Clinical trial NCT04625907: FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma
Official title: FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Rhabdomyosarcoma
Lead sponsor: University of Birmingham
Sponsor class: OTHER
First posted: 2020-11-12
Enrollment: 1672
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: FaR-RMS is an over-arching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS)

Detailed description: FaR-RMS is an over-arching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS). It is a multi-arm, multi-stage format, involving several different trial questions. FaR-RMS is intended to be a rolling programme of research with new treatment arms being introduced dependant on emerging data and innovation. This study has multiple aims. It aims to evaluate the impact of new agent regimens in both newly diagnosed and relapsed RMS; whether changing the duration of maintenance therapy affects outcome; and whether changes to dose, extent (in metastatic disease) and timing of radiotherapy improve outcome and quality of life. In addition the study will evaluate risk stratification through the use of PAX-FOXO1 fusion gene status instead of histological subtyping and explore the use of FDG PET-CT response assessment as a prognostic biomarker for outcome following induction chemotherapy.

Newly diagnosed patients should, where possible, be entered into the FaR-RMS study at the time of first diagnosis prior to receiving any chemotherapy. However, patients can enter at the point of radiotherapy or maintenance, and those with relapsed disease can enter the study even if not previously entered at initial diagnosis. Patients may be entered into more than one randomisation/registration, dependant on patient risk group and disease status.

Eligibility criteria: Inclusion Criteria for study entry - Mandatory at first point of study entry

1. Histologically confirmed diagnosis of RMS (except pleomorphic RMS)
2. Written informed consent from the patient and/or the parent/legal guardian

Phase 1b Dose Finding - IRIVA Inclusion

1. Entered in to the FaR-RMS study at diagnosis
2. Very High Risk disease
3. Age \>12 months and ≤25 years
4. No prior treatment for RMS other than surgery
5. Medically fit to receive treatment
6. Adequate hepatic function:

   1. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age, unless the patient is known to have Gilbert's syndrome
   2. ALT or AST \< 2.5 X ULN for age
7. Absolute neutrophil count ≥1.0x 109/L
8. Platelets ≥ 80 x 109/L
9. Adequate renal function: estimated or measured creatinine clearance ≥60 ml/min/1.73 m2
10. Documented negative pregnancy test for female patients of childbearing potential
11. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active
12. Written informed consent from the patient and/or the parent/legal guardian

Exclusion

1. Weight \<10kg
2. Active \> grade 2 diarrhoea
3. Prior allo- or autologous Stem Cell Transplant
4. Uncontrolled inter-current illness or active infection
5. Pre-existing medical condition precluding treatment
6. Urinary outflow obstruction that cannot be relieved prior to starting treatment
7. Active inflammation of the urinary bladder (cystitis)
8. Known hypersensitivity to any of the treatments or excipients
9. Second malignancy
10. Pregnant or breastfeeding women

Frontline chemotherapy randomisation Very High Risk - CT1a Inclusion

1. Entered in to the FaR-RMS study at diagnosis
2. Very High Risk disease
3. Age ≥ 6 months
4. Available for randomisation ≤60 days after diagnostic biopsy/surgery
5. No prior treatment for RMS other than surgery
6. Medically fit to receive treatment
7. Adequate hepatic function :

   a. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age, unless the patient is known to have Gilbert's syndrome
8. Absolute neutrophil count ≥1.0x 109/L (except in patients with documented bone marrow disease)
9. Platelets ≥ 80 x 109/L (except in patients with documented bone marrow disease)
10. Fractional Shortening ≥ 28%
11. Documented negative pregnancy test for female patients of childbearing potential
12. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active
13. Written informed consent from the patient and/or the parent/legal guardian

Exclusion

1. Active \> grade 2 diarrhoea
2. Prior allo- or autologous Stem Cell Transplant
3. Uncontrolled inter-current illness or active infection
4. Pre-existing medical condition precluding treatment
5. Urinary outflow obstruction that cannot be relieved prior to starting treatment
6. Active inflammation of the urinary bladder (cystitis)
7. Known hypersensitivity to any of the treatments or excipients
8. Second malignancy
9. Pregnant or breastfeeding women

