NCT01871766

Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low, Intermediate and High Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 115 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

This study will treat participants with newly diagnosed, low, intermediate and high risk rhabdomyosarcoma (RMS) using multi-modality risk-adapted therapy with standard or intensified dose chemotherapy, radiation and surgical resection. Intermediate and high risk participants will receive an additional 12 weeks (4 cycles) of maintenance therapy with anti-angiogenic chemotherapy. PRIMARY OBJECTIVE: * Estimate event-free survival for intermediate risk participants treated with vincristine, dactinomycin and cyclophosphamide with the addition of maintenance anti-angiogenic therapy. SECONDARY OBJECTIVES: * Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection. * Maintain a high local control rate in participants treated with surgery and/or limited volume proton and photon radiation without dose escalation. * Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume. * Establish the feasibility of delivering 4 cycles of maintenance anti-angiogenic chemotherapy in intermediate and high risk patients following standard chemotherapy. * Estimate the event free survival for high risk patients receiving interval dose compressed therapy and maintenance anti-angiogenic therapy. * Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.

Detailed description

Participants will be stratified based on both a pretreatment staging system and a post-surgery surgico/pathologic clinical grouping system. Treatment for low-risk (subset 1) participants will consist of chemotherapy and radiation. Low-risk (subset 2) and intermediate-risk participants will receive chemotherapy and radiation and/or undergo surgery to destroy/remove the tumor. Intermediate-risk participants will also receive 16 weeks of maintenance chemotherapy. High-risk participants will receive chemotherapy and radiation therapy. High-risk participants will also receive additional maintenance therapy with anti-angiogenic chemotherapy.

Conditions

• Rhabdomyosarcoma

Interventions

Type	Name	Description
DRUG	Vincristine	Dosage and route of administration: * \< 1 year of age=0.025 mg/kg intravenously (IV) * \> 1 year and \< 3 years= 0.05 mg/kg IV * ≥ 3 years=1.5 mg/m\^2 IV. Maximum dose 2 mg in all participants.
DRUG	Dactinomycin	Dosage and route of administration: * \< 1 year=0.025 mg/kg IV push * ≥ 1 year=0.045 mg/kg IV push over 1 to 5 minutes.
DRUG	Cyclophosphamide	Dosage and route of administration: During VAC chemotherapy: * \< 3 years of age = 40 mg/kg IV * ≥ 3 years of age = 1200 mg/m\^2 IV, with MESNA. During maintenance for intermediate-risk participants: * oral cyclophosphamide 50 mg/m\^2/dose/day (liquid or tablet)
PROCEDURE	Surgical Resection	Surgery will be performed for the primary site tumor with the goal of removing tumor cells while maintaining function in the organ or adjacent organs involved.
PROCEDURE	Radiation	Radiation therapy will be delivered at approximately week 13 (intermediate risk) or week 19 (high risk) after initiation of chemotherapy. Certain patients will receive radiation at week 4.
DRUG	Bevacizumab	Dosage and route of administration: 15 mg/kg/dose/day IV.
DRUG	Sorafenib	Dosage and route of administration: 90 mg/m\^2/dose twice daily.
DRUG	Myeloid Growth Factor	If a participant's chemotherapy has been delayed or modified for hematologic toxicity, or if participant experiences a significant life-threatening toxicity due to bone marrow suppression, myeloid growth factor (either filgrastim or peg-filgrastim) will be given per institutional practice. High Risk participants receive filgrastim 5 micrograms/kg/day (maximum 300 micrograms) subcutaneously beginning 24-36 hours after the last dose of chemotherapy. Continue at least 7 days, or until the ANC ≥750/µL whichever comes last. Sargramostim or peg-filgrastim may not be used.
PROCEDURE	Lymph Node Sampling	Clinical and/or imaging evaluation of regional lymph nodes will be conducted pretreatment and preoperatively as part of staging. This will aid in determining the efficacy of this procedure in defining involved lymphatics in "at risk" patients.
DRUG	Irinotecan	Dosage and Route Administration: During interval compressed therapy - irinotecan 50mg/m\^2 IV (maximum dose 100 mg/day) daily x 5.
DRUG	Ifosfamide	Dosage and Route of Administration: During interval compressed therapy - Age \> 1 year: 1800 mg/m\^2/day IV x 5 Age \<1 year: treat with 50% doses calculated on a m\^2 basis.
DRUG	Etoposide	Dosage and Route of Administration: Age \>1 year 100 mg/m\^2/day IV x 5 Age \< 1 year treat with 50% doses calculated on a m\^2 basis
DRUG	Etoposide Phosphate	Dosage and Route of Administration: Used in substitution for etoposide in participants who experience allergic reaction. It will be administered 100 mg/m\^2/day IV.
DRUG	Doxorubicin	Dosage and route of Administration: Age ≥1 year, 37.5 mg/m\^2 IV over 1 hour x 2 days Age \<1 year, 18.75 mg/m\^2 (i.e., a 50% dose reduction) IV over 1 hour x 2 days.
DRUG	Dexrazoxane	Dosage and Route of Administration: Dexrazoxane dose should be 10x that of doxorubicin. Age ≥1 year, 375 mg/m\^2 IV over 15-30 minutes Age \<1 year, 187l.5 mg/m\^2 (i.e., a 50% dose reduction) IV over 15-30 minutes.
DRUG	^1^1C-methionine	Participants receive \^1\^1C-methionine to relate the distribution, intensity and change in \^1\^1C-methionine CTPET imaging of the primary site to tumor control and patient outcome.

Timeline

• Start date: 2013-12-04
• Primary completion: 2026-12-01
• Completion: 2030-06-01
• First posted: 2013-06-07
• Last updated: 2025-12-17

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study