FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma
FaR-RMS
3 other identifiers
interventional
1,672
18 countries
116
Brief Summary
FaR-RMS is an over-arching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2020
Longer than P75 for phase_1
116 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 22, 2019
CompletedStudy Start
First participant enrolled
September 17, 2020
CompletedFirst Posted
Study publicly available on registry
November 12, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2030
May 23, 2024
May 1, 2024
9.7 years
November 22, 2019
May 22, 2024
Conditions
Outcome Measures
Primary Outcomes (8)
Event Free Survival (RT2)
Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm
From randomisation to first failure event, timeframe 36 months
Event Free Survival (CT1A)
Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm
From randomisation to first failure event, timeframe 36 months
Event Free Survival (CT1B)
Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm
From randomisation to first failure event, timeframe 36 months
Event Free Survival (CT2A)
Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm
From randomisation to first failure event, timeframe 36 months
Event Free Survival (CT2B)
Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm
Time from randomisation to first failure event, timeframe 36 months
Event Free Survival (CT3)
To determine whether new systemic therapy regimens improve event free survival in relapsed RMS compared to standard therapy (VIRT) (CT3): Initial new systemic therapy combination to be tested: o Regorafenib (R) added to vincristine and irinotecan (VIR) (VIRR)
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.
Local Failure Free Survival (RT1A and RT1B)
A local failure event is relapse or progression of tumour at the primary site at any time even if there has been a prior /concurrent, regional or distant failure
Time from randomisation to first local failure event, timeframe 36 months
Local Failure Free Survival (RT1C)
A local failure event is relapse or progression of tumour at the primary site at any time even if there has been a prior /concurrent, regional or distant failure
Time from randomisation to first local failure event, timeframe 36 months
Secondary Outcomes (28)
Recommended Phase II Dose (Phase 1b)
From first patient first visit in dose finding study until appropriate dose level found, estimated 9 months
Maximum Tolerated Dose (Phase 1b)
From first patient first visit in dose finding study until appropriate dose level
Toxicity (All chemotherapy randomisations)
From date of protocol defined treatment until 30 days after the administration of the last treatment
Dose Limiting Toxicity (Phase 1b)
From commencement of treatment until 21 days after the start of cycle 2 (each cycle is 21 days)
Response (Phase 1b, CT1A, CT1B)
Response assessed after course 3 (63 days) and 6 (126 days)
- +23 more secondary outcomes
Study Arms (19)
Phase 1b Dose finding: VHR induction - IRIVA
EXPERIMENTALIrinotecan: an i.v. infusion over 1 hour on days 8,9,10,11 and 12 . For the phase 1b registration, starting dose of 20 mg/m2. Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 as an As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on days 1 and 8 on cycles 3-9. Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.
CT1A: VHR induction - IVADO
ACTIVE COMPARATORIfosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on day 1 on cycles 3-9. Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1. Doxorubicin: 30 mg/m2 as an i.v infusion over 1 hour on days 1 and 2 on cycles 1-4
CT1A: VHR Induction IRIVA
EXPERIMENTALIrinotecan: an i.v. infusion over 1 hour on days 8,9,10,11 and 12 . Phase 2 recommended dose as determined by IRIVA dose finding arm Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on days 1 and 8 on cycles 3-9. Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.
CT1B: HR Induction IVA
ACTIVE COMPARATORIfosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on day 1 on cycles 3-9. Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.
CT1B: HR Induction IRIVA
EXPERIMENTALIrinotecan: an i.v. infusion over 1 hour on days 8,9,10,11 and 12 . Phase 2 recommended dose as determined by IRIVA dose finding arm Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on days 1 and 8 on cycles 3-9. Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.
