Eine Studie für Kinder und Erwachsene mit neu diagnostiziertem oder rezidiviertem Rhabdomyosarkom (RMS)

Product Name: Actinomycin DPharmaceutical Form: Lyophilisate for solution for injectionINN or Proposed INN: DACTINOMYCINCAS Number: 50-76-0Concentration unit: ?g microgram(s)Concentration type: equalConcentration number: 500-Product Name: DoxorubicinPharmaceutical Form: Solution for injection in vialINN or Proposed INN: DoxorubicinCAS Number: 23214-92-8Concentration unit: mg/ml milligram(s)/millilitreConcentration type: equalConcentration number: 2-Product Name: IfosfamidePharmaceutical Form: Powder for concentrate for solution for infusionINN or Proposed INN: IFOSFAMIDECAS Number: 3778-73-2Concentration unit: g gram(s)Concentration type: rangeConcentration number: 1-2Product Name: IrinotecanPharmaceutical Form: INN or Proposed INN: IRINOTECANCAS Number: 97682-44-5Concentration unit: mg/ml milligram(s)/millilitreConcentration type: equalConcentration number: 20-Product Name: VincristinePharmaceutical Form: Solution for injectionINN or Proposed INN: VINCRISTINECAS Number: 57-22-7Concentration unit: mg/ml milligram(s)/millilitreConcentration type: equalConcentration number: 1-Product Name: VinorelbinePharmaceutical Form: Concentrate for solution for infusionINN or Proposed INN: VINORELBINECAS Number: 71486-22-1Concentration unit: mg/ml milligram(s)/millilitreConcentration type: equalConcentration number: 10-Product Name: VinorelbinePharmaceutical Form: Capsule, softINN or Proposed INN: VINORELBINECAS Number: 71486-22-1Concentration unit: mg milligram(s)Concentration type: rangeConcentration number: 20-30Product Name: CyclophosphamidePharmaceutical Form: Powder for solution for injection/infusionINN or Proposed INN: CYCLOPHOSPHAMIDECAS Number: 50-18-0Concentration unit: mg milligram(s)Concentration type: rangeC

Gender: Female: yesMale: yes
Inclusion criteria: Inclusion Criteria for study entry1. Histologically confirmed diagnosis of RMS (except pleomorphic RMS)2. Written informed consent from the patient and/or the parent/legal guardianInclusion 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 treatmentFrontline 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 tohave Gilbert?s syndromePhase 1b Specific Inclusion? VHR disease? Age >12 months and =25 years? Adequate hepatic function: ALT or AST < 2.5 X ULN for age? Adequate renal function: estimated or measured creatinine clearance =60 ml/min/1.73 m2? Absolute neutrophil count =1.0x 10^9/L? Platelets = 80 x 10^9/LCT1a 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 109/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/LRadiotherapy 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 patients for whom. Note that patients for whom ifosfamide has been replaced with cyclophosphamide will be eligible? Documented negative pregnancy test for female patients of childbearing potentialRT1a and 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 diseaseRT1b and RT1c Specific Inclusion? Higher Local Failure Risk (HLFR) based on presence of either of the following criteria:o Unfavourable siteo Age = 18yrsRT1c 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, orafter cycle 6 and prior to the start of cycle 9 for metastatic diseaseRT2 Specific Inclusion? 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 2-4Maintenance specific Inclusion? Received frontline induction chemotherapy as part of the FaR-RMS trial or with a IVA/IVADo based chemotherapy regimen. Patients for whom ifosfamide has be
Exclusion criteria: Phase 1b specific 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? 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)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 brachytherapyCT2a 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? 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