What clinical trials are available for children with rhabdomyosarcoma?

Clinical Trials Available for Children with Rhabdomyosarcoma

Currently, there are several active international clinical trials for children with rhabdomyosarcoma, with the most notable being FaR-RMS (NCT04625907) and trials investigating targeted agents like regorafenib in relapsed rhabdomyosarcoma. 1

Current Active Clinical Trials

Primary Trials for Newly Diagnosed Patients

• FaR-RMS (NCT04625907) - International trial studying:
  • Standard chemotherapy backbone
  • Maintenance chemotherapy (6-12 months for high-risk patients, 12-24 months for very high-risk patients)
  • Potential benefit of targeted agents 1

Trials for Relapsed/Refractory Disease

• Regorafenib trials - For relapsed RMS, investigating this targeted agent in combination with standard chemotherapy 1

Standard Treatment Backbone in Trials

Most trials incorporate the established chemotherapy backbone consisting of:

• Vincristine and dactinomycin with either:
  • Cyclophosphamide (VAC regimen)
  • Ifosfamide (IVA regimen) 2
• Dactinomycin is FDA-approved specifically for rhabdomyosarcoma as part of multi-phase, combination chemotherapy regimens 3

Trial Enrollment Considerations

Age-Specific Considerations

• AYA (Adolescent and Young Adult) patients with rhabdomyosarcoma have superior outcomes when treated with pediatric protocols 1
• Clinical trial enrollment decreases with age:
  • Ages 15-19: 5-34% enrollment rate
  • Ages 20-25: approximately 2% enrollment rate 1
• Pediatric cancer centers enroll more adolescents into clinical trials (35%) compared to adult cancer centers (12%) 1

Where to Access Trials

1. Specialized sarcoma centers - Treatment should be at centers with:

   • Extensive experience treating pediatric sarcomas
   • Access to supportive care services specific to pediatric/AYA population
   • Medical subspecialty services appropriate to sarcoma diagnosis 1

2. Pediatric cancer centers - Higher rate of trial enrollment (26%) compared to adult cancer centers (4%) 1

Important Trial Considerations

High-Dose Chemotherapy Trials

Some trials have investigated high-dose chemotherapy with autologous stem cell transplant (HDT/ASCT):

• No proven survival benefit for primary localized, metastatic, or relapsed rhabdomyosarcoma 1
• Prospective randomized trials are still needed to determine utility 1

Novel Approaches Being Studied

• Targeted therapies - Focus on molecular targets specific to rhabdomyosarcoma
• Maintenance therapy - Extended treatment periods (6-24 months) based on risk stratification 1
• Reduced radiation approaches - Response-adjusted radiation to reduce long-term effects 2

Pitfalls and Caveats

1. Low enrollment rates - One of the main reasons for lack of improvement in outcomes in AYA patients 1

2. Treatment toxicity considerations - Trials must balance:

   • Efficacy of treatment
   • Acute toxicities (myelosuppression, febrile neutropenia, hepatopathy)
   • Long-term effects (infertility, second malignancies) 2

3. Irinotecan trials - While being studied, caution is needed as:

   • Effectiveness in pediatric patients has not been established
   • A phase 2 trial of previously untreated rhabdomyosarcoma using irinotecan was halted due to high rate (28.6%) of progressive disease and early deaths (14%) 4

For optimal outcomes, all children with rhabdomyosarcoma should be enrolled in clinical trials whenever possible, as this rare tumor requires highly specialized care and important management questions remain to be answered 2.