RT1A: Preoperative Radiotherapy
EXPERIMENTALTo be given either 41.4 Gy or 50.4 Gy prior to surgery
RT1A: Post operative radiotherapy
ACTIVE COMPARATORTo be given either 41.4 Gy or 50.4 Gy following surgery
RT1B: Radiotherapy for resectable disease: dose escalated
EXPERIMENTALTo receive 50.4 Gy
RT1B: Radiotherapy for resectable disease: standard dose
ACTIVE COMPARATORTo receive 41.4 Gy
RT1C: Radiotherapy for unresectable disease: dose escalated
EXPERIMENTALTo receive 59.4 Gy
RT1C: Radiotherapy for unresectable disease: standard dose
ACTIVE COMPARATORTo receive 50.4 Gy
RT2: Radiotherapy to primary tumour and involved lymph nodes
EXPERIMENTALRadiotherapy to the primary tumour and involved regional lymph nodes only
RT2: Radiotherapy to all metastatic sites
EXPERIMENTALRadiotherapy given to all metastatic sites
CT2A: VHR Maintenance - VC
EXPERIMENTALVinorelbine: 25 mg/m2 i.v. or 60 mg/m2 orally on days 1,8 and 15 Cyclophosphamide 25 mg/m2 orally daily for 28 days
CT2A: Maintenance -Stop treatment
NO INTERVENTIONTo stop treatment at the point of randomisation
CT2B: HR Maintenance - VC
EXPERIMENTALVinorelbine: 25 mg/m2 i.v. on days 1,8 and 15 Cyclophosphamide 25 mg/m2 orally daily for 28 days
CT2B: HR Maintenance - Stop Treatment
NO INTERVENTIONTo stop treatment at the point of randomisation
CT3: Relpased Chemotherapy - VIRT
ACTIVE COMPARATORVincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg) on days 1 and 8 Irinotecan: 50 mg/m2 as an i.v. infusion over 1 hour on days 1-5 Temozolomide: 125 mg/m2 (Escalate to 150mg/m2/day in Cycle 2 if no toxicity \> grade 3) as an oral tablets prior to vincristine and irinotecan on days 1-5
CT3: Relapsed Chemotherapy - VIRR
EXPERIMENTALVincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg) on days 1 and 8 Irinotecan: 50 mg/m2 as an i.v. infusion over 1 hour on days 1-5 Regorafenib: Children between 6 and 24 months = 65 mg/m2, children less than 12 and/or less than 40kg dose = 82 mg/m2 Maximum 120 mg, Fixed dose of 120 mg for patients over 12 years of age AND ≥ 40 kg, as an oral tablets on days 8 to 21.
Interventions
antineoplastic enzyme inhibitor
Antineoplastic agent that is a polypeptide antibiotic
An anthracycline topoisomerase inhibitor isolated from streptpmyces peucetius var. casesius
chemotherapeutic agent chemically related to the nitrogen mustards and is a synthetic analog of cyclophosphamide
anti neoplastic vinca alkaloid agent
vinca alkaloid with a role as an antineoplastic agent
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent
Ionising radiation
Oral multi-kinase inhibitor that targets a broad range of angiogenic, stromal and oncogenic kinases, including vascular endothelial growth factor receptors (VEFGR) 1, 2 and 3, tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (TIE2), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR), c-KIT, RET, RAF-1 and BRAF (wild-type and V600E mutant).
Eligibility Criteria
You may qualify if:
- Histologically confirmed diagnosis of RMS (except pleomorphic RMS)
- Written informed consent from the patient and/or the parent/legal guardian
- Entered in to the FaR-RMS study at diagnosis
- Very High Risk disease
- Age \>12 months and ≤25 years
- No prior treatment for RMS other than surgery
- Medically fit to receive treatment
- Adequate hepatic function:
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age, unless the patient is known to have Gilbert's syndrome
- ALT or AST \< 2.5 X ULN for age
- Absolute neutrophil count ≥1.0x 109/L
- Platelets ≥ 80 x 109/L
- Adequate renal function: estimated or measured creatinine clearance ≥60 ml/min/1.73 m2
- Documented negative pregnancy test for female patients of childbearing potential
- 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
- +1 more criteria
You may not qualify if:
- Weight \<10kg
- Active \> grade 2 diarrhoea
- Prior allo- or autologous Stem Cell Transplant
- Uncontrolled inter-current illness or active infection
- Pre-existing medical condition precluding treatment
- Urinary outflow obstruction that cannot be relieved prior to starting treatment
- Active inflammation of the urinary bladder (cystitis)
- Known hypersensitivity to any of the treatments or excipients
- Second malignancy
- Pregnant or breastfeeding women
- Entered in to the FaR-RMS study at diagnosis
- Very High Risk disease
- Age ≥ 6 months
- Available for randomisation ≤60 days after diagnostic biopsy/surgery
- No prior treatment for RMS other than surgery
- +131 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (128)
Queensland Children's Hospital
Brisbane, 4101, Australia
Chris O'brien Lifehouse
Camperdown, Australia
Monash Children's Hospital
Clayton, Australia
Peter Maccallum Cancer Centre
Melbourne, Australia
Royal Childrens Hospital Melbourne
Melbourne, Australia
John Hunter Children's Hospital
New Lambton Heights, 2310, Australia
Perth Children's Hospital
Perth, Australia
Sydney Children's Hospital
Sydney, Australia
The Childrens Hospital At Westmead
Sydney, Australia
Westmead Hospital
Westmead, Australia
Princess Alexandra Hospital
Woolloongabba, Australia
Kepler University Clinic Linz
Linz, Austria
St Anna Childrens Hospital
Vienna, Austria
Cliniques Universitaires Saint Luc
Brussels, Belgium
Hopital Universitaire Des Enfants Reine Fabiola
Brussels, Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium
Uz Leuven Campus Gasthuisberg
Leuven, Belgium
Centre Hospitalier Regional De La Citadelle
Liège, Belgium
Clinique Chc Montlegia
Liège, Belgium
Masaryk University Hospital Brno
Brno, 625 00, Czechia
Aarhus University Hospital
Aarhus, Denmark
University Hospital Rigshospitalet
Copenhagen, Denmark
Centre Hospitalier Universitaire D'angers
Angers, France
Centre Hospitalier Regional Universitaire Besancon - Hopital Jean Minjoz
Besançon, France
Centre Hospitalier Universitaire De Bordeaux - Hopital Pellegrin
Bordeaux, France
Centre Hospitalier Regional Universitaire Brest - Hopital Morvan
Brest, France
Centre Francois Baclesse
Caen, France
Centre Hospitalier Universitaire De Caen
Caen, France
Centre Hospitalier Universitaire Dijon Bourgogne - Hopital D'enfants
Dijon, France
Centre Hospitalier Universitaire De Grenoble
Grenoble, France
Centre Hospitalier Universitaire La Reunion
La Réunion, France
Centre Oscar Lambret
Lille, France
Centre Leon Berard
Lyon, France
Hopital De La Timone (ap-hm)
Marseille, France
Centre Hospitalier Universitaire De Nancy
Nancy, France
Centre Hospitalier Universitaire De Nantes
Nantes, France
Hopital Armand Trousseau
Paris, France
Institut Curie
Paris, France
Centre Hospitalier Universitaire Haut Levque
Pessac, France
Centre Hospitalier Universitaire De Poitiers
Poitiers, France
Chu De Reims
Reims, France
Centre Eugne Marquis De Rennes
Rennes, France
Centre Hospitalier Universitaire De Rennes - Hopital Pontchaillou
Rennes, France
Centre Hospitalier Universitaire De Rouen
Rouen, France
Centre Hospitalier Universitaire Saint-etienne
Saint-Etienne, France
Strasbourg Hautepierre
Strasbourg, France
Centre Hospitalier Universitaire De Toulouse - Hopital Des Enfants
Toulouse, France
Centre Hospitalier Regional Universitaire De Tours - Hopital Clocheville
Tours, France
Gustave Roussy
Villejuif, 94805, France
Children's General Hospital P and A Kyriakou
Athens, 115 27, Greece
Department of Pediatric Hematology-oncology - Aghia Sophia Children's Hospital
Athens, Greece
Hellenic Society of Pediatric Hematology- Oncology
Athens, Greece
University Unit of Pediatric Oncology-hematology - Children's Hospital Agia Sophia
Athens, Greece
Children's and Adolescent's Oncology Clinic, "MITERA" Children's Hospital
Attiki, 151 23, Greece
Hematology-oncology Children's Clinic, University General Hospital of Heraklion
Heraklion, 715 00, Greece
Ahepa University General Hospital of Thessaloniki
Thessaloniki, Greece
Ippokratio General Hospital of Thessaloniki
Thessaloniki, Greece
Our Lady's Children's Hospital
Crumlin, Ireland
Rambam Health Care Campus
Haifa, Israel
Hadassah University Medical Centre
Jerusalem, Israel
Schneider Medical Centre
Petah Tikva, Israel
Dana Children's Hospital, Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Chaim Sheba Medical Centre
Tel Litwinsky, Israel
University Hospital of Padova (azienda Ospedaliera of Padua)
Padua, Italy
University Medical Centre Groningen
Groningen, Netherlands
Prinses Maxima Centrum Voor Kinderoncologie
Utrecht, Netherlands
Starship Children's Health
Auckland, New Zealand
Christchurch Hospital
Christchurch, New Zealand
Haukeland University Hospital - Paediatric
Bergen, Norway
Oslo University Hospital - Paediatrics
Oslo, Norway
Oslo University Hospital - Radiumhospitalet
Oslo, Norway
University Hospital of North Norway - Paediatric
Tromsø, Norway
St Olavs Hospital - Paediatric
Trondheim, Norway
Instituto Portugues De Oncologia De Losbona Francisco Gentil, Epe
Lisbon, Portugal
Bratislava, National Institute for Children's Diseases
Bratislava, Slovakia
University Childrens Hospital Ljubljana
Ljubljana, Slovenia
University Medical Centre Ljubjlana
Ljubljana, Slovenia
Hospital Sant Joan De Deu
Barcelona, Spain
Hospital Universitari Vall D'hebron
Barcelona, Spain
Hospital De Cruces
Bilbao, 48903, Spain
Hospital Del Nino Jesus
Madrid, 28009, Spain
Hospital Universitario Gregorio Maranon
Madrid, 28009, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Regional Universitario De Malaga
Málaga, Spain
Hospital Virgen Del Rocio
Seville, Spain
Hospital Politecnico U La Fe
Valencia, 46026, Spain
Hospital Universitario Miguel Servet Materno - infantil
Zaragoza, Spain
Uppsala University Childrens Hospital
Uppsala, Sweden
Kantonsspital Aarau
Aarau, Switzerland
Universitats-kinderspital Bieder Basel (UKBB)
Basel, Switzerland
Ospedale San Giovanni
Bellinzona, Switzerland
Inselspital Bern
Bern, Switzerland
Hug Hopitaux Universitaires De Geneve
Geneva, Switzerland
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne
Lausanne, Switzerland
Luzerner Kantonspital - Kinderspital Luzern
Lucerne, Switzerland
Ostschweizer Kinderspital
Sankt Gallen, Switzerland
Universitaetsspital Zurich
Zurich, Switzerland
Royal Marsden Hospital
Sutton, Surrey, SM2 5PT, United Kingdom
Royal Aberdeen Children's Hospital
Aberdeen, United Kingdom
Belfast City Hospital
Belfast, United Kingdom
Royal Belfast Hospital for Sick Children
Belfast, United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom
The Queen Elizabeth Hospital
Birmingham, United Kingdom
Bristol Haematology And Oncology Centre
Bristol, United Kingdom
Bristol Royal Hospital for Children
Bristol, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
Noah's Ark Children's Hospital for Wales
Cardiff, United Kingdom
Velindre Hospital
Cardiff, United Kingdom
Royal Hospital for Children and Young People
Edinburgh, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Royal Hospital for Children Glasgow
Glasgow, United Kingdom
Leeds General Infirmary
Leeds, United Kingdom
St James's University Hospital
Leeds, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Alder Hey Children's Hospital
Liverpool, United Kingdom
Great Ormond Street Hospital for Children
London, United Kingdom
Royal Marsden Hospital London
London, United Kingdom
University College London Hospital
London, United Kingdom
Royal Manchester Children's Hospital
Manchester, M13 9WL, United Kingdom
Christie Hospital
Manchester, United Kingdom
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne, United Kingdom
Nottingham City Hospital
Nottingham, United Kingdom
Queen's Medical Centre, Nottingham
Nottingham, United Kingdom
John Radcliffe Hospital
Oxford, United Kingdom
Sheffield Children's Hospital
Sheffield, United Kingdom
Weston Park Hospital
Sheffield, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Meriel Jenney
Chief Investigator
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 22, 2019
First Posted
November 12, 2020
Study Start
September 17, 2020
Primary Completion (Estimated)
June 1, 2030
Study Completion (Estimated)
June 1, 2030
Last Updated
May 23, 2024
Record last verified: 2024-05