Frontline chemotherapy randomisation High Risk - CT1b Inclusion

1. Entered in to the FaR-RMS study at diagnosis
2. High Risk disease
3. Age ≥ 6 months
4. Available for randomisation ≤60 days after diagnostic biopsy/surgery
5. No prior treatment for RMS other than surgery
6. Medically fit to receive treatment
7. Adequate hepatic function :

   a. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age, except if the patient is known to have Gilbert's syndrome
8. Absolute neutrophil count ≥1.0x 109/L
9. Platelets ≥ 80 x 109/L
10. Documented negative pregnancy test for female patients of childbearing potential
11. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active
12. Written informed consent from the patient and/or the parent/legal guardian

Exclusion

1. Active \> grade 2 diarrhoea
2. Prior allo- or autologous Stem Cell Transplant
3. Uncontrolled inter-current illness or active infection
4. Pre-existing medical condition precluding treatment
5. Urinary outflow obstruction that cannot be relieved prior to starting treatment
6. Active inflammation of the urinary bladder (cystitis)
7. Known hypersensitivity to any of the treatments or excipients
8. Second malignancy
9. Pregnant or breastfeeding women

Frontline Radiotherapy Note: eligible patients may enter multiple radiotherapy randomisations.

Radiotherapy Inclusion - for all radiotherapy randomisations

1. Entered in to the FaR-RMS study (at diagnosis or prior to radiotherapy randomisation)
2. Very High Risk, High Risk and Standard Risk disease
3. ≥ 2 years of age
4. Receiving frontline induction treatment as part of the FaR-RMS trial or with a IVA/IVADo based chemotherapy regimen patients for whom. Note that patients for whom ifosfamide has been replaced with cyclophosphamide will be eligible
5. Patient assessed as medically fit to receive the radiotherapy
6. Documented negative pregnancy test for female patients of childbearing potential
7. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active
8. Written informed consent from the patient and/or the parent/legal guardian

Radiotherapy Exclusion - for all radiotherapy randomisations

1. Prior allo- or autologous Stem Cell Transplant
2. Second malignancy
3. Pregnant or breastfeeding women
4. Receiving radiotherapy as brachytherapy

RT1a Specific Inclusion

1. Primary tumour deemed resectable (predicted R0/ R1 resection feasible) after 3 cycles of induction chemotherapy (6 cycles for metastatic disease)
2. Adjuvant radiotherapy required in addition to surgical resection (local decision).
3. Available for randomisation after cycle 3 and prior to the start of cycle 6 of induction chemotherapy for localised disease, or after cycle 6 and prior to the start of cycle 9 for metastatic disease

RT1b Specific Inclusion

1. Primary tumour deemed resectable (predicted R0/R1 resection) after 3 cycles of induction chemotherapy (6 cycles for metastatic disease).
2. Adjuvant radiotherapy required in addition to surgical resection (local decision)
3. Higher Local Failure Risk (HLFR) based on presence of either of the following criteria:

   1. Unfavourable site
   2. Age ≥ 18yrs
4. Available for randomisation after cycle 3 and prior to the start of cycle 6 of induction chemotherapy for localised disease, or after cycle 6 and prior to the start of cycle 9 for metastatic disease

RT1c Specific Inclusion

1. Primary radiotherapy indicated (local decision)
2. Higher Local Failure Risk (HLFR) based on either of the following criteria:

   1. Unfavourable site
   2. Age ≥ 18yrs
3. Available for randomisation after cycle 3 and prior to the start of cycle 6 of induction chemotherapy for localised disease, or after cycle 6 and prior to the start of cycle 9 for metastatic disease

RT2

1. Available for randomisation after cycle 6 and before the start of cycle 9 of induction chemotherapy.
2. Unfavourable metastatic disease, defined as Modified Oberlin Prognostic Score 2-4

   * Note: Definition of metastatic lesions for RT2 eligibility

Modified Oberlin Prognostic Score (1 point for each adverse factor):

* Age ≥10y
* Extremity, Other, Unidentified Primary Site
* Bone and/ or Bone Marrow involvement
* ≥3 metastatic sites

Unfavourable metastatic disease: 2- 4 adverse factors Favourable metastatic disease: 0-1 adverse factors

Maintenance chemotherapy (Very High Risk) - CT2a Inclusion Randomisation must take place during the 12th cycle of maintenance chemotherapy.

