Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04625907


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04625907
Ethics application status
Date submitted
22/11/2019
Date registered
12/11/2020
Date last updated
23/05/2024

Titles & IDs
Public title
FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma
Scientific title
FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma
Secondary ID [1] 0 0
2018-000515-24
Secondary ID [2] 0 0
RG_17-247
Universal Trial Number (UTN)
Trial acronym
FaR-RMS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rhabdomyosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Irinotecan
Treatment: Drugs - Actinomycin D
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Ifosfamide
Treatment: Drugs - Vincristine
Treatment: Drugs - Vinorelbine
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Temozolomide
Treatment: Other - radiotherapy
Treatment: Drugs - Regorafenib

Experimental: Phase 1b Dose finding: VHR induction - IRIVA - Irinotecan: an i.v. infusion over 1 hour on days 8,9,10,11 and 12 . For the phase 1b registration, starting dose of 20 mg/m2.

Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 as an As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on days 1 and 8 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.

Active comparator: CT1A: VHR induction - IVADO - Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on day 1 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1. Doxorubicin: 30 mg/m2 as an i.v infusion over 1 hour on days 1 and 2 on cycles 1-4

Experimental: CT1A: VHR Induction IRIVA - Irinotecan: an i.v. infusion over 1 hour on days 8,9,10,11 and 12 . Phase 2 recommended dose as determined by IRIVA dose finding arm Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on days 1 and 8 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.

Active comparator: CT1B: HR Induction IVA - Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on day 1 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.

Experimental: CT1B: HR Induction IRIVA - Irinotecan: an i.v. infusion over 1 hour on days 8,9,10,11 and 12 . Phase 2 recommended dose as determined by IRIVA dose finding arm Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on days 1 and 8 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.

Experimental: RT1A: Preoperative Radiotherapy - To be given either 41.4 Gy or 50.4 Gy prior to surgery

Active comparator: RT1A: Post operative radiotherapy - To be given either 41.4 Gy or 50.4 Gy following surgery

Experimental: RT1B: Radiotherapy for resectable disease: dose escalated - To receive 50.4 Gy

Active comparator: RT1B: Radiotherapy for resectable disease: standard dose - To receive 41.4 Gy

Experimental: RT1C: Radiotherapy for unresectable disease: dose escalated - To receive 59.4 Gy

Active comparator: RT1C: Radiotherapy for unresectable disease: standard dose - To receive 50.4 Gy

Experimental: RT2: Radiotherapy to primary tumour and involved lymph nodes - Radiotherapy to the primary tumour and involved regional lymph nodes only

Experimental: RT2: Radiotherapy to all metastatic sites - Radiotherapy given to all metastatic sites

Experimental: CT2A: VHR Maintenance - VC - Vinorelbine: 25 mg/m2 i.v. or 60 mg/m2 orally on days 1,8 and 15 Cyclophosphamide 25 mg/m2 orally daily for 28 days

No intervention: CT2A: Maintenance -Stop treatment - To stop treatment at the point of randomisation

Experimental: CT2B: HR Maintenance - VC - Vinorelbine: 25 mg/m2 i.v. on days 1,8 and 15 Cyclophosphamide 25 mg/m2 orally daily for 28 days

No intervention: CT2B: HR Maintenance - Stop Treatment - To stop treatment at the point of randomisation

Active comparator: CT3: Relpased Chemotherapy - VIRT - Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg) on days 1 and 8 Irinotecan: 50 mg/m2 as an i.v. infusion over 1 hour on days 1-5 Temozolomide: 125 mg/m2 (Escalate to 150mg/m2/day in Cycle 2 if no toxicity \> grade 3) as an oral tablets prior to vincristine and irinotecan on days 1-5

Experimental: CT3: Relapsed Chemotherapy - VIRR - Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg) on days 1 and 8 Irinotecan: 50 mg/m2 as an i.v. infusion over 1 hour on days 1-5 Regorafenib: Children between 6 and 24 months = 65 mg/m2, children less than 12 and/or less than 40kg dose = 82 mg/m2 Maximum 120 mg, Fixed dose of 120 mg for patients over 12 years of age AND = 40 kg, as an oral tablets on days 8 to 21.


