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

A vizsgálat adatai

Ki végzi

University of Birmingham

Azonosító

NCT04625907EU 2024-510579-40-00

A regiszteradat frissítve

2024. május 23.

Eredeti leírás

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

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

Bevonási feltételek: 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 :; 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 :; 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; 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:; 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.

ClinicalTrials.gov NCT04625907 · EU CTIS 2024-510579-40-00