1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. Very High Risk disease
3. Received frontline induction chemotherapy as part of the FaR-RMS trial or with a IVA/IVADo based chemotherapy regimen

   a. Patients for whom ifosfamide has been replaced with cyclophosphamide will be eligible
4. Completed 11 cycles of VnC maintenance treatment (either oral or IV regimens)
5. No evidence of progressive disease
6. Absence of severe vincristine neuropathy - i.e requiring discontinuation of vincristine treatment)
7. Medically fit to continue to receive treatment
8. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active
9. Written informed consent from the patient and/or the parent/legal guardian

Exclusion

1. Prior allo- or autologous Stem Cell Transplant
2. Uncontrolled intercurrent illness or active infection
3. Urinary outflow obstruction that cannot be relieved prior to starting treatment
4. Active inflammation of the urinary bladder (cystitis)
5. Second malignancy
6. Pregnant or breastfeeding women

Maintenance chemotherapy (High Risk) - CT2b Randomisation must take place during the 6th cycle of maintenance chemotherapy. Inclusion

1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. High Risk disease
3. Received frontline induction chemotherapy as part of the FaR-RMS trial or with a IVA based chemotherapy regimen. Note that patients for whom ifosfamide has been replaced with cyclophosphamide will be eligible
4. Completed 5 cycles of VnC maintenance treatment
5. No evidence of progressive disease
6. Absence of severe vincristine neuropathy i.e. requiring discontinuation of vincristine treatment
7. Medically fit to continue to receive treatment
8. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active
9. Written informed consent from the patient and/or the parent/legal guardian

Exclusion

1. Prior allo- or autologous Stem Cell Transplant
2. Uncontrolled inter current illness or active infection
3. Urinary outflow obstruction that cannot be relieved prior to starting treatment
4. Active inflammation of the urinary bladder (cystitis)
5. Second malignancy
6. Pregnant or breastfeeding women

CT3 Relapsed Chemotherapy

Inclusion:

1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. First or subsequent relapse of histologically verified RMS
3. Age ≥ 6 months
4. Measurable or evaluable disease
5. No cytotoxic chemotherapy or other investigational medicinal product (IMP) within previous three weeks: within two weeks for vinorelbine and cyclophosphamide maintenance chemotherapy
6. Medically fit to receive trial treatment
7. Documented negative pregnancy test for female patients of childbearing potential within 7 days of planned randomisation
8. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active
9. Written informed consent from the patient and/or the parent/legal guardian

Exclusion:

1. Progression during frontline therapy without previous response (=Refractory to first line treatment)
2. Prior regorafenib or temozolomide
3. Active \> grade 1 diarrhoea
4. ALT or AST \>3.0 x upper limit normal (ULN)
5. Bilirubin, Total \>1.5 x ULN; total bilirubin is allowed up to 3 x ULN if Gilbert's syndrome is documented
6. Patients with unstable angina or new onset angina (within 3 months of planned date of randomisation), recent myocardial infarction (within 6 months of randomisation) and those with cardiac failure New York Heart Association (NYHA) Classification 2 or higher Cardiac abnormalities such as congestive heart failure (Modified Ross Heart Failure Classification for Children = class 2) and cardiac arrhythmias requiring antiarrhythmic therapy (beta blockers or digoxin are permitted)
7. Uncontrolled hypertension \> 95th centile for age and gender
8. Prior allo- or autologous Stem Cell Transplant
9. Uncontrolled inter-current illness or active infection
10. Pre-existing medical condition precluding treatment
11. Known hypersensitivity to any of the treatments or excipients
12. Second malignancy
13. Pregnant or breastfeeding women

