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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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 Summary: 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.
Sponsor: St. Jude Children's Research Hospital

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

To estimate event-free survival for intermediate risk participants treated by vincristine-dactinomycin-cyclophosphamide (VAC) with the addition of maintenance anti-angiogenic therapy


Original Primary Outcome: Event-free survival [ Time Frame: 2 years after patient enrollment ]

To estimate event-free survival for intermediate risk participants treated by vincristine-dactinomycin-cyclophosphamide (VAC) with the addition of maintenance anti-angiogenic therapy


Current Secondary Outcome:

  • Event-free survival (high risk arm) [ Time Frame: 5 years after last high-risk arm enrollment ]
    To estimate event-free survival for high risk participants.
  • Rate of false negative and false positive the sentinel lymph node procedure (low and intermediate risk arms) [ Time Frame: 2 years after last low or intermediate arm enrollment ]
    Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection.
  • Rate of false negative and false positive the sentinel lymph node procedure (high risk arm) [ Time Frame: 5 years after last high risk arm enrollment ]
    Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection.
  • Local failure rate (low and intermediate risk arms) [ Time Frame: 2 years after last low or intermediate risk arm enrollment ]
    Maintain a high local control rate in participants treated with surgery and / or limited volume proton and photon radiation without dose escalation
  • Local failure rate (high risk arm) [ Time Frame: 5 years after last high risk arm enrollment ]
    Maintain a high local control rate in participants treated with surgery and / or limited volume proton and photon radiation without dose escalation
  • Patterns of failure (low and intermediate risk arms) [ Time Frame: 2 years after last low or intermediate risk arm enrollment ]
    Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume
  • Patterns of failure (high risk arm) [ Time Frame: 5 years after last high risk arm enrollment ]
    Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume
  • Number of patients that complete all cycles of maintenance chemotherapy (intermediate risk arm) [ Time Frame: 2 years after last low or intermediate risk arm enrollment ]
    Establish the feasibility of delivering 4 cycles of maintenance antiangiogenic chemotherapy (bevacizumab / sorafenib / low dose cyclophosphamide) in intermediate risk patients following standard chemotherapy.
  • Number of patients that complete all cycles of maintenance chemotherapy (high risk arm) [ Time Frame: 5 years after last high risk arm enrollment ]
    Establish the feasibility of delivering 4 cycles of maintenance antiangiogenic chemotherapy (bevacizumab / sorafenib / low dose cyclophosphamide) in high risk patients following standard chemotherapy.
  • Incidence of CTC grade 3 and higher toxicities related to proton bream therapy (low and intermediate and high risk arms) [ Time Frame: 2 years after last enrollment ]
    Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.


Original Secondary Outcome:

  • Rate of false negative and false positive the sentinel lymph node procedure [ Time Frame: 2 years after patient enrollment ]
    Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection
  • Local failure rate [ Time Frame: 2 years after patient enrollment ]
    Maintain a high local control rate in participants treated with surgery and / or limited volume proton radiation without dose escalation
  • Patterns of failure [ Time Frame: 2 years after patient enrollment ]
    Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume
  • Number of patients that complete all cycles of maintenance chemotherapy [ Time Frame: 2 years after patient enrollment ]
    Establish the feasibility of delivering 6 cycles of maintenance antiangiogenic chemotherapy (bevacizumab / sorafenib / low dose cyclophosphamide) in intermediate risk patients following standard chemotherapy.
  • Incidence of CTC grade 3 and higher toxicities related to proton bream therapy [ Time Frame: 2 years after patient enrollment ]
    Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.


Information By: St. Jude Children's Research Hospital

Dates:
Date Received: May 30, 2013
Date Started: December 4, 2013
Date Completion: June 30, 2021
Last Updated: April 25, 2017
Last Verified: January 2017