FaR-RMS: An overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma
- Conditions
- RhabdomyosarcomaMedDRA version: 20.0Level: PTClassification code 10039022Term: RhabdomyosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000515-24-SE
- Lead Sponsor
- niversity of Birmingham
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 1672
Inclusion Criteria for study entry
1. Histologically confirmed diagnosis of RMS (except pleomorphic RMS)
2. Written informed consent from the patient and/or the parent/legal guardian
Inclusion criteria for all randomisations and registrations:
• 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
• Medically fit to receive treatment
Frontline chemotherapy specific inclusion:
• Entered in to the FaR-RMS study at diagnosis
• No prior treatment for RMS other than surgery
• Documented negative pregnancy test for female patients of childbearing potential
• 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
CT1a specific inclusion
• VHR disease
• Age = 6 months
• Available for randomisation =60 days after diagnostic biopsy/surgery
• Fractional Shortening = 28%
• Absolute neutrophil count =1.0x 10^9/L (except in patients with documented bone marrow disease)
• Platelets = 80 x 10^9/L (except in patients with documented bone marrow disease)
CT1b specific inclusion
• HR disease
• Age = 6 months
• Available for randomisation =60 days after diagnostic biopsy/surgery
• Absolute neutrophil count =1.0x 10^9/L
• Platelets = 80 x 10^9/L
Radiotherapy Inclusion
• Entered in to the FaR-RMS study (at diagnosis or prior to radiotherapy randomisation)
• VHR, HR and SR disease
• = 2 years of age
• Receiving frontline induction treatment as part of the FaR-RMS trial or with a IVA/IVADo based chemotherapy regimen. Note that, patients for whom ifosfamide has been replaced with cyclophosphamide will be eligible
• Documented negative pregnancy test for female patients of childbearing potential
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 delayed surgical resection of the primary tumor (local decision).
• Available for randomisation after cycle 3 and prior to the start of cycle 5 of induction chemotherapy for localised disease, or after cycle 6 and prior to the start of cycle 8 for metastatic disease
RT1b 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
• Higher Local Failure Risk (HLFR) based on presence of either of the following criteria:
• Unfavourable site
• Age = 18yrs
RT1c Specific Inclusion
• Primary radiotherapy indicated (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
• Higher Local Failure Risk (HLFR) based on presence of either of the following criteria:
• Unfavourable site
• Age = 18yrs
RT2 Specific Inclusion
• Available for randomisation after cycle 6 and before the start of cycle 9 of induction chemo
CT1a and CT1b specific 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
• Known hypersensitivity to any of the treatments or excipients
• Second malignancy
• Pregnant or breastfeeding women
• Urinary outflow obstruction that cannot be relieved prior to starting treatment
• Active inflammation of the urinary bladder (cystitis)
Radiotherapy specific exclusion
• Prior allo- or autologous Stem Cell Transplant
• Second malignancy
• Pregnant or breastfeeding women
• Receiving radiotherapy as brachytherapy
CT2a and CT2b specific Exclusion
• Prior allo- or autologous Stem Cell Transplant
• Uncontrolled inter current illness or active infection
• Second malignancy
• Pregnant or breastfeeding women
• Urinary outflow obstruction that cannot be relieved prior to starting treatment
• Active inflammation of the urinary bladder (cystitis)
CT3 specific 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
Exclusion criterias for Phase 1b are omittes as we do not intend to participate in this part of the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method