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RhabdomyosarcomaPhase 1/2FaR-RMSNCT04625907

FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma

A Phase 1/2 study testing Irinotecan, Actinomycin D and Doxorubicin in people with Rhabdomyosarcoma, run by University of Birmingham at 128 sites in 20 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

FaR-RMS is an over-arching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS) Read more about this study

Who is it for?
Any age
Conditions the study is for
Rhabdomyosarcoma
What is being tested?
Irinotecan, Actinomycin D and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,672 participants
Where
128 sitesin 20 countries
Study dates
17 Sep 2020to Jun 2030
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
  • First or subsequent relapse of histologically verified RMS
  • Age ≥ 6 months
  • Measurable or evaluable disease
  • No cytotoxic chemotherapy or other investigational medicinal product (IMP) within previous three weeks: within two weeks for vinorelbine and cyclophosphamide maintenance chemotherapy
  • Medically fit to receive trial treatment
Show all 9Show fewer
  • Documented negative pregnancy test for female patients of childbearing potential within 7 days of planned randomisation
  • 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
  • Written informed consent from the patient and/or the parent/legal guardian

Who cannot join

  • 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
Show all 146Show fewer
  • Active inflammation of the urinary bladder (cystitis)
  • Known hypersensitivity to any of the treatments or excipients
  • Second malignancy
  • Pregnant or breastfeeding women
  • Frontline chemotherapy randomisation Very High Risk - CT1a Inclusion
  • 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
  • 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
  • Absolute neutrophil count ≥1.0x 109/L (except in patients with documented bone marrow disease)
  • Platelets ≥ 80 x 109/L (except in patients with documented bone marrow disease)
  • Fractional Shortening ≥ 28%
  • 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
  • Written informed consent from the patient and/or the parent/legal guardian
  • 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
  • Frontline chemotherapy randomisation High Risk - CT1b Inclusion
  • Entered in to the FaR-RMS study at diagnosis
  • High Risk disease
  • Age ≥ 6 months
  • Available for randomisation ≤60 days after diagnostic biopsy/surgery
  • 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, except if the patient is known to have Gilbert's syndrome
  • Absolute neutrophil count ≥1.0x 109/L
  • Platelets ≥ 80 x 109/L
  • 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
  • Written informed consent from the patient and/or the parent/legal guardian
  • 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
  • Frontline Radiotherapy Note: eligible patients may enter multiple radiotherapy randomisations.
  • Radiotherapy Inclusion - for all radiotherapy randomisations
  • Entered in to the FaR-RMS study (at diagnosis or prior to radiotherapy randomisation)
  • Very High Risk, High Risk and Standard Risk disease
  • ≥ 2 years of age
  • 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
  • Patient assessed as medically fit to receive the radiotherapy
  • 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
  • Written informed consent from the patient and/or the parent/legal guardian
  • Radiotherapy Exclusion - for all radiotherapy randomisations
  • Prior allo- or autologous Stem Cell Transplant
  • Second malignancy
  • Pregnant or breastfeeding women
  • Receiving radiotherapy as brachytherapy
  • RT1a Specific Inclusion
