An overarching study for children and adults with frontline and relapsed rhabdomyosarcoma

Not Applicable

• Conditions: Rhabdomyosarcoma; Cancer

• Registration Number: ISRCTN45535982
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-06-11
• Last Update Posted: 8 July 2024
• Study Completion: 2030-03-01

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 1672

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:
1. 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
2. Written informed consent from the patient and/or the parent/legal guardian
3. Medically fit to receive treatment

Frontline chemotherapy specific inclusion:
1. Entered into the FaR-RMS study at diagnosis
2. No prior treatment for RMS other than surgery
3. Documented negative pregnancy test for female patients of childbearing potential
4. 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:
1. VHR disease
2. Age >12 months and =25 years
3. Adequate hepatic function: ALT or AST < 2.5 X ULN for age
4. Adequate renal function: estimated or measured creatinine clearance =60 ml/min/1.73 m2
5. Absolute neutrophil count =1.0x 10^9/L
6. Platelets = 80 x 10^9/L

CT1a specific inclusion:
1. VHR disease
2. Age = 6 months
3. Available for randomisation =60 days after diagnostic biopsy/surgery
4. Fractional Shortening = 28%
5. Absolute neutrophil count =1.0x 10^9/L (except in patients with documented bone marrow disease)
6. Platelets = 80 x 109/L (except in patients with documented bone marrow disease)

CT1b specific inclusion:
1. HR disease
2. Age = 6 months
3. Available for randomisation =60 days after diagnostic biopsy/surgery
4. Absolute neutrophil count =1.0x 10^9/L
5. Platelets = 80 x 10^9/L

Radiotherapy inclusion:
1. Entered into the FaR-RMS study (at diagnosis or prior to radiotherapy randomisation)
2. VHR, HR and SR 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. Note that patients for whom ifosfamide has been replaced with cyclophosphamide will be eligible
5. Documented negative pregnancy test for female patients of childbearing potential

RT1a and RT1b 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 and RT1c specific inclusion:
1. Higher Local Failure Risk (HLFR) based on presence of either of the following criteria:
2. Unfavourable site
3. Age = 18yrs

RT1c specific inclusion:
1. Primary radiotherapy indicated (local decision)
2. 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:
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

Maintenance specific Inclusion:
1. Received frontline induction chemotherapy as part of the FaR-RMS trial or with a IVA/IVADo based chemotherapy regi

Exclusion Criteria

Phase 1b specific 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. Known hypersensitivity to any of the treatments or excipients
7. Second malignancy
8. Pregnant or breastfeeding women
9. Urinary outflow obstruction that cannot be relieved prior to starting treatment
10. Active inflammation of the urinary bladder (cystitis)

CT1a and CT1b specific 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. Known hypersensitivity to any of the treatments or excipients
6. Second malignancy
7. Pregnant or breastfeeding women
8. Urinary outflow obstruction that cannot be relieved prior to starting treatment
9. Active inflammation of the urinary bladder (cystitis)

Radiotherapy specific exclusion
1. Prior allo- or autologous Stem Cell Transplant
2. Second malignancy
3. Pregnant or breastfeeding women
4. Receiving radiotherapy as brachytherapy

CT2a and CT2b specific exclusion:
1. Prior allo- or autologous Stem Cell Transplant
2. Uncontrolled inter current illness or active infection
3. Second malignancy
4. Pregnant or breastfeeding women
5. Urinary outflow obstruction that cannot be relieved prior to starting treatment
6. Active inflammation of the urinary bladder (cystitis)

CT3 specific 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. Known hypersensitivity to any of the treatments or excipients
6. Second malignancy
7. Pregnant or breastfeeding women

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Event-free survival (EFS) – primary outcome measure for CT1A, CT1B, CT2A, CT2B, RT2, CT3. Time is measured as time from each registration/randomisation to first failure event (Relapse or progression of existing disease/occurrence of disease at new sites, death from any cause without disease progression, second malignant neoplasm) or time to last follow-up date if no events<br>2. Local failure free survival (LFFS) – primary outcome measure for RT1A, RT1B, RT1C, PET Substudy. Defined as time from randomisation to first local failure event (relapse or progression of tumour at the primary site at any time even if there has been a prior concurrent local, regional or distant failure), or time to last follow-up date if no events.