Informations générales (source: ClinicalTrials.gov)
FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS)
Interventional
Phase 1/Phase 2
University of Birmingham (Voir sur ClinicalTrials)
septembre 2020
juin 2030
29 juin 2024
FaR-RMS is an over-arching study for children and adults with newly diagnosed and
relapsed rhabdomyosarcoma (RMS)
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:40 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | V�ronique MINARD-COLIN | 24/05/2024 10:47:26 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Armand Trousseau-La Roche Guyon | H Boutroux | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Eugne Marquis De Rennes - Rennes - France | J Leseur | Contact (sur clinicalTrials) | |||
| Centre Francois Baclesse - Caen - France | F Missohou | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Regional Universitaire Besancon - Hopital Jean Minjoz - Besançon - France | S Klein | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Regional Universitaire Brest - Hopital Morvan - Brest - France | L Carausu | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Regional Universitaire De Tours - Hopital Clocheville - Tours - France | J Serre | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire D'angers - Angers - France | S Proust | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Bordeaux - Hopital Pellegrin - Bordeaux - France | C Verite | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Caen - Caen - France | D Bodet | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Grenoble - Grenoble - France | D Plantaz | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Nancy - Nancy - France | L Mansuy | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Nantes - Nantes - France | M Cleirec | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Poitiers - Poitiers - France | F Millot | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Rennes - Hopital Pontchaillou - Rennes - France | S Taque | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Rouen - Rouen - France | A Marie Cardine | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire De Toulouse - Hopital Des Enfants - Toulouse - France | MP Castex | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire Dijon Bourgogne - Hopital D'enfants - Dijon - France | C Briandet | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire Haut Levque - Pessac - France | A Huchet | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire La Reunion - La Réunion - France | Y Reguerre | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire Saint-etienne - Saint-Étienne - France | C Berger | Contact (sur clinicalTrials) | |||
| Centre Leon Berard - Lyon - France | N Corradini | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - Lille - France | A Defachelles | Contact (sur clinicalTrials) | |||
| Chu De Reims - Reims - France | C Pluchart | Contact (sur clinicalTrials) | |||
| Hopital De La Timone (ap-hm) - Marseille - France | A Rome | Contact (sur clinicalTrials) | |||
| Strasbourg Hautepierre - Strasbourg - France | S Jannier | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria for study entry - Mandatory at first point of study entry
1. Histologically confirmed diagnosis of RMS (except pleomorphic RMS)
2. Written informed consent from the patient and/or the parent/legal guardian
Phase 1b Dose Finding - IRIVA Inclusion
1. Entered in to the FaR-RMS study at diagnosis
2. Very High Risk disease
3. Age >12 months and ≤25 years
4. No prior treatment for RMS other than surgery
5. Medically fit to receive treatment
6. Adequate hepatic function:
1. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age, unless the
patient is known to have Gilbert's syndrome
2. ALT or AST < 2.5 X ULN for age
7. Absolute neutrophil count ≥1.0x 109/L
8. Platelets ≥ 80 x 109/L
9. Adequate renal function: estimated or measured creatinine clearance ≥60 ml/min/1.73
m2
10. Documented negative pregnancy test for female patients of childbearing potential
11. 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
12. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Weight <10kg
2. Active > grade 2 diarrhoea
3. Prior allo- or autologous Stem Cell Transplant
4. Uncontrolled inter-current illness or active infection
5. Pre-existing medical condition precluding treatment
6. Urinary outflow obstruction that cannot be relieved prior to starting treatment
7. Active inflammation of the urinary bladder (cystitis)
8. Known hypersensitivity to any of the treatments or excipients
9. Second malignancy
10. Pregnant or breastfeeding women
Frontline chemotherapy randomisation Very High Risk - CT1a Inclusion
1. Entered in to the FaR-RMS study at diagnosis
2. Very High Risk disease
3. Age ≥ 6 months
4. Available for randomisation ≤60 days after diagnostic biopsy/surgery
5. No prior treatment for RMS other than surgery
6. Medically fit to receive treatment
7. 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
8. Absolute neutrophil count ≥1.0x 109/L (except in patients with documented bone
marrow disease)
9. Platelets ≥ 80 x 109/L (except in patients with documented bone marrow disease)
10. Fractional Shortening ≥ 28%
11. Documented negative pregnancy test for female patients of childbearing potential
12. 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
13. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Active > grade 2 diarrhoea
2. Prior allo- or autologous Stem Cell Transplant
3. Uncontrolled inter-current illness or active infection
4. Pre-existing medical condition precluding treatment
5. Urinary outflow obstruction that cannot be relieved prior to starting treatment
6. Active inflammation of the urinary bladder (cystitis)
7. Known hypersensitivity to any of the treatments or excipients
8. Second malignancy
9. Pregnant or breastfeeding women
Frontline chemotherapy randomisation High Risk - CT1b Inclusion
1. Entered in to the FaR-RMS study at diagnosis
2. High Risk disease
3. Age ≥ 6 months
4. Available for randomisation ≤60 days after diagnostic biopsy/surgery
5. No prior treatment for RMS other than surgery
6. Medically fit to receive treatment
7. 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
8. Absolute neutrophil count ≥1.0x 109/L
9. Platelets ≥ 80 x 109/L
10. Documented negative pregnancy test for female patients of childbearing potential
11. 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
12. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Active > grade 2 diarrhoea
2. Prior allo- or autologous Stem Cell Transplant
3. Uncontrolled inter-current illness or active infection
4. Pre-existing medical condition precluding treatment
5. Urinary outflow obstruction that cannot be relieved prior to starting treatment
6. Active inflammation of the urinary bladder (cystitis)
7. Known hypersensitivity to any of the treatments or excipients
8. Second malignancy
9. Pregnant or breastfeeding women
Frontline Radiotherapy Note: eligible patients may enter multiple radiotherapy
randomisations.