Treatment: Drugs: Irinotecan
antineoplastic enzyme inhibitor

Treatment: Drugs: Actinomycin D
Antineoplastic agent that is a polypeptide antibiotic

Treatment: Drugs: Doxorubicin
An anthracycline topoisomerase inhibitor isolated from streptpmyces peucetius var. casesius

Treatment: Drugs: Ifosfamide
chemotherapeutic agent chemically related to the nitrogen mustards and is a synthetic analog of cyclophosphamide

Treatment: Drugs: Vincristine
anti neoplastic vinca alkaloid agent

Treatment: Drugs: Vinorelbine
vinca alkaloid with a role as an antineoplastic agent

Treatment: Drugs: Cyclophosphamide
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent

Treatment: Drugs: Temozolomide
oral antineoplastic alkylating agent

Treatment: Other: radiotherapy
Ionising radiation

Treatment: Drugs: Regorafenib
Oral multi-kinase inhibitor that targets a broad range of angiogenic, stromal and oncogenic kinases, including vascular endothelial growth factor receptors (VEFGR) 1, 2 and 3, tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (TIE2), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR), c-KIT, RET, RAF-1 and BRAF (wild-type and V600E mutant).
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival (RT2)
Timepoint [1] 0 0
From randomisation to first failure event, timeframe 36 months
Primary outcome [2] 0 0
Event Free Survival (CT1A)
Timepoint [2] 0 0
From randomisation to first failure event, timeframe 36 months
Primary outcome [3] 0 0
Event Free Survival (CT1B)
Timepoint [3] 0 0
From randomisation to first failure event, timeframe 36 months
Primary outcome [4] 0 0
Event Free Survival (CT2A)
Timepoint [4] 0 0
From randomisation to first failure event, timeframe 36 months
Primary outcome [5] 0 0
Event Free Survival (CT2B)
Timepoint [5] 0 0
Time from randomisation to first failure event, timeframe 36 months
Primary outcome [6] 0 0
Event Free Survival (CT3)
Timepoint [6] 0 0
Patients will be followed up for a minimum of 6 years from trial entry (or 5 years from end of relapsed trial treatment, whichever comes later). Patients will be followed up for progression and death until the end of trial definition has been met.
Primary outcome [7] 0 0
Local Failure Free Survival (RT1A and RT1B)
Timepoint [7] 0 0
Time from randomisation to first local failure event, timeframe 36 months
Primary outcome [8] 0 0
Local Failure Free Survival (RT1C)
Timepoint [8] 0 0
Time from randomisation to first local failure event, timeframe 36 months
Secondary outcome [1] 0 0
Recommended Phase II Dose (Phase 1b)
Timepoint [1] 0 0
From first patient first visit in dose finding study until appropriate dose level found, estimated 9 months
Secondary outcome [2] 0 0
Maximum Tolerated Dose (Phase 1b)
Timepoint [2] 0 0
From first patient first visit in dose finding study until appropriate dose level
Secondary outcome [3] 0 0
Toxicity (All chemotherapy randomisations)
Timepoint [3] 0 0
From date of protocol defined treatment until 30 days after the administration of the last treatment
Secondary outcome [4] 0 0
Dose Limiting Toxicity (Phase 1b)
Timepoint [4] 0 0
From commencement of treatment until 21 days after the start of cycle 2 (each cycle is 21 days)
Secondary outcome [5] 0 0
Response (Phase 1b, CT1A, CT1B)
Timepoint [5] 0 0
Response assessed after course 3 (63 days) and 6 (126 days)
Secondary outcome [6] 0 0
Tolerability (CT3)
Timepoint [6] 0 0
From registration/randomisation until death/study endpoint
Secondary outcome [7] 0 0
Overall Survival (CT1A)
Timepoint [7] 0 0
From randomisation to death from any cause, assessed for 36 months
Secondary outcome [8] 0 0
Overall Survival (CT1B)
Timepoint [8] 0 0
From randomisation to death from any cause, assessed for 36 months
Secondary outcome [9] 0 0
Overall Survival (CT2A)
Timepoint [9] 0 0
