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

Product Name: Actinomycin D
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: dactinomycin
CAS Number: 50-76-0
Concentration unit: ?g microgram(s)
Concentration type: equal
Concentration number: 500-

Product Name: Doxorubicin
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: doxorubicin
CAS Number: 23214-92-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Product Name: Ifosfamide
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: ifosfamide
CAS Number: 3778-73-2
Concentration unit: g gram(s)
Concentration type: range
Concentration number: 1-2

Product Name: Irinotecan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Irinotecan
CAS Number: 97682-44-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 5-20

Product Name: Vincristine
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vincristine
CAS Number: 57-22-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Product Name: Vinorelbine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Vinorelbine
CAS Number: 71486-22-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Vinorelbine
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Vinorelbine
CAS Number: 71486-22-1
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 20-80

Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Cyclophosphamide
CAS Number: 50-18-0
Concentration unit: mg

Gender:
Female: yes
Male: yes

Inclusion criteria:
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
Phase 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/L

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 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/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
?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 potential
?RT1a 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 disease

RT1b and RT1c Specific Inclusion
?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

RT2 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 2-4

Maintenance specific Inclusion
?Received frontline induction chemotherapy as part of the FaR-RMS trial or with a IVA/IVADo based chemotherapy
?regimen
?Patients
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 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
?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