Radiotherapy Inclusion - for all radiotherapy randomisations
1. Entered in to the FaR-RMS study (at diagnosis or prior to radiotherapy
randomisation)
2. Very High Risk, High Risk and Standard Risk disease
3. ≥ 2 years of age
4. 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
5. Patient assessed as medically fit to receive the radiotherapy
6. Documented negative pregnancy test for female patients of childbearing potential
7. 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
8. Written informed consent from the patient and/or the parent/legal guardian
Radiotherapy Exclusion - for all radiotherapy randomisations
1. Prior allo- or autologous Stem Cell Transplant
2. Second malignancy
3. Pregnant or breastfeeding women
4. Receiving radiotherapy as brachytherapy
RT1a Specific Inclusion
1. Primary tumour deemed resectable (predicted R0/ R1 resection feasible) after 3
cycles of induction chemotherapy (6 cycles for metastatic disease)
2. Adjuvant radiotherapy required in addition to surgical resection (local decision).
3. 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
1. Primary tumour deemed resectable (predicted R0/R1 resection) after 3 cycles of
induction chemotherapy (6 cycles for metastatic disease).
2. Adjuvant radiotherapy required in addition to surgical resection (local decision)
3. Higher Local Failure Risk (HLFR) based on presence of either of the following
criteria:
1. Unfavourable site
2. Age ≥ 18yrs
4. 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
1. Primary radiotherapy indicated (local decision)
2. Higher Local Failure Risk (HLFR) based on either of the following criteria:
1. Unfavourable site
2. Age ≥ 18yrs
3. 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
1. Available for randomisation after cycle 6 and before the start of cycle 9 of
induction chemotherapy.
2. 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.
1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. Very High Risk disease
3. 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
4. Completed 11 cycles of VnC maintenance treatment (either oral or IV regimens)
5. No evidence of progressive disease
6. Absence of severe vincristine neuropathy - i.e requiring discontinuation of
vincristine treatment)
7. Medically fit to continue to receive treatment
8. 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
9. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Prior allo- or autologous Stem Cell Transplant
2. Uncontrolled intercurrent illness or active infection
3. Urinary outflow obstruction that cannot be relieved prior to starting treatment
4. Active inflammation of the urinary bladder (cystitis)
5. Second malignancy
6. Pregnant or breastfeeding women
Maintenance chemotherapy (High Risk) - CT2b Randomisation must take place during the 6th
cycle of maintenance chemotherapy. Inclusion
1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. High Risk disease
3. 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
4. Completed 5 cycles of VnC maintenance treatment
5. No evidence of progressive disease
6. Absence of severe vincristine neuropathy i.e. requiring discontinuation of
vincristine treatment
7. Medically fit to continue to receive treatment
8. 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
9. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Prior allo- or autologous Stem Cell Transplant
2. Uncontrolled inter current illness or active infection
3. Urinary outflow obstruction that cannot be relieved prior to starting treatment
4. Active inflammation of the urinary bladder (cystitis)
5. Second malignancy
6. Pregnant or breastfeeding women
CT3 Relapsed Chemotherapy
Inclusion:
1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. First or subsequent relapse of histologically verified RMS
3. Age ≥ 6 months
4. Measurable or evaluable disease
5. No cytotoxic chemotherapy or other investigational medicinal product (IMP) within
previous three weeks: within two weeks for vinorelbine and cyclophosphamide
maintenance chemotherapy
6. Medically fit to receive trial treatment
7. Documented negative pregnancy test for female patients of childbearing potential
within 7 days of planned randomisation
8. 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
9. Written informed consent from the patient and/or the parent/legal guardian
Exclusion:
1. Progression during frontline therapy without previous response (=Refractory to first
line treatment)
