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

Part of paid clinical trials in Jacksonville, Florida.

Sponsor
St. Jude Children's Research Hospital
Study ID
NCT01871766
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Rhabdomyosarcoma

Eligibility Criteria

Sex
ALL
Age
N/A - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Vincristine — DRUG
    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.
  • Dactinomycin — DRUG
    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.
  • Cyclophosphamide — DRUG
    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)
  • Surgical Resection — PROCEDURE
    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.
  • Radiation — PROCEDURE
    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.
  • Bevacizumab — DRUG
    Dosage and route of administration: 15 mg/kg/dose/day IV.
  • Sorafenib — DRUG
    Dosage and route of administration: 90 mg/m\^2/dose twice daily.
  • Myeloid Growth Factor — DRUG
    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.
  • Lymph Node Sampling — PROCEDURE
    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.
  • Irinotecan — DRUG
    Dosage and Route Administration: During interval compressed therapy - irinotecan 50mg/m\^2 IV (maximum dose 100 mg/day) daily x 5.
  • Ifosfamide — DRUG
    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.
  • Etoposide — DRUG
    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
  • Etoposide Phosphate — DRUG
    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.
  • Doxorubicin — DRUG
    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.
  • Dexrazoxane — DRUG
    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.
  • ^1^1C-methionine — DRUG
    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.

Study Details

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.

Key Dates

Start date
Dec 4, 2013
Status verified
Apr 2026
Primary completion
Dec 31, 2026
Completion
Jun 30, 2030

Study Design

Enrollment
115 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Low-Risk, Subset 1
    Lymph node sampling will take place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin and cyclophosphamide). They are then evaluated to determine how the tumor responded to treatment. Twelve additional weeks of chemotherapy (vincristine and dactinomycin) is given, followed by evaluation for tumor response. No further treatment is given, and participants are observed closely. Myeloid growth factor is given if needed. Participants also receive \^1\^1C-methionine as described in the intervention section.
  • Experimental: Low-Risk, Subset 2
    Lymph node sampling will take place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide). The tumor is evaluated to determine how it responded to treatment. Radiation therapy and/or surgical resection is performed to destroy or remove the remaining tumor. Twelve additional weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) is given, followed by evaluation for tumor response. If delayed for medical reasons, radiation therapy and/or surgical resection is done at this time. Participants then receive 16 weeks of additional chemotherapy (vincristine, dactinomycin and cyclophosphamide). No further treatment is given, and participants are observed closely. Myeloid growth factor will be given if needed. Participants also receive \^1\^1C-methionine as described in the intervention section.
  • Experimental: Intermediate-Risk
    Lymph node sampling takes place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide). The tumor is evaluated for treatment response. Radiation therapy and/or surgical resection is done. Twelve weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) is followed by evaluation for tumor response. If delayed for medical reasons, radiation therapy and/or surgical resection is done at this time. Participants receive 16 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) followed by 12 weeks of maintenance treatment (bevacizumab, sorafenib, oral cyclophosphamide). No further treatment is given, and participants are observed closely. Myeloid growth factor is given if needed. Participants also receive \^1\^1C-methionine as described in the intervention section.
  • Experimental: High-Risk
    Lymph node sampling takes place pretreatment and pre-surgery. Participants receive 6 weeks (2 cycles) chemotherapy (vincristine and irinotecan). The tumor is evaluated for treatment response. 3 cycles of chemotherapy \[vincristine, doxorubicin, cyclophosphamide/ifosfamide, etoposide (or etoposide phosphate) (VDC/IE)\] are given. Dexrazoxane is given prior to each dose of doxorubicin. Radiation therapy begins at week 4 or 20 (depending on tumor location) while receiving vincristine and irinotecan. 2 cycles of VDC/IE, 4 cycles of modified vincristine, dactinomycin, cyclophosphamide (VAC), then 2 cycles of modified vincristine/irinotecan (total of 54 weeks). High risk participants also receive additional maintenance therapy beginning week 55 with anti-angiogenic chemotherapy (bevacizumab, sorafenib, cyclophosphamide). Myeloid growth factor is given as needed. Participants also receive \^1\^1C-methionine as described in the intervention section.

Primary Outcome Measure

Event-free survival (intermediate risk arm) [ Time Frame: 2 years after last intermediate risk arm enrollment ]

Locations (4)

FacilityCityStateZIPSite coordinators
Nemours Children's ClinicJacksonvilleFlorida32207-
University of Florida Proton Therapy InstituteJacksonvilleFlorida32206-
St. Jude Children's Research HospitalMemphisTennessee38105-
Cook Children's Medical CenterFort WorthTexas76104-

Find similar trials in Jacksonville, FL

By research site
Nemours Children's Clinic· Jacksonville, FLUniversity of Florida Proton Therapy Institute· Jacksonville, FLSt. Jude Children's Research Hospital· Memphis, TNCook Children's Medical Center· Fort Worth, TX

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