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)
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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