FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma

Sponsor
University of Birmingham
Study ID
NCT04625907
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Rhabdomyosarcoma

Eligibility Criteria

Sex
ALL
Age
N/A - N/A
Healthy Volunteers
Not accepted

Interventions

  • Irinotecan — DRUG
    antineoplastic enzyme inhibitor
  • Actinomycin D — DRUG
    Antineoplastic agent that is a polypeptide antibiotic
  • Doxorubicin — DRUG
    An anthracycline topoisomerase inhibitor isolated from streptpmyces peucetius var. casesius
  • Ifosfamide — DRUG
    chemotherapeutic agent chemically related to the nitrogen mustards and is a synthetic analog of cyclophosphamide
  • Vincristine — DRUG
    anti neoplastic vinca alkaloid agent
  • Vinorelbine — DRUG
    vinca alkaloid with a role as an antineoplastic agent
  • Cyclophosphamide — DRUG
    Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent
  • Temozolomide — DRUG
    oral antineoplastic alkylating agent
  • radiotherapy — RADIATION
    Ionising radiation
  • Regorafenib — DRUG
    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).

Study Details

FaR-RMS is an over-arching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS)

Key Dates

Start date
Sep 17, 2020
Status verified
May 2024
Primary completion
Jun 30, 2030
Completion
Jun 30, 2030

Study Design

Enrollment
1,672 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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.

Primary Outcome Measure

Event Free Survival (RT2) [ Time Frame: From randomisation to first failure event, timeframe 36 months ]

Central Contacts

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