From randomisation to death from any cause, assessed for 36 months
Secondary outcome [10] 0 0
Overall Survival (CT2B)
Timepoint [10] 0 0
From randomisation to death from any cause, assessed for 36 months
Secondary outcome [11] 0 0
Overall Survival (RT1A and RT1B)
Timepoint [11] 0 0
From randomisation to death from any cause, assessed for 36 months
Secondary outcome [12] 0 0
Overall Survival (RT1C)
Timepoint [12] 0 0
From RT1C randomisation to death from any cause, assessed for 36 months
Secondary outcome [13] 0 0
Overall Survival (RT2)
Timepoint [13] 0 0
From RT2 randomisation to death from any cause, as assessed for 36 months
Secondary outcome [14] 0 0
Overall Survival (CT3)
Timepoint [14] 0 0
Patients will be followed up for a minimum of 6 years from trial entry (or 5 years from end of relapsed trial treatment, whichever comes later). Patients will be followed up for progression and death until the end of trial definition has been met.
Secondary outcome [15] 0 0
Overall Survival (all patients)
Timepoint [15] 0 0
From randomisation/registration to death from any cause, assessed for 36 months
Secondary outcome [16] 0 0
Acute wound complications and post-operative complications (RT1A and RT1B)
Timepoint [16] 0 0
Within 120 days from surgery
Secondary outcome [17] 0 0
Acute post-radiotherapy complications (All radiotherapy randomisations)
Timepoint [17] 0 0
Within 120 days from start of radiotherapy
Secondary outcome [18] 0 0
Late complications (RT1A, RT1B. RT1C)
Timepoint [18] 0 0
After 120 days from last local therapy
Secondary outcome [19] 0 0
Loco-regional failure-free survival (All radiotherapy randomisations)
Timepoint [19] 0 0
From randomisation to first local and/or regional failure event, assessed for 36 months
Secondary outcome [20] 0 0
Health related quality of life (RT1A and RT2) self-reported questionnaire completed by patient
Timepoint [20] 0 0
4 timepoints: 1) 1 day of start of radiotherapy, 2) at completion of radiotherapy, average 5 weeks after start of radiotherapy, 3) 3 months and 4) 24 months following radiotherapy
Secondary outcome [21] 0 0
Health related quality of life (RT1A and RT2) self-reported questionnaire completed by the patient
Timepoint [21] 0 0
4 timepoints: 1) 1 day of start of radiotherapy, 2) at completion of radiotherapy, average 5 weeks after start of radiotherapy, 3) 3 months and 4) 24 months following radiotherapy
Secondary outcome [22] 0 0
Health related quality of life (CT3) self-reported questionnaire completed by the patient
Timepoint [22] 0 0
3 timepoints: Each Cycle is 28 days. Timepoint 1: Day 0 of cycle 1 (prior to starting treatment), Timepoint 2 day 0 cycle 3, Timepoint 3) day 0 cycle 5
Secondary outcome [23] 0 0
Health related quality of life (CT3) self-reported questionnaire completed by the patient
Timepoint [23] 0 0
3 timepoints: Each Cycle is 28 days. Timepoint 1: Day 0 of cycle 1 (prior to starting treatment), Timepoint 2 day 0 cycle 3, Timepoint 3) day 0 cycle 5
Secondary outcome [24] 0 0
Acceptability and Palatability of Regorafenib (CT3)
Timepoint [24] 0 0
1 timepoint: Day 8 of cycle 1 (Each Cycle is 28 days)
Secondary outcome [25] 0 0
PET Response (if participating in PET Sub-study)
Timepoint [25] 0 0
After three cycles of chemotherapy (each cycle is 21 days)
Secondary outcome [26] 0 0
Event Free Survival (all patients)
Timepoint [26] 0 0
From date of randomisation/registration to death from any cause, assessed for 36 months
Secondary outcome [27] 0 0
Event Free Survival (if participating in PET Sub-study)
Timepoint [27] 0 0
From date of randomisation/registration to death from any cause, assessed for 36 months
Secondary outcome [28] 0 0
Local Failure Free Survival (if participating in PET Sub-study)
Timepoint [28] 0 0
From date of randomisation/registration to first local failure event, assessed for 36 months