2. Prior regorafenib or temozolomide
3. Active > grade 1 diarrhoea
4. ALT or AST >3.0 x upper limit normal (ULN)
5. Bilirubin, Total >1.5 x ULN; total bilirubin is allowed up to 3 x ULN if Gilbert's
syndrome is documented
6. 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)
7. Uncontrolled hypertension > 95th centile for age and gender
8. Prior allo- or autologous Stem Cell Transplant
9. Uncontrolled inter-current illness or active infection
10. Pre-existing medical condition precluding treatment
11. Known hypersensitivity to any of the treatments or excipients
12. Second malignancy
13. Pregnant or breastfeeding women
1. Histologically confirmed diagnosis of RMS (except pleomorphic RMS)
2. Written informed consent from the patient and/or the parent/legal guardian
Phase 1b Dose Finding - IRIVA Inclusion
1. Entered in to the FaR-RMS study at diagnosis
2. Very High Risk disease
3. Age >12 months and ≤25 years
4. No prior treatment for RMS other than surgery
5. Medically fit to receive treatment
6. Adequate hepatic function:
1. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age, unless the
patient is known to have Gilbert's syndrome
2. ALT or AST < 2.5 X ULN for age
7. Absolute neutrophil count ≥1.0x 109/L
8. Platelets ≥ 80 x 109/L
9. Adequate renal function: estimated or measured creatinine clearance ≥60 ml/min/1.73
m2
10. Documented negative pregnancy test for female patients of childbearing potential
11. 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
12. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Weight <10kg
2. Active > grade 2 diarrhoea
3. Prior allo- or autologous Stem Cell Transplant
4. Uncontrolled inter-current illness or active infection
5. Pre-existing medical condition precluding treatment
6. Urinary outflow obstruction that cannot be relieved prior to starting treatment
7. Active inflammation of the urinary bladder (cystitis)
8. Known hypersensitivity to any of the treatments or excipients
9. Second malignancy
10. Pregnant or breastfeeding women
Frontline chemotherapy randomisation Very High Risk - CT1a Inclusion
1. Entered in to the FaR-RMS study at diagnosis
2. Very High Risk disease
3. Age ≥ 6 months
4. Available for randomisation ≤60 days after diagnostic biopsy/surgery
5. No prior treatment for RMS other than surgery
6. Medically fit to receive treatment
7. 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
8. Absolute neutrophil count ≥1.0x 109/L (except in patients with documented bone
marrow disease)
9. Platelets ≥ 80 x 109/L (except in patients with documented bone marrow disease)
10. Fractional Shortening ≥ 28%
11. Documented negative pregnancy test for female patients of childbearing potential
12. 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
13. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Active > grade 2 diarrhoea
2. Prior allo- or autologous Stem Cell Transplant
3. Uncontrolled inter-current illness or active infection
4. Pre-existing medical condition precluding treatment
5. Urinary outflow obstruction that cannot be relieved prior to starting treatment
6. Active inflammation of the urinary bladder (cystitis)
7. Known hypersensitivity to any of the treatments or excipients
8. Second malignancy
9. Pregnant or breastfeeding women
Frontline chemotherapy randomisation High Risk - CT1b Inclusion
1. Entered in to the FaR-RMS study at diagnosis
2. High Risk disease
3. Age ≥ 6 months
4. Available for randomisation ≤60 days after diagnostic biopsy/surgery
5. No prior treatment for RMS other than surgery
6. Medically fit to receive treatment
7. 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
8. Absolute neutrophil count ≥1.0x 109/L
9. Platelets ≥ 80 x 109/L
10. Documented negative pregnancy test for female patients of childbearing potential
11. 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
12. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Active > grade 2 diarrhoea
2. Prior allo- or autologous Stem Cell Transplant
3. Uncontrolled inter-current illness or active infection
4. Pre-existing medical condition precluding treatment
5. Urinary outflow obstruction that cannot be relieved prior to starting treatment
6. Active inflammation of the urinary bladder (cystitis)
7. Known hypersensitivity to any of the treatments or excipients
8. Second malignancy
9. Pregnant or breastfeeding women
Frontline Radiotherapy Note: eligible patients may enter multiple radiotherapy
randomisations.
