Rhabdomyosarcoma (RMS) Clinical Trials

About Rhabdomyosarcoma (RMS) trials

Rhabdomyosarcoma (RMS) trial design turns on histologic subtype, fusion status, and risk group, primarily through pediatric cooperative-group networks. The two main histologic subtypes are embryonal RMS (ERMS, more common, generally better prognosis) and alveolar RMS (ARMS). About 60-70% of alveolar RMS carries a PAX3-FOXO1 or PAX7-FOXO1 gene fusion. Fusion testing evaluates both partner genes (FOXO1 and the PAX partner) and is the primary lab assay for assigning fusion status. Fusion-positive alveolar RMS is more aggressive than fusion-negative alveolar RMS, which clinically behaves more like embryonal RMS. FGFR4 mutations occur in some RMS tumors and gate emerging FGFR4-targeted trials. PD-L1 (CD274) status is tested but immunotherapy has historically had limited activity in RMS, with trials testing combinations to extend any benefit.

Front-line trials run primarily through the Children's Oncology Group (COG) and similar networks, testing risk-stratified VAC (vincristine, actinomycin-D, cyclophosphamide) and VI (vincristine, irinotecan) backbone modifications. Risk groups (low, intermediate, high, metastatic) determine treatment intensity, and each has its own trial set with stratification by stage, age, histology, and fusion status. Fusion-status-specific trials test treatment intensification for fusion-positive ARMS (which carries higher relapse risk) and de-escalation for fusion-negative ARMS (which behaves more like embryonal RMS). R/R trials test salvage chemotherapy combinations (vinorelbine, ifosfamide-based, irinotecan-based), targeted approaches for FGFR4-altered tumors, and emerging immunotherapy combinations including cellular therapy. Adult RMS trials are smaller in number and often separate from pediatric cooperative-group trials, although some pediatric protocols accept adolescents and young adults.

Most RMS trials screen on histologic subtype, fusion status, age, and prior chemotherapy. Subtype (embryonal vs alveolar vs other rare variants like spindle cell or pleomorphic) by central pathology review is foundational because most trials are subtype-restricted. Fusion status (PAX3-FOXO1, PAX7-FOXO1, or fusion-negative) is increasingly required for trial assignment because of its prognostic and predictive significance. Risk group classification by COG criteria (combining stage, group, age, histology, and fusion status). Age cutoffs vary by trial: pediatric cooperative-group trials typically enroll patients up to age 18 or 21, with some adolescent / young adult expansions, and adult RMS trials enroll separately. Prior VAC or VI chemotherapy and which lines define eligibility for R/R trials. Prior radiation therapy and the radiation field matter for trials testing radiation additions or for patients with prior radiated sites. Performance status using Lansky scale for younger pediatric patients or Karnofsky / ECOG for older patients.

Biomarkers tested in Rhabdomyosarcoma (RMS) trials

These are the molecular markers most commonly required or evaluated in Rhabdomyosarcoma (RMS) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.