Eligibility
Key inclusion criteria
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
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2030
Actual
Sample size
Target
1672
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Queensland Children's Hospital - Brisbane
Recruitment hospital [2] 0 0
Chris O'brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
Monash Children's Hospital - Clayton
Recruitment hospital [4] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Royal Childrens Hospital Melbourne - Melbourne
Recruitment hospital [6] 0 0
John Hunter Children's Hospital - New Lambton Heights
Recruitment hospital [7] 0 0
Perth Children's Hospital - Perth
Recruitment hospital [8] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [9] 0 0
The Childrens Hospital At Westmead - Sydney
Recruitment hospital [10] 0 0
Westmead Hospital - Westmead
Recruitment hospital [11] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
- Camperdown
Recruitment postcode(s) [3] 0 0
- Clayton
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
2310 - New Lambton Heights
Recruitment postcode(s) [6] 0 0
- Perth
Recruitment postcode(s) [7] 0 0
- Sydney
Recruitment postcode(s) [8] 0 0
- Westmead
Recruitment postcode(s) [9] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Linz
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Belgium
State/province [3] 0 0
Brussels
Country [4] 0 0
Belgium
State/province [4] 0 0
Bruxelles
Country [5] 0 0
Belgium
State/province [5] 0 0
Gent
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Belgium
State/province [7] 0 0
Liège
Country [8] 0 0
Czechia
State/province [8] 0 0
Brno
Country [9] 0 0
Denmark
State/province [9] 0 0
Aarhus
Country [10] 0 0
Denmark
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Copenhagen
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La Réunion
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Lille
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Lyon
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Wirral

Funding & Sponsors
Primary sponsor type
Other
Name
University of Birmingham
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Meriel Jenney
Address 0 0
Chief Investigator
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Bridget Shaw
Address 0 0
Country 0 0
Phone 0 0
0121 414 2996
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04625907

Additional trial details provided through ANZCTR
Accrual to date
5
Recruiting in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 47
The Children's Hospital at Westmead
Recruitment hospital [2] 48
John Hunter Children's Hospital
Recruitment hospital [3] 49
Monash Children’s Hospital
Recruitment hospital [4] 50
Perth Children's Hospital
Recruitment hospital [5] 51
The Royal Childrens Hospital
Recruitment hospital [6] 52
Sydney Children's Hospital
Recruitment hospital [7] 53
Womens and Childrens Hospital
Recruitment hospital [8] 54
Peter MacCallum Cancer Centre
Recruitment hospital [9] 55
Chris O’Brien Lifehouse
Recruitment hospital [10] 56
Princess Alexandra Hospital
Recruitment hospital [11] 57
Westmead Hospital
Recruitment hospital [12] 58
Queensland Children's Hospital
Recruitment postcode(s) [1] 52
2145
Recruitment postcode(s) [2] 53
2305
Recruitment postcode(s) [3] 54
3168
Recruitment postcode(s) [4] 55
6009
Recruitment postcode(s) [5] 56
3052
Recruitment postcode(s) [6] 57
2031
Recruitment postcode(s) [7] 58
5006
Recruitment postcode(s) [8] 59
3000
Recruitment postcode(s) [9] 60
2050
Recruitment postcode(s) [10] 61
4102
Recruitment postcode(s) [11] 62
4101
Recruiting in New Zealand
Province(s)/district(s)
New Zealand sites to open: Christchurch Hospital Starship Children's Hospital
Funding & Sponsors
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australian and New Zealand Children's Haematology and Oncology Group
Primary sponsor address
27-31 Wright Street, Clayton VIC 3168
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
 
Public notes

Contacts
Principal investigator
Title 201 0
Dr
Name 201 0
Marty Campbell
Address 201 0
Country 201 0
Australia
Phone 201 0
Fax 201 0
Email 201 0
[email protected]
Contact person for public queries
Title 202 0
Mrs
Name 202 0
Robyn Strong
Address 202 0
27-31 Wright Street, Clayton, VIC, 3168
Country 202 0
Australia
Phone 202 0
+613 8572 2684
Fax 202 0
+613 9902 4810
Email 202 0
[email protected]
Contact person for scientific queries
Title 203 0
Dr
Name 203 0
Marty Campbell
Address 203 0
Country 203 0
Australia
Phone 203 0
Fax 203 0
Email 203 0
[email protected]