anna.PATRIKIDOU@gustaveroussy.fr
    • Principal Investigator: Anna PATRIKIDOU, MD
    • Sub-Investigator: Karim FIZAZI, MD
    • Sub-Investigator: Natacha NAOUN, MD
    • Sub-Investigator: Jacopo ULIANO, MD
    • Sub-Investigator: Cédric POBEL, MD
    • Sub-Investigator: Alexandre MEGHERBI, MD
    • Sub-Investigator: Yohann LORIOT, MD
    • Sub-Investigator: Alina FUEREA, MD
    • Sub-Investigator: Ronan FLIPPOT, MD
    • Sub-Investigator: Mario DI PALMA, MD
    • Sub-Investigator: Solenn BARRAUD, MD
    • Sub-Investigator: Karim AMRANE, MD

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group	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 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.
Active Comparator: Control group	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Year 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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)	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.	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)	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.	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	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.	Inclusion, end of chemotherapy (Month 4), Month 12, Year 2, Year 3
Proportion of patients who modify their anxiety and depression level	Hospital Anxiety and Depression scale (HADS) is an instrument used to screen for anxiety and depressive disorders. It has 14 rated items from 0 to 3. Seven questions relate to anxiety (total A) and seven others to the depressive dimension (total D), allowing thus obtaining two scores (maximum score for each score = 21).	Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3
Proportion of patients who change their anthropometry	Weight (in kilograms), Height (in meters), Body Mass Index (in kg/m^2)	Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3
Physical condition and muscular strength (6-minute walk test)	assessed by the 6-minute walk test (distance traveled in meters in 6 minutes)	Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3
Physical condition and muscular strength (hand-grip)	assessed by the hand-grip test (kg)	Inclusion, end of chemotherapy (Month 4), Month 6, Month 12, Year 2, Year 3
Physical condition and muscular strength (sit-to-stand test)	assessed by the sit-to-stand test (number of repetitions)	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	PA and sedentary levels will be measured by National Observatory of Physical Activity and Sedentary Lifestyle - Physical Activity questionnaire (ONAPS-PAQ) This questionnaire assesses the level of physical activity and sedentary lifestyle during a typical week for the adult population. It is divided into three parts and 21 questions: activities at work, travel for utilitarian purposes and leisure or home activities. This questionnaire also assesses physical inactivity at all times of life (travel, work, leisure).	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	number of days wearing the tracker	Every days during the first year
Adherence to the physical activity tracker	number of days wearing the tracker	Month 12
Satisfaction with the intervention	self-administered questionnaire	Month 12
sleep quality and heart rate	assessed by the connected watch	continuously during the first year
compliance with PA sessions	assessed by the number of sessions scheduled/performed during the different phases of the intervention	Month 12
Motivation	This questionnaire can be used on a daily basis, for all populations, with the aim of better understanding the motivation of individuals to practice physical activities from a health perspective. The challenge is to provide professionals with an appropriate questionnaire that can assess patient motivation at the start and end of PA care. Participants will answer to a 7-points Likert scale ranging from "does not match at all" to "corresponds very strongly". This questionnaire assesses several items : intrinsic motivation, integrated regulation, identified regulation, introjected regulation, external regulation, amotivation. The results for each patient should be compared with the results of the validation population.	Inclusion, end of chemotherapy (Month 4), Month 12
pre-intervention PA practice environment	The association between the pre-intervention PA practice environment (type of activity, practice locations) and compliance with the intervention	Inclusion
Number of participants with neuropathies and the neuropathies level	Neuropathies assessed by a visual analog scale. Participants will answer to a 0 (better outcome) to 10 (worst outcome) scale.	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
Number of participants with pain and the pain level	Pain assessed by a visual analog scale. Participants will answer to a 0 (better outcome) to 10 (worst outcome) scale.	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
TGCT relapse	CT scan/tumor-marker increase	Month 12, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9, Year 10
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Occurrence of induced-treatment toxicity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE)	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
Second primary malignancy	The occurence of second primary malignancy	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
Sustainable return to work	number of consecutive working days without sick leave	Month 12, Year 2, Year 3
Immune and inflammatory biomarkers	IL-1α/β, IL-6, IL-15, TNF-α, CRP	Inclusion, end of chemotherapy (Month 4), Month 12, Year 3
liver function biomarkers	ALT/AST, bilirubin	Inclusion, end of chemotherapy (Month 4), Month 12, Year 3
gut microbiota composition and diversity	measured using 16s rRNA Illumina sequencing	Inclusion, end of chemotherapy (Month 4), Month 12, Year 3
french validation of EORTC QLQ-TC26	To validate the psychometric properties of the French version of the EORTC QLQ-TC26 questionnaire assessing the health-related health-related quality of life in patients with testicular cancer	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
a sociological study on patient engagement in physical activity	The sociological approach will combine ethnographic research with semi-structured interviews with patients and healthcare professionals involved in the study. The ethnographic research will begin during the enrollment phase and will take place during interdisciplinary meetings, treatment sessions, physical activity initiation sessions, and end-of-session meetings. This study will be proposed only for 30 Patients of CLB and IGR, and they have to do two interviews.	Inclusion, Month 12

Collaborators and Investigators

• Sponsor: Centre Leon Berard
• Collaborators: National Cancer Institute, France
• Investigators: Principal Investigator: Aude Fléchon, MD, Centre Léon Bérard

Publications and helpful links

General 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 phase-III STARTER trial. BMC Cancer. 2024 Jan 15;24(1):84. doi: 10.1186/s12885-024-11824-7.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2025
• Primary Completion (Estimated): January 14, 2031
• Study Completion (Estimated): January 14, 2038

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 20, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: fatigue; sequelae; gut microbiota composition
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Male Urogenital Diseases; Endocrine Gland Neoplasms; Gonadal Disorders; Testicular Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Fatigue; Testicular Neoplasms; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Exercise; Methods
• Other Study ID Numbers: STARTER (ET 22-125)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No