FaR-RMS

Author:  CWS-Study group, Last modification: 2025/06/19 https://kinderkrebsinfo.de/doi/e283457

FaR-RMS An overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma
Disease Rhabdomyosarkoma
Type Prospective, international, multicentre trial: Phase 1b for new agents, Phase 3 for randomized questions
Rationale / Objectives

FaR-RMS is an over-arching study for patients with newly diagnosed and relapsed RMS including multi-arm, multi-stage questions with three principal aims. These are to evaluate:
• systemic therapy through the introduction of new agent regimens in the most advanced disease states: Very High Risk (VHR), High Risk (HR) and Relapse
• the duration of maintenance therapy
• radiotherapy to improve local control in VHR, HR and Standard Risk (SR) patients and to treat metastatic disease.
In addition the study will evaluate: risk stratification through the use of PAX-FOXO1 fusion gene status instead of histological subtyping.

Not all trial questions will be open to recruitment at any one time.

Therapy / Study arms

FaR-RMS is intended to be a rolling programme of research with new treatment arms being introduced dependant on emerging data and innovation, provided it is within the pre-defined research remit of the trial.
A maximum of three new arms will be added to each of the frontline (VHR and HR) and relapse randomisations; and a maximum of four new arms to the Phase 1b component.
An application for substantial amendment will be submitted to each competent authority for approval before addition of any new Investigational Medicinal Products (IMPs).

Phase I Dose Finding Studies
- To determine the recommended phase II dose (RP2D) of new systemic therapy regimens. The first combination to be tested is irinotecan in combination with ifosfamide, vincristine and actinomycin D (IRIVA).

Frontline Chemotherapy
To compare systemic therapy regimens for patients with VHR disease at diagnosis (CT1A).
- The first new combination regimens to be compared are IVADo and IRIVA in a dose intense schedule.
To compare new systemic therapy regimens with standard chemotherapy for patients with HR disease at diagnosis (CT1B). The standard chemotherapy is ifosfamide, vincristine, actinomycin D (IVA) (CT1B).
- The first new combination regime to be compared is irinotecan combined with IVA (IRIVA) in a dose intense schedule.

Radiotherapy (VHR, HR, SR)
- To determine whether pre-operative or standard post-operative radiotherapy is better for patients with resectable disease (RT1A).
- To determine whether dose escalation of radiotherapy improves the outcome in patients with a higher local failure risk (RT1B/C).
- To determine whether radiotherapy treatment of all sites of disease, including metastatic sites, when compared to radiotherapy treatment to the primary site and involved regional lymph nodes alone, improves the outcome for
    patients with unfavourable metastatic disease (RT2).

Maintenance Chemotherapy
- To determine whether the addition of a further 12 cycles of vinorelbine and cyclophosphamide (VnC) to standard 12 cycles of maintenance chemotherapy (i.e. 24 cycles total) improves the outcome for patients with VHR disease at diagnosis (CT2A).
- To determine whether the addition of a further 6 cycles of VnC (intravenous (i.v.) vinorelbine, oral cyclophosphamide) to the standard 6 cycles (i.e. 12 cycles total) improves the outcome for patients with localised HR disease at
    diagnosis (CT2B)

Relapsed RMS
- To determine whether new systemic therapy regimens improve event free survival in relapsed RMS compared to standard therapy (VIRT) (CT3): Initial new systemic therapy combination to be tested: Regorafenib (R) added to
    vincristine and irinotecan (VIR) (VIRR)

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

The eligibility for the different study arms should be checked in the actual protocol version.

Recruitment Frontline: A minimum of 840 patients with newly diagnosed RMS; Relapse: A minimum 260 patients with relapsed/recurrent RMS
Status Timeline: Start: 2025, Recruitment over 7 years, additional observation phase 3-6 years
EudraCT 2018-000515-24
Entry Study Register ClinicalTrials.gov: NCTNCT04625907
Principal Investigator Prof. Dr. med. M. Sparber-Sauer for Germany
Contact

Principal Investigator Germany

Prof. Dr. med. Monika Sparber-Sauer Olgahospital Kinder- und Jugendmedizin Kriegsbergstr. 62 70174 Stuttgart Telefon +49 (0) 711 278 73 870 m.sparber@klinikum-stuttgart.de

Documentation and Datamanagement

CWS-Studiendokumentation Klinikum Stuttgart - Standort Mitte (Olgahospital) Klinik für Kinder,- Jugend- und Frauenmedizin, Pädiatrie 5 Kriegsbergstr. 62 70174 Stuttgart Telefon +49 (711) 992 3870 Fax +49 (711) 992 2749 cws@klinikum-stuttgart.de

Sponsoring Coordinating Sponsor: University of Birmingham