Primary outcomes:
measure: Event Free Survival (RT2)
timeFrame: From randomisation to first failure event, timeframe 36 months
measure: Event Free Survival (CT1A)
timeFrame: From randomisation to first failure event, timeframe 36 months
measure: Event Free Survival (CT1B)
timeFrame: From randomisation to first failure event, timeframe 36 months
measure: Event Free Survival (CT2A)
timeFrame: From randomisation to first failure event, timeframe 36 months
measure: Event Free Survival (CT2B)
timeFrame: Time from randomisation to first failure event, timeframe 36 months
measure: Event Free Survival (CT3)
timeFrame: Patients will be followed up for a minimum of 6 years from trial entry (or 5 years from end of relapsed trial treatment, whichever comes later). Patients will be followed up for progression and death until the end of trial definition has been met.
measure: Local Failure Free Survival (RT1A and RT1B)
timeFrame: Time from randomisation to first local failure event, timeframe 36 months
measure: Local Failure Free Survival (RT1C)
timeFrame: Time from randomisation to first local failure event, timeframe 36 months
Secondary outcomes:
measure: Recommended Phase II Dose (Phase 1b)
timeFrame: From first patient first visit in dose finding study until appropriate dose level found, estimated 9 months
measure: Maximum Tolerated Dose (Phase 1b)
timeFrame: From first patient first visit in dose finding study until appropriate dose level
measure: Toxicity (All chemotherapy randomisations)
timeFrame: From date of protocol defined treatment until 30 days after the administration of the last treatment
measure: Dose Limiting Toxicity (Phase 1b)
timeFrame: From commencement of treatment until 21 days after the start of cycle 2 (each cycle is 21 days)
measure: Response (Phase 1b, CT1A, CT1B)
timeFrame: Response assessed after course 3 (63 days) and 6 (126 days)
measure: Tolerability (CT3)
timeFrame: From registration/randomisation until death/study endpoint
measure: Overall Survival (CT1A)
timeFrame: From randomisation to death from any cause, assessed for 36 months
measure: Overall Survival (CT1B)
timeFrame: From randomisation to death from any cause, assessed for 36 months
measure: Overall Survival (CT2A)
timeFrame: From randomisation to death from any cause, assessed for 36 months
measure: Overall Survival (CT2B)
timeFrame: From randomisation to death from any cause, assessed for 36 months
measure: Overall Survival (RT1A and RT1B)
timeFrame: From randomisation to death from any cause, assessed for 36 months
measure: Overall Survival (RT1C)
timeFrame: From RT1C randomisation to death from any cause, assessed for 36 months
measure: Overall Survival (RT2)
timeFrame: From RT2 randomisation to death from any cause, as assessed for 36 months
measure: Overall Survival (CT3)
timeFrame: Patients will be followed up for a minimum of 6 years from trial entry (or 5 years from end of relapsed trial treatment, whichever comes later). Patients will be followed up for progression and death until the end of trial definition has been met.
measure: Overall Survival (all patients)
timeFrame: From randomisation/registration to death from any cause, assessed for 36 months
measure: Acute wound complications and post-operative complications (RT1A and RT1B)
timeFrame: Within 120 days from surgery
measure: Acute post-radiotherapy complications (All radiotherapy randomisations)
timeFrame: Within 120 days from start of radiotherapy
measure: Late complications (RT1A, RT1B. RT1C)
timeFrame: After 120 days from last local therapy
measure: Loco-regional failure-free survival (All radiotherapy randomisations)
timeFrame: From randomisation to first local and/or regional failure event, assessed for 36 months
measure: Health related quality of life (RT1A and RT2) self-reported questionnaire completed by patient
timeFrame: 4 timepoints: 1) 1 day of start of radiotherapy, 2) at completion of radiotherapy, average 5 weeks after start of radiotherapy, 3) 3 months and 4) 24 months following radiotherapy
measure: Health related quality of life (RT1A and RT2) self-reported questionnaire completed by the patient
timeFrame: 4 timepoints: 1) 1 day of start of radiotherapy, 2) at completion of radiotherapy, average 5 weeks after start of radiotherapy, 3) 3 months and 4) 24 months following radiotherapy