Radiotherapy Inclusion - for all radiotherapy randomisations
1. Entered in to the FaR-RMS study (at diagnosis or prior to radiotherapy
randomisation)
2. Very High Risk, High Risk and Standard Risk disease
3. ≥ 2 years of age
4. 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
5. Patient assessed as medically fit to receive the radiotherapy
6. Documented negative pregnancy test for female patients of childbearing potential
7. 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
8. Written informed consent from the patient and/or the parent/legal guardian
Radiotherapy Exclusion - for all radiotherapy randomisations
1. Prior allo- or autologous Stem Cell Transplant
2. Second malignancy
3. Pregnant or breastfeeding women
4. Receiving radiotherapy as brachytherapy
RT1a Specific Inclusion
1. Primary tumour deemed resectable (predicted R0/ R1 resection feasible) after 3
cycles of induction chemotherapy (6 cycles for metastatic disease)
2. Adjuvant radiotherapy required in addition to surgical resection (local decision).
3. 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
1. Primary tumour deemed resectable (predicted R0/R1 resection) after 3 cycles of
induction chemotherapy (6 cycles for metastatic disease).
2. Adjuvant radiotherapy required in addition to surgical resection (local decision)
3. Higher Local Failure Risk (HLFR) based on presence of either of the following
criteria:
1. Unfavourable site
2. Age ≥ 18yrs
4. 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
1. Primary radiotherapy indicated (local decision)
2. Higher Local Failure Risk (HLFR) based on either of the following criteria:
1. Unfavourable site
2. Age ≥ 18yrs
3. 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
1. Available for randomisation after cycle 6 and before the start of cycle 9 of
induction chemotherapy.
2. 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.
1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. Very High Risk disease
3. 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
4. Completed 11 cycles of VnC maintenance treatment (either oral or IV regimens)
5. No evidence of progressive disease
6. Absence of severe vincristine neuropathy - i.e requiring discontinuation of
vincristine treatment)
7. Medically fit to continue to receive treatment
8. 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
9. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Prior allo- or autologous Stem Cell Transplant
2. Uncontrolled intercurrent illness or active infection
3. Urinary outflow obstruction that cannot be relieved prior to starting treatment
4. Active inflammation of the urinary bladder (cystitis)
5. Second malignancy
6. Pregnant or breastfeeding women
Maintenance chemotherapy (High Risk) - CT2b Randomisation must take place during the 6th
cycle of maintenance chemotherapy. Inclusion
1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. High Risk disease
3. 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
4. Completed 5 cycles of VnC maintenance treatment
5. No evidence of progressive disease
6. Absence of severe vincristine neuropathy i.e. requiring discontinuation of
vincristine treatment
7. Medically fit to continue to receive treatment
8. 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
9. Written informed consent from the patient and/or the parent/legal guardian
Exclusion
1. Prior allo- or autologous Stem Cell Transplant
2. Uncontrolled inter current illness or active infection
3. Urinary outflow obstruction that cannot be relieved prior to starting treatment
4. Active inflammation of the urinary bladder (cystitis)
5. Second malignancy
6. Pregnant or breastfeeding women
CT3 Relapsed Chemotherapy
Inclusion:
1. Entered in to the FaR-RMS study (at diagnosis or at any subsequent time point)
2. First or subsequent relapse of histologically verified RMS
3. Age ≥ 6 months
4. Measurable or evaluable disease
5. No cytotoxic chemotherapy or other investigational medicinal product (IMP) within
previous three weeks: within two weeks for vinorelbine and cyclophosphamide
maintenance chemotherapy
6. Medically fit to receive trial treatment
7. Documented negative pregnancy test for female patients of childbearing potential
within 7 days of planned randomisation
8. 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
9. Written informed consent from the patient and/or the parent/legal guardian
Exclusion:
1. Progression during frontline therapy without previous response (=Refractory to first
line treatment)
2. Prior regorafenib or temozolomide
3. Active > grade 1 diarrhoea
4. ALT or AST >3.0 x upper limit normal (ULN)
5. Bilirubin, Total >1.5 x ULN; total bilirubin is allowed up to 3 x ULN if Gilbert's
syndrome is documented
6. 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)
7. Uncontrolled hypertension > 95th centile for age and gender
8. Prior allo- or autologous Stem Cell Transplant
9. Uncontrolled inter-current illness or active infection
10. Pre-existing medical condition precluding treatment
11. Known hypersensitivity to any of the treatments or excipients
12. Second malignancy
13. Pregnant or breastfeeding women