  • Primary tumour deemed resectable (predicted R0/ R1 resection feasible) after 3 cycles of induction chemotherapy (6 cycles for metastatic disease)
  • Adjuvant radiotherapy required in addition to surgical resection (local decision).
  • 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
  • Primary tumour deemed resectable (predicted R0/R1 resection) after 3 cycles of induction chemotherapy (6 cycles for metastatic disease).
  • Adjuvant radiotherapy required in addition to surgical resection (local decision)
  • Higher Local Failure Risk (HLFR) based on presence of either of the following criteria:
  • Unfavourable site
  • Age ≥ 18yrs
  • 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
  • Primary radiotherapy indicated (local decision)
  • Higher Local Failure Risk (HLFR) based on either of the following criteria:
  • Unfavourable site
  • Age ≥ 18yrs
  • 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
  • Available for randomisation after cycle 6 and before the start of cycle 9 of induction chemotherapy.
  • 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.
  • Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
  • Very High Risk disease
  • Received frontline induction chemotherapy as part of the FaR-RMS trial or with a IVA/IVADo based chemotherapy regimen
  • Patients for whom ifosfamide has been replaced with cyclophosphamide will be eligible
  • Completed 11 cycles of VnC maintenance treatment (either oral or IV regimens)
  • No evidence of progressive disease
  • Absence of severe vincristine neuropathy - i.e requiring discontinuation of vincristine treatment)
  • Medically fit to continue to receive treatment
  • 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
  • Written informed consent from the patient and/or the parent/legal guardian
  • Prior allo- or autologous Stem Cell Transplant
  • Uncontrolled intercurrent illness or active infection
  • Urinary outflow obstruction that cannot be relieved prior to starting treatment
  • Active inflammation of the urinary bladder (cystitis)
  • Second malignancy
  • Pregnant or breastfeeding women
  • Maintenance chemotherapy (High Risk) - CT2b Randomisation must take place during the 6th cycle of maintenance chemotherapy. Inclusion
  • Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
  • High Risk disease
  • 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
  • Completed 5 cycles of VnC maintenance treatment
  • No evidence of progressive disease
  • Absence of severe vincristine neuropathy i.e. requiring discontinuation of vincristine treatment
  • Medically fit to continue to receive treatment
  • 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
  • Written informed consent from the patient and/or the parent/legal guardian
  • Prior allo- or autologous Stem Cell Transplant
  • Uncontrolled inter current illness or active infection
  • Urinary outflow obstruction that cannot be relieved prior to starting treatment
  • Active inflammation of the urinary bladder (cystitis)
  • Second malignancy
  • Pregnant or breastfeeding women
  • CT3 Relapsed Chemotherapy
  • Progression during frontline therapy without previous response (=Refractory to first line treatment)
  • Prior regorafenib or temozolomide
  • Active > grade 1 diarrhoea
  • ALT or AST >3.0 x upper limit normal (ULN)
  • Bilirubin, Total >1.5 x ULN; total bilirubin is allowed up to 3 x ULN if Gilbert's syndrome is documented
  • 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)
  • Uncontrolled hypertension > 95th centile for age and gender
  • Prior allo- or autologous Stem Cell Transplant
  • Uncontrolled inter-current illness or active infection
  • Pre-existing medical condition precluding treatment
  • Known hypersensitivity to any of the treatments or excipients
  • Second malignancy
  • Pregnant or breastfeeding women

Trial locations and contacts

128 sites in 20 countries. Contact the study team or a site near you to ask about taking part.

Bridget Shaw contact

0121 414 2996

farrms@trials.bham.ac.uk

Emma Gray contact

0121 414 3799

farrms@trials.bham.ac.uk

128 sites in 20 countries

United Kingdom31 sites, 31 recruiting

  • Royal Aberdeen Children's Hospital

    Aberdeen

    Hugh Bishop

    Recruiting

  • Belfast City Hospital

    Belfast

    Robert Johnston

    Not yet recruiting

  • Royal Belfast Hospital for Sick Children

    Belfast

    Robert Johnston

    Not yet recruiting

  • Birmingham Children's Hospital

    Birmingham

    Susanne Gatz

    Recruiting

  • The Queen Elizabeth Hospital

    Birmingham

    Mariam Jafri

    Not yet recruiting

  • Bristol Haematology And Oncology Centre

    Bristol

    Helen Rees

    Recruiting

  • Bristol Royal Hospital for Children

    Bristol

    Helen Rees

    Recruiting

  • Addenbrooke's Hospital

    Cambridge

    James Nicholson

    Recruiting

  • Noah's Ark Children's Hospital for Wales

    Cardiff

    Meriel Jenney

    Recruiting

  • Velindre Hospital

    Cardiff

    D W Owen Tilsley

    Recruiting

  • Royal Hospital for Children and Young People

    Edinburgh

    Angela Jesudason

    Recruiting

  • Beatson West of Scotland Cancer Centre

    Glasgow

    Fiona Cowie

    Recruiting

  • Royal Hospital for Children Glasgow

    Glasgow

    Milind Ronghe

    Recruiting

  • Leeds General Infirmary

    Leeds

    Christopher Lethaby

    Recruiting

  • St James's University Hospital

    Leeds

    Christopher Lethaby

    Recruiting

  • Leicester Royal Infirmary

    Leicester

    Emma Ross

    Recruiting

  • Alder Hey Children's Hospital

    Liverpool

    Kate Cooper

    Recruiting

  • Great Ormond Street Hospital for Children

    London

    Olga Slater

    Recruiting

  • Royal Marsden Hospital London

    London

    J Chisholm

    Recruiting

  • University College London Hospital

    London

    Maria Michelagnoli

    Recruiting

  • Royal Manchester Children's Hospital

    Manchester, M13 9WL

    Bernadette Brennan, 0161 701 8424

    Recruiting

  • Christie Hospital

    Manchester

    Martin McCabe

    Recruiting

  • Clatterbridge Cancer Centre

    Metropolitan Borough of Wirral

    S Nasim Ali

    Recruiting

  • Royal Victoria Infirmary

    Newcastle upon Tyne

    Quentin Campbell-Hewson

    Recruiting

  • Nottingham City Hospital

    Nottingham

    Ivo Hennig

    Recruiting

  • Queen's Medical Centre, Nottingham

    Nottingham

    Jennifer Turnbull

    Recruiting

  • John Radcliffe Hospital

    Oxford

    Esther Blanco

    Recruiting

  • Sheffield Children's Hospital

    Sheffield

    Anna Jenkins

    Recruiting

  • Weston Park Hospital

    Sheffield

    Robin Young

    Not yet recruiting

  • Southampton General Hospital

    Southampton

    Jessica Bate

    Recruiting

  • Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

    Julia Chisholm, 020 8642 6011

    Recruiting

Other trials in United Kingdom

France27 sites, 27 recruiting

  • Centre Hospitalier Universitaire D'angers

    Angers

    S Proust

    Recruiting

  • Centre Hospitalier Regional Universitaire Besancon - Hopital Jean Minjoz

    Besançon

    S Klein

    Recruiting

  • Centre Hospitalier Universitaire De Bordeaux - Hopital Pellegrin

    Bordeaux

    C Verite

    Recruiting

  • Centre Hospitalier Regional Universitaire Brest - Hopital Morvan

    Brest

    L Carausu

    Recruiting

  • Centre Francois Baclesse

    Caen

    F Missohou

    Recruiting

  • Centre Hospitalier Universitaire De Caen

    Caen

    D Bodet

    Recruiting

  • Centre Hospitalier Universitaire Dijon Bourgogne - Hopital D'enfants

    Dijon

    C Briandet

    Recruiting

  • Centre Hospitalier Universitaire De Grenoble

    Grenoble

    D Plantaz

    Recruiting

  • Centre Hospitalier Universitaire La Reunion

    La Réunion

    Y Reguerre

    Recruiting

  • Centre Oscar Lambret

    Lille

    A Defachelles

    Recruiting

  • Centre Leon Berard

    Lyon

    N Corradini

    Recruiting

  • Hopital De La Timone (ap-hm)

    Marseille

    A Rome

    Recruiting

  • Centre Hospitalier Universitaire De Nancy

    Nancy

    L Mansuy

    Recruiting

  • Centre Hospitalier Universitaire De Nantes

    Nantes

    M Cleirec

    Recruiting

  • Hopital Armand Trousseau

    Paris

    H Boutroux

    Recruiting

  • Institut Curie

    Paris

    D Orbach

    Recruiting

  • Centre Hospitalier Universitaire Haut Levque

    Pessac

    A Huchet

    Recruiting

  • Centre Hospitalier Universitaire De Poitiers

    Poitiers

    F Millot

    Recruiting

  • Chu De Reims

    Reims

    C Pluchart

    Recruiting

  • Centre Eugne Marquis De Rennes

    Rennes

    J Leseur

    Recruiting

  • Centre Hospitalier Universitaire De Rennes - Hopital Pontchaillou

    Rennes

    S Taque

    Recruiting

  • Centre Hospitalier Universitaire De Rouen

    Rouen

    A Marie Cardine

    Recruiting

  • Centre Hospitalier Universitaire Saint-etienne

    Saint-Etienne

    C Berger

    Recruiting

  • Strasbourg Hautepierre

    Strasbourg

    S Jannier

    Recruiting

  • Centre Hospitalier Universitaire De Toulouse - Hopital Des Enfants

    Toulouse

    MP Castex

    Recruiting

  • Centre Hospitalier Regional Universitaire De Tours - Hopital Clocheville

    Tours

    J Serre

    Recruiting

  • Gustave Roussy

    Villejuif, 94805

    Veronique Minard-Colin

    Recruiting

Other trials in France

Australia11 sites, 11 recruiting

  • Queensland Children's Hospital

    Brisbane, 4101

    R Walker

    Recruiting

  • Chris O'brien Lifehouse

    Camperdown

    Angela Hong

    Recruiting

  • Monash Children's Hospital

    Clayton

    Paul Wood

    Recruiting

  • Peter Maccallum Cancer Centre

    Melbourne

    Jeremy Lewin

    Recruiting

  • Royal Childrens Hospital Melbourne

    Melbourne

    Marty Campbell

    Recruiting

  • John Hunter Children's Hospital

    New Lambton Heights, 2310

    E Hesketh

    Recruiting

  • Perth Children's Hospital

    Perth

    Marianne Phillips

    Recruiting

  • Sydney Children's Hospital

    Sydney

    Timothy Trahair

    Recruiting

  • The Childrens Hospital At Westmead

    Sydney

    Jessica Ryan

    Recruiting

  • Westmead Hospital

    Westmead

    Jennifer Chard

    Recruiting

  • Princess Alexandra Hospital

    Woolloongabba

    Rick Walker

    Recruiting

Other trials in Australia

Spain10 sites, 10 recruiting

  • Hospital Sant Joan De Deu

    Barcelona

    Moira Garraus Oneca

    Recruiting

  • Hospital Universitari Vall D'hebron

    Barcelona

    Raquel Hladun Alvaro

    Recruiting

  • Hospital De Cruces

    Bilbao, 48903

    Ricardo Lopez Almaraz

    Recruiting

  • Hospital Del Nino Jesus

    Madrid, 28009

    David Ruano

    Recruiting

  • Hospital Universitario Gregorio Maranon

    Madrid, 28009

    Cristina Mata

    Recruiting

  • Hospital Universitario La Paz

    Madrid

    Pedro Rubio

    Recruiting

  • Hospital Regional Universitario De Malaga

    Málaga

    Guiomar Gutierrez Schiaffino

    Recruiting

  • Hospital Virgen Del Rocio

    Seville

    Gema Ramirez Villar

    Recruiting

  • Hospital Politecnico U La Fe

    Valencia, 46026

    Antonio Juan Ribelles

    Recruiting

  • Hospital Universitario Miguel Servet Materno - infantil

    Zaragoza

    Ascensión Muñoz

    Recruiting

Other trials in Spain

Switzerland9 sites, 9 recruiting

  • Kantonsspital Aarau

    Aarau

    Andreas Klein-Franke

    Recruiting

  • Universitats-kinderspital Bieder Basel (UKBB)

    Basel

    Nicolas von der Weld

    Recruiting

  • Ospedale San Giovanni

    Bellinzona

    Pierluigi Brazzola

    Recruiting

  • Inselspital Bern

    Bern

    Jochen Roessler

    Recruiting

  • Hug Hopitaux Universitaires De Geneve

    Geneva

    Andre Von Buren

    Recruiting

  • Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne

    Lausanne

    Manuel Diezi

    Recruiting

  • Luzerner Kantonspital - Kinderspital Luzern

    Lucerne

    Freimut Schilling

    Recruiting

  • Ostschweizer Kinderspital

    Sankt Gallen

    Jeanette Greiner

    Recruiting

  • Universitaetsspital Zurich

    Zurich

    Willemijn Breunis

    Recruiting

Other trials in Switzerland

Greece8 sites, 8 recruiting

  • Children's General Hospital P and A Kyriakou

    Athens, 115 27

    Marina Servitzoglou

    Recruiting

  • Department of Pediatric Hematology-oncology - Aghia Sophia Children's Hospital

    Athens

    Vasiliki Tzotzola

    Recruiting

  • Hellenic Society of Pediatric Hematology- Oncology

    Athens

    Apostolos Pourtsidis

    Recruiting

  • University Unit of Pediatric Oncology-hematology - Children's Hospital Agia Sophia

    Athens

    Antonis Kattamis

    Recruiting

  • Children's and Adolescent's Oncology Clinic, "MITERA" Children's Hospital

    Attiki, 151 23

    Apostolos Pourtsidis

    Recruiting

  • Hematology-oncology Children's Clinic, University General Hospital of Heraklion

    Heraklion, 715 00

    Nikolaos Katzilakis

    Recruiting

  • Ahepa University General Hospital of Thessaloniki

    Thessaloniki

    Emmanouil Chatzipantelis

    Recruiting

  • Ippokratio General Hospital of Thessaloniki

    Thessaloniki

    Evgenia Papakonstantinou

    Recruiting

Other trials in Greece

Belgium6 sites, 6 recruiting

  • Cliniques Universitaires Saint Luc

    Brussels

    B Brichard

    Recruiting

  • Hopital Universitaire Des Enfants Reine Fabiola

    Brussels

    Christine Devalck

    Recruiting

  • Universitair Ziekenhuis Gent

    Ghent

    C Dhooge

    Recruiting

  • Uz Leuven Campus Gasthuisberg

    Leuven

    M Renard

    Recruiting

  • Centre Hospitalier Regional De La Citadelle

    Liège

    S Gatineau-Sailliant

    Recruiting

  • Clinique Chc Montlegia

    Liège

    L Roufiange

    Recruiting

Other trials in Belgium

Israel5 sites, 5 recruiting

  • Rambam Health Care Campus

    Haifa

    Shifra Ash

    Recruiting

  • Hadassah University Medical Centre

    Jerusalem

    Dror Raviv

    Recruiting

  • Schneider Medical Centre

    Petah Tikva

    Shira Amar

    Recruiting

  • Dana Children's Hospital, Tel Aviv Sourasky Medical Center

    Tel Aviv

    Dror Levin

    Recruiting

  • Chaim Sheba Medical Centre

    Tel HaShomer

    Iris Kvenstel

    Recruiting

Other trials in Israel

Norway5 sites, 5 recruiting

  • Haukeland University Hospital - Paediatric

    Bergen

    Ingrid Kristin Torsvik

    Recruiting

  • Oslo University Hospital - Paediatrics

    Oslo

    Heidi Glosli

    Recruiting

  • Oslo University Hospital - Radiumhospitalet

    Oslo

    Kjetil Boye

    Recruiting

  • University Hospital of North Norway - Paediatric

    Tromsø

    Tove Anita Nystad

    Recruiting

  • St Olavs Hospital - Paediatric

    Trondheim

    Bendik Lund

    Recruiting

Other trials in Norway

Austria2 sites, 2 recruiting

  • Kepler University Clinic Linz

    Linz

    B Aistleitner

    B Aistleitner

    Recruiting

  • St Anna Childrens Hospital

    Vienna

    Ruth Ladenstein

    Recruiting

Other trials in Austria

Denmark2 sites, 2 recruiting

  • Aarhus University Hospital

    Aarhus

    Pernille Wendtland

    Recruiting

  • University Hospital Rigshospitalet

    Copenhagen

    Lisa Hjalgrim

    Recruiting

Other trials in Denmark

Netherlands2 sites, 2 recruiting

  • University Medical Centre Groningen

    Groningen

    Wim Tissing

    Recruiting

  • Prinses Maxima Centrum Voor Kinderoncologie

    Utrecht

    Hans Merks

    Recruiting

Other trials in Netherlands

New Zealand2 sites, 2 recruiting

  • Starship Children's Health

    Auckland

    Mandy De Silva

    Recruiting

  • Christchurch Hospital

    Christchurch

    Tristan Pettitt

    Recruiting

Other trials in New Zealand

Slovenia2 sites, 2 recruiting

  • University Childrens Hospital Ljubljana

    Ljubljana

    Maja Cesen Mazic

    Recruiting

  • University Medical Centre Ljubjlana

    Ljubljana

    Cesen Mazic

    Recruiting

Other trials in Slovenia

Czechia1 site, 1 recruiting

  • Masaryk University Hospital Brno

    Brno, 625 00

    Peter Mudry

    Recruiting

Other trials in Czechia

Ireland1 site, 1 recruiting

  • Our Lady's Children's Hospital

    Crumlin

    Cormac Owens

    Not yet recruiting

Other trials in Ireland

Italy1 site, 1 recruiting

  • University Hospital of Padova (azienda Ospedaliera of Padua)

    Padova

    Gianni Bisogno

    Not yet recruiting

Other trials in Italy

Portugal1 site, 1 recruiting

  • Instituto Portugues De Oncologia De Losbona Francisco Gentil, Epe

    Lisbon

    Cristina Mendes

    Not yet recruiting

Other trials in Portugal

Slovakia1 site, 1 recruiting

  • Bratislava, National Institute for Children's Diseases

    Bratislava

    Martina Mileskova

    Not yet recruiting

Other trials in Slovakia

Sweden1 site, 1 recruiting

  • Uppsala University Childrens Hospital

    Uppsala

    G Ljungman

    Recruiting

Other trials in Sweden

About this study

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

Read the 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.

Being tested
Irinotecan, Actinomycin D, Doxorubicin, Ifosfamide, Vincristine
Medical subject headings
Rhabdomyosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IrinotecanDrug

    antineoplastic enzyme inhibitor

  • Actinomycin DDrug

    Also called Dactinomycin

    Antineoplastic agent that is a polypeptide antibiotic

  • DoxorubicinDrug

    An anthracycline topoisomerase inhibitor isolated from streptpmyces peucetius var. casesius

  • IfosfamideDrug

    chemotherapeutic agent chemically related to the nitrogen mustards and is a synthetic analog of cyclophosphamide

  • VincristineDrug

    anti neoplastic vinca alkaloid agent

  • VinorelbineDrug

    vinca alkaloid with a role as an antineoplastic agent

  • CyclophosphamideDrug

    Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent

  • TemozolomideDrug

    oral antineoplastic alkylating agent

  • radiotherapyRadiation

    Ionising radiation

  • RegorafenibDrug

    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).

Study groups in NCT04625907
Study groupRoleWhat they receive
Phase 1b Dose finding: VHR induction - IRIVAExperimentalIrinotecan: 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.
Receives: Drug: Irinotecan; Drug: Actinomycin D; Drug: Ifosfamide; Drug: Vincristine
CT1A: VHR induction - IVADOActive 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
Receives: Drug: Actinomycin D; Drug: Doxorubicin; Drug: Ifosfamide; Drug: Vincristine
CT1A: VHR Induction IRIVAExperimentalIrinotecan: 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.
Receives: Drug: Irinotecan; Drug: Actinomycin D; Drug: Ifosfamide; Drug: Vincristine
CT1B: HR Induction IVAActive 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.
Receives: Drug: Actinomycin D; Drug: Ifosfamide; Drug: Vincristine
CT1B: HR Induction IRIVAExperimentalIrinotecan: 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.
Receives: Drug: Irinotecan; Drug: Actinomycin D; Drug: Ifosfamide; Drug: Vincristine
RT1A: Preoperative RadiotherapyExperimentalTo be given either 41.4 Gy or 50.4 Gy prior to surgery
Receives: Radiation: radiotherapy
RT1A: Post operative radiotherapyActive comparatorTo be given either 41.4 Gy or 50.4 Gy following surgery
Receives: Radiation: radiotherapy
RT1B: Radiotherapy for resectable disease: dose escalatedExperimentalTo receive 50.4 Gy
Receives: Radiation: radiotherapy
RT1B: Radiotherapy for resectable disease: standard doseActive comparatorTo receive 41.4 Gy
Receives: Radiation: radiotherapy
RT1C: Radiotherapy for unresectable disease: dose escalatedExperimentalTo receive 59.4 Gy
Receives: Radiation: radiotherapy
RT1C: Radiotherapy for unresectable disease: standard doseActive comparatorTo receive 50.4 Gy
Receives: Radiation: radiotherapy
RT2: Radiotherapy to primary tumour and involved lymph nodesExperimentalRadiotherapy to the primary tumour and involved regional lymph nodes only
Receives: Radiation: radiotherapy
RT2: Radiotherapy to all metastatic sitesExperimentalRadiotherapy given to all metastatic sites
Receives: Radiation: radiotherapy
CT2A: VHR Maintenance - VCExperimentalVinorelbine: 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
Receives: Drug: Vinorelbine; Drug: Cyclophosphamide
CT2A: Maintenance -Stop treatmentNo interventionTo stop treatment at the point of randomisation
CT2B: HR Maintenance - VCExperimentalVinorelbine: 25 mg/m2 i.v. on days 1,8 and 15 Cyclophosphamide 25 mg/m2 orally daily for 28 days
Receives: Drug: Vinorelbine; Drug: Cyclophosphamide
CT2B: HR Maintenance - Stop TreatmentNo interventionTo stop treatment at the point of randomisation
CT3: Relpased Chemotherapy - VIRTActive 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
Receives: Drug: Irinotecan; Drug: Vincristine; Drug: Temozolomide
CT3: Relapsed Chemotherapy - VIRRExperimentalVincristine: 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.
Receives: Drug: Irinotecan; Drug: Vincristine; Drug: Regorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: From randomisation to first failure event, timeframe 36 months

  2. 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

    Measured: From randomisation to first failure event, timeframe 36 months

  3. 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

    Measured: From randomisation to first failure event, timeframe 36 months

  4. 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

    Measured: From randomisation to first failure event, timeframe 36 months

  5. 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

    Measured: Time from randomisation to first failure event, timeframe 36 months

  6. 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:

    • Regorafenib (R) added to vincristine and irinotecan (VIR) (VIRR)

    Measured: 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.

  7. 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

    Measured: Time from randomisation to first local failure event, timeframe 36 months

  8. 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

    Measured: Time from randomisation to first local failure event, timeframe 36 months

Secondary outcomes (28)

  1. Recommended Phase II Dose (Phase 1b)

    Based on tolerability, where tolerability is evaluated through the occurrence of dose limiting toxicity (DLT).

    Measured: From first patient first visit in dose finding study until appropriate dose level found, estimated 9 months

  2. Maximum Tolerated Dose (Phase 1b)

    Dose level at which no or one participant experiences a DLT when at least two of three to six participants experience a DLT at the next highest dose.

    Measured: From first patient first visit in dose finding study until appropriate dose level

  3. Toxicity (All chemotherapy randomisations)

    Categorised and graded using Common Terminology Criteria for Adverse Events

    Measured: From date of protocol defined treatment until 30 days after the administration of the last treatment

  4. Dose Limiting Toxicity (Phase 1b)

    Diarrhoea: Grade 3 for >3 days despite loperamide therapy Diarrhoea: Grade 4 despite loperamide therapy. Enterocolitis: Grade 3 or above Ileus: Grade 3 or above for more than 3 days Oral mucositis: Grade 3 above for >3 days despite optimal supportive care Persistent neutropenia or thrombocytopenia leading to delay of start of next course by >7 days; i.e. starting > day 28 Any grade 3 or 4 toxicity resulting in discontinuation of the new combination Any grade 5 toxicity

    Measured: From commencement of treatment until 21 days after the start of cycle 2 (each cycle is 21 days)

  5. Response (Phase 1b, CT1A, CT1B)

    defined as complete (CR) or partial response (PR) and is clinically defined. Patients who are not assessable for response - e.g. because of early stopping of treatment or death - will be assumed to be non-responders.

    Measured: Response assessed after course 3 (63 days) and 6 (126 days)

  6. Tolerability (CT3)

    To determine the tolerability of the regimens.

    Measured: From registration/randomisation until death/study endpoint

  7. Overall Survival (CT1A)

    Death from any cause

    Measured: From randomisation to death from any cause, assessed for 36 months

  8. Overall Survival (CT1B)

    Death from any cause

    Measured: From randomisation to death from any cause, assessed for 36 months

  9. Overall Survival (CT2A)

    Death from any cause

    Measured: From randomisation to death from any cause, assessed for 36 months

  10. Overall Survival (CT2B)

    Death from any cause

    Measured: From randomisation to death from any cause, assessed for 36 months

  11. Overall Survival (RT1A and RT1B)

    Death from any cause

    Measured: From randomisation to death from any cause, assessed for 36 months

  12. Overall Survival (RT1C)

    Death from any cause

    Measured: From RT1C randomisation to death from any cause, assessed for 36 months

  13. Overall Survival (RT2)

    Death from any cause

    Measured: From RT2 randomisation to death from any cause, as assessed for 36 months

  14. Overall Survival (CT3)

    To evaluate the anti-tumour activity and effect on overall survival of VIRR when compared to standard therapy

    Measured: 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.

  15. Overall Survival (all patients)

    Death from any cause

    Measured: From randomisation/registration to death from any cause, assessed for 36 months

  16. Acute wound complications and post-operative complications (RT1A and RT1B)

    specific grade 3 and above complications according to CTCAE v 4 and Clavien Dindo scale. Specific wound complications within the same time frame will also be collected

    Measured: Within 120 days from surgery

  17. Acute post-radiotherapy complications (All radiotherapy randomisations)

    any grade 3 and above event according to CTCAE v 4

    Measured: Within 120 days from start of radiotherapy

  18. Late complications (RT1A, RT1B. RT1C)

    specific grade 3 and above events according to CTCAE and Clavien-Dindo scale

    Measured: After 120 days from last local therapy

  19. Loco-regional failure-free survival (All radiotherapy randomisations)

    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 local, regional or distant failure. A regional event is relapse or progression of tumour at regional lymph nodes at any time even if there has been a prior distant failure.

    Measured: From randomisation to first local and/or regional failure event, assessed for 36 months

  20. Health related quality of life (RT1A and RT2) self-reported questionnaire completed by patient

    will be assessed using Pediatric quality of life questionnaire (PedsQL) for the paediatric population (under 18 years). The minimum score is 0 where quality of life is completely unaffected by the intervention to 4 where quality of life is severely affected.

    Measured: 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

  21. Health related quality of life (RT1A and RT2) self-reported questionnaire completed by the patient

    will be assessed using European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire 30 (EORTC QLQ-C30) for patients 18 years of age and over. The minimum score is 0 where quality of life is completely unaffected by the intervention to 4 where quality of life is severely affected.

    Measured: 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

  22. Health related quality of life (CT3) self-reported questionnaire completed by the patient

    will be assessed using Pediatric quality of life questionnaire (PedsQL) for the paediatric population (under 18 years). The minimum score is 0 where quality of life is completely unaffected by the intervention to 4 where quality of life is severely affected.

    Measured: 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

  23. Health related quality of life (CT3) self-reported questionnaire completed by the patient

    will be assessed using European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire 30 (EORTC QLQ-C30) for patients 18 years of age and over. The minimum score is 0 where quality of life is completely unaffected by the intervention to 4 where quality of life is severely affected.

    Measured: 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

  24. Acceptability and Palatability of Regorafenib (CT3)

    "Acceptability and Palatability Questionnaire" To evaluate the acceptability and palatability of regorafenib formulations

    Measured: 1 timepoint: Day 8 of cycle 1 (Each Cycle is 28 days)

  25. PET Response (if participating in PET Sub-study)

    assessed by PERCIST criteria and visual 'Deauville like' criteria

    Measured: After three cycles of chemotherapy (each cycle is 21 days)

  26. Event Free Survival (all patients)

    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

    Measured: From date of randomisation/registration to death from any cause, assessed for 36 months

  27. Event Free Survival (if participating in PET Sub-study)

    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

    Measured: From date of randomisation/registration to death from any cause, assessed for 36 months

  28. Local Failure Free Survival (if participating in PET Sub-study)

    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

    Measured: From date of randomisation/registration to first local failure event, assessed for 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2020
  2. Study start17 Sep 2020
  3. Primary completionJun 2030 (estimated)
  4. Study completionJun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,672 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04625907
Sponsor's protocol ID
RG_17-247
Other IDs
2018-000515-24, 45535982, 2018
Acronym
FaR-RMS
Status last verified
May 2024
First submitted
22 Nov 2019
Last updated
23 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Irinotecan, Actinomycin D and Doxorubicin in people with Rhabdomyosarcoma, run by University of Birmingham at 128 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 146 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 128 sites in United Kingdom, France, Australia, Spain, Switzerland and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Bridget Shaw (0121 414 2996, farrms@trials.bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event Free Survival (RT2) (time frame: From randomisation to first failure event, timeframe 36 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04625907.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2024.

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