measure: Health related quality of life (CT3) self-reported questionnaire completed by the patient
timeFrame: 3 timepoints: Each Cycle is 28 days. Timepoint 1: Day 0 of cycle 1 (prior to starting treatment), Timepoint 2 day 0 cycle 3, Timepoint 3) day 0 cycle 5
measure: Health related quality of life (CT3) self-reported questionnaire completed by the patient
timeFrame: 3 timepoints: Each Cycle is 28 days. Timepoint 1: Day 0 of cycle 1 (prior to starting treatment), Timepoint 2 day 0 cycle 3, Timepoint 3) day 0 cycle 5
measure: Acceptability and Palatability of Regorafenib (CT3)
timeFrame: 1 timepoint: Day 8 of cycle 1 (Each Cycle is 28 days)
measure: PET Response (if participating in PET Sub-study)
timeFrame: After three cycles of chemotherapy (each cycle is 21 days)
measure: Event Free Survival (all patients)
timeFrame: From date of randomisation/registration to death from any cause, assessed for 36 months
measure: Event Free Survival (if participating in PET Sub-study)
timeFrame: From date of randomisation/registration to death from any cause, assessed for 36 months
measure: Local Failure Free Survival (if participating in PET Sub-study)
timeFrame: From date of randomisation/registration to first local failure event, assessed for 36 months
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Camperdown
country: Australia
facility: Chris O'brien Lifehouse
city: Clayton
country: Australia
facility: Monash Children's Hospital
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
city: Melbourne
country: Australia
facility: Royal Childrens Hospital Melbourne
city: New Lambton Heights
country: Australia
facility: John Hunter Children's Hospital
city: Perth
country: Australia
facility: Perth Children's Hospital
city: Sydney
country: Australia
facility: Sydney Children's Hospital
city: Sydney
country: Australia
facility: The Childrens Hospital At Westmead
city: Westmead
country: Australia
facility: Westmead Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Linz
country: Austria
facility: Kepler University Clinic Linz
city: Vienna
country: Austria
facility: St Anna Childrens Hospital
city: Brussels
country: Belgium
facility: Hopital Universitaire Des Enfants Reine Fabiola
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Uz Leuven Campus Gasthuisberg
city: Liège
country: Belgium
facility: Centre Hospitalier Regional De La Citadelle
city: Liège
country: Belgium
facility: Clinique Chc Montlegia
city: Brno
country: Czechia
facility: Masaryk University Hospital Brno
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: University Hospital Rigshospitalet
city: Angers
country: France
facility: Centre Hospitalier Universitaire D'angers
city: Besançon
country: France
facility: Centre Hospitalier Regional Universitaire Besancon - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire De Bordeaux - Hopital Pellegrin
city: Brest
country: France
facility: Centre Hospitalier Regional Universitaire Brest - Hopital Morvan
city: Caen
country: France
facility: Centre Francois Baclesse
city: Caen
country: France
facility: Centre Hospitalier Universitaire De Caen
city: Dijon
country: France
facility: Centre Hospitalier Universitaire Dijon Bourgogne - Hopital D'enfants
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire De Grenoble
city: La Réunion
country: France
facility: Centre Hospitalier Universitaire La Reunion
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Hopital De La Timone (ap-hm)
city: Nancy
country: France
facility: Centre Hospitalier Universitaire De Nancy
city: Nantes
country: France
facility: Centre Hospitalier Universitaire De Nantes
city: Paris
country: France
facility: Hopital Armand Trousseau
city: Paris
country: France
facility: Institut Curie
city: Pessac
country: France
facility: Centre Hospitalier Universitaire Haut Levque
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire De Poitiers
city: Reims
country: France
facility: Chu De Reims
city: Rennes
country: France
facility: Centre Eugne Marquis De Rennes
city: Rennes
country: France
facility: Centre Hospitalier Universitaire De Rennes - Hopital Pontchaillou
city: Rouen
country: France
facility: Centre Hospitalier Universitaire De Rouen
city: Saint-Étienne
country: France
facility: Centre Hospitalier Universitaire Saint-etienne
city: Strasbourg
country: France
facility: Strasbourg Hautepierre
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire De Toulouse - Hopital Des Enfants
