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Status:

RECRUITING

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

Lead Sponsor:

University of Birmingham

Conditions:

Rhabdomyosarcoma

Eligibility:

All Genders

Phase:

PHASE1

PHASE2

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. F...

Eligibility Criteria

Inclusion

  • for study entry - Mandatory at first point of study entry
  • Histologically confirmed diagnosis of RMS (except pleomorphic RMS)
  • Written informed consent from the patient and/or the parent/legal guardian
  • Phase 1b Dose Finding - IRIVA Inclusion
  • 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
  • Written informed consent from the patient and/or the parent/legal guardian
  • Exclusion
  • 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
  • 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 :
  • a. 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
  • Exclusion
  • 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 :
  • a. 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
  • Exclusion
  • 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
  • a. 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
  • Exclusion
  • 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
  • Exclusion
  • 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
  • Inclusion:
  • 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
  • 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

Exclusion

  • Exclusion:
  • 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

Key Trial Info

Start Date :

September 17 2020

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

June 1 2030

Estimated Enrollment :

1672 Patients enrolled

Trial Details

Trial ID

NCT04625907

Start Date

September 17 2020

End Date

June 1 2030

Last Update

May 23 2024

Active Locations (128)

Enter a location and click search to find clinical trials sorted by distance.

Page 1 of 32 (128 locations)

1

Queensland Children's Hospital

Brisbane, Australia, 4101

2

Chris O'brien Lifehouse

Camperdown, Australia

3

Monash Children's Hospital

Clayton, Australia

4

Peter Maccallum Cancer Centre

Melbourne, Australia