city: Tours
country: France
facility: Centre Hospitalier Regional Universitaire De Tours - Hopital Clocheville
city: Villejuif
country: France
facility: Gustave Roussy
city: Athens
country: Greece
facility: Children's General Hospital P and A Kyriakou
city: Athens
country: Greece
facility: Department of Pediatric Hematology-oncology - Aghia Sophia Children's Hospital
city: Athens
country: Greece
facility: Hellenic Society of Pediatric Hematology- Oncology
city: Athens
country: Greece
facility: University Unit of Pediatric Oncology-hematology - Children's Hospital Agia Sophia
city: Attikí
country: Greece
facility: Children's and Adolescent's Oncology Clinic, "MITERA" Children's Hospital
city: Iraklio
country: Greece
facility: Hematology-oncology Children's Clinic, University General Hospital of Heraklion
city: Thessaloniki
country: Greece
facility: Ippokratio General Hospital of Thessaloniki
city: Thessaloníki
country: Greece
facility: Ahepa University General Hospital of Thessaloniki
city: Crumlin
country: Ireland
facility: Our Lady's Children's Hospital
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah University Medical Centre
city: Petah Tikva
country: Israel
facility: Schneider Medical Centre
city: Tel Aviv
country: Israel
facility: Dana Children's Hospital, Tel Aviv Sourasky Medical Center
city: Tel HaShomer
country: Israel
facility: Chaim Sheba Medical Centre
city: Padova
country: Italy
facility: University Hospital of Padova (azienda Ospedaliera of Padua)
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum Voor Kinderoncologie
city: Auckland
country: New Zealand
facility: Starship Children's Health
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital - Paediatric
city: Oslo
country: Norway
facility: Oslo University Hospital - Paediatrics
city: Oslo
country: Norway
facility: Oslo University Hospital - Radiumhospitalet
city: Tromso
country: Norway
facility: University Hospital of North Norway - Paediatric
city: Trondheim
country: Norway
facility: St Olavs Hospital - Paediatric
city: Lisbon
country: Portugal
facility: Instituto Portugues De Oncologia De Losbona Francisco Gentil, Epe
city: Bratislava
country: Slovakia
facility: Bratislava, National Institute for Children's Diseases
city: Ljubljana
country: Slovenia
facility: University Childrens Hospital Ljubljana
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubjlana
city: Barcelona
country: Spain
facility: Hospital Sant Joan De Deu
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'hebron
city: Bilbao
country: Spain
facility: Hospital De Cruces
city: Madrid
country: Spain
facility: Hospital Del Nino Jesus
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario De Malaga
city: Seville
country: Spain
facility: Hospital Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Politecnico U La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet Materno - infantil
city: Uppsala
country: Sweden
facility: Uppsala University Childrens Hospital
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Basel
country: Switzerland
facility: Universitats-kinderspital Bieder Basel (UKBB)
city: Bellinzona
country: Switzerland
facility: Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Geneva
country: Switzerland
facility: Hug Hopitaux Universitaires De Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne
city: Luzern
country: Switzerland
facility: Luzerner Kantonspital - Kinderspital Luzern
city: St Gallen
country: Switzerland
facility: Ostschweizer Kinderspital
city: Zurich
country: Switzerland
facility: Universitaetsspital Zurich
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Birmingham
country: United Kingdom
facility: The Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology And Oncology Centre
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: Noah's Ark Children's Hospital for Wales
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Children and Young People
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children Glasgow
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: London
country: United Kingdom
facility: Royal Marsden Hospital London
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre, Nottingham
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Cancer Centre
Study officials:
affiliation: Chief Investigator
name: Meriel Jenney
role: PRINCIPAL_INVESTIGATOR
References: