Trial record 2 of 3 for:    rhabdomyosarcoma and bevacizumab

Treatment of Localized Rhabdomyosarcoma With Chemotherapy, Radiotherapy, and Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by St. Jude Children's Research Hospital
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01871766
First received: May 30, 2013
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

This study will treat participants with newly diagnosed, localized rhabdomyosarcoma (RMS) using chemotherapy, surgery and radiation.

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 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 6 cycles of maintenance anti-angiogenic chemotherapy in intermediate risk patients following standard chemotherapy.
  • Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.

Condition Intervention Phase
Rhabdomyosarcoma
Drug: Vincristine
Drug: Dactinomycin
Drug: Cyclophosphamide
Procedure: Surgical Resection
Procedure: Radiation
Drug: Bevacizumab
Drug: Sorafenib
Drug: Myeloid Growth Factor
Procedure: Lymph Node Sampling
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low and Intermediate Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: 2 years after patient enrollment ] [ Designated as safety issue: No ]
    To estimate event-free survival for intermediate risk participants treated by vincristine-dactinomycin-cyclophosphamide (VAC) with the addition of maintenance anti-angiogenic therapy


Secondary Outcome Measures:
  • Rate of false negative and false positive the sentinel lymph node procedure [ Time Frame: 2 years after patient enrollment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.


Estimated Enrollment: 48
Study Start Date: June 2013
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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/m2 IV. Maximum dose 2 mg in all participants.
Other Name: Oncovin(R)
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.
Other Names:
  • Actinomycin-D
  • Cosmegen(R)
Drug: Cyclophosphamide

Dosage and route of administration:

During VAC chemotherapy:

  • < 3 years of age = 40 mg/kg IV
  • > 3 years of age = 1200 mg/m2 IV, with MESNA.

During maintenance for intermediate-risk participants:

  • oral cyclophosphamide 50 mg/m2/dose/day (liquid or tablet)
Other Name: Cytoxan(R)
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.
Other Name: Surgery
Procedure: Radiation
Radiation therapy will be delivered at approximately week 13 after initiation of chemotherapy.
Other Names:
  • Proton Beam Radiation
  • External Beam Radiation
  • Brachytherapy
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.
Other Name: G-CSF
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.
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.
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/m2 IV. Maximum dose 2 mg in all participants.
Other Name: Oncovin(R)
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.
Other Names:
  • Actinomycin-D
  • Cosmegen(R)
Drug: Cyclophosphamide

Dosage and route of administration:

During VAC chemotherapy:

  • < 3 years of age = 40 mg/kg IV
  • > 3 years of age = 1200 mg/m2 IV, with MESNA.

During maintenance for intermediate-risk participants:

  • oral cyclophosphamide 50 mg/m2/dose/day (liquid or tablet)
Other Name: Cytoxan(R)
Procedure: Radiation
Radiation therapy will be delivered at approximately week 13 after initiation of chemotherapy.
Other Names:
  • Proton Beam Radiation
  • External Beam Radiation
  • Brachytherapy
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.
Other Name: G-CSF
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.
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 18 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.
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/m2 IV. Maximum dose 2 mg in all participants.
Other Name: Oncovin(R)
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.
Other Names:
  • Actinomycin-D
  • Cosmegen(R)
Drug: Cyclophosphamide

Dosage and route of administration:

During VAC chemotherapy:

  • < 3 years of age = 40 mg/kg IV
  • > 3 years of age = 1200 mg/m2 IV, with MESNA.

During maintenance for intermediate-risk participants:

  • oral cyclophosphamide 50 mg/m2/dose/day (liquid or tablet)
Other Name: Cytoxan(R)
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.
Other Name: Surgery
Procedure: Radiation
Radiation therapy will be delivered at approximately week 13 after initiation of chemotherapy.
Other Names:
  • Proton Beam Radiation
  • External Beam Radiation
  • Brachytherapy
Drug: Bevacizumab
Dosage and route of administration: 15 mg/kg/dose/day IV.
Other Names:
  • rhuMab
  • VEGF
  • Avastin(R)
Drug: Sorafenib
Dosage and route of administration: 90 mg/m2/dose twice daily.
Other Name: Nexavar(R)
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.
Other Name: G-CSF
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.

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. Low-risk (subset 2) and intermediate-risk participants will chemotherapy and receive radiation and/or undergo surgery to destroy/remove the tumor. Intermediate-risk participants will also receive 16 weeks of maintenance chemotherapy.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed, previously untreated participants with localized rhabdomyosarcoma (RMS).
  • Must have either low- or intermediate-risk disease, defined as:

    • Low-risk: Embryonal, botryoid, spindle cell tumors only (Subset 1: Stage 1, Group I; Stage 1 Group I; Stage 1 Group III orbital only; Stage 2 Group I; Stage 2 Group II) (Subset 2: Stage 1 Group III non orbit; Stage 3 Group I, II)
    • Intermediate-risk: Embryonal, botryoid, or spindle cell RMS: Stage 2 or 3 and Group III; Alveolar, undifferentiated, or anaplastic RMS: stage 1-3, group I-I; I)
  • Age < 22 years (eligible until 22nd birthday)
  • Performance level corresponding to ECOG score of 0, 1, or 2. The Lansky performance score should be used for participants < 16 years
  • Participant has received no prior radiotherapy or chemotherapy (excluding steroids). Prior biopsy, surgical resection and lymph node sampling is allowed.
  • Initiation of chemotherapy is planned within 6 weeks (42 days) of the definitive biopsy or surgical resection.
  • Adequate bone marrow function defined as:

    • Peripheral absolute neutrophil count (ANC) ≥ 750/μL
    • Platelet count ≥ 75,000/μL (transfusion independent)
  • Adequate liver function defined as total bilirubin < 1.5 x upper limit of normal (ULN) for age. Participants with biliary or hepatic primaries with bilirubin values greater than 1.5 x ULN may be enrolled on study if all other eligibility criteria are met.
  • Adequate renal function defined as:

    • Creatinine clearance or radioisotope GFR > 70 mL/min/1.732 or
    • Serum creatinine based on age and gender
    • Participants with urinary tract obstruction by tumor must meet the renal function criteria listed above AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract.
  • Females of child-bearing potential cannot be pregnant or breast-feeding. Female participants > 10 years of age or post-menarchal must have a negative serum or urine pregnancy test within 24 hours prior to beginning treatment. Female participants who are breast feeding must agree to stop breast feeding.
  • Sexually active patients of childbearing potential must be willing to use effective contraception during therapy and for at least 1 month after treatment is completed.
  • No evidence of active, uncontrolled infection.
  • All participants and/or their parents or legal guardians must sign a written informed consent.

Exclusion Criteria:

  • Participants who fail to meet one or more of the inclusion criteria will be excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01871766

Contacts
Contact: Matthew J. Krasin, MD 866-278-5833 info@stjude.org

Locations
United States, Florida
University of Florida Proton Therapy Institute Recruiting
Jacksonville, Florida, United States, 32206
Contact: Daniel J. Indelicato, MD    904-588-2442      
Principal Investigator: Daniel J. Indelicato, MD         
Nemours Childrens Clinic Recruiting
Jacksonville, Florida, United States, 32207
Contact: Eric S. Sandler, MD    904-697-3600      
Principal Investigator: Eric S. Sandler, MD         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Matthew J. Krasin, MD    866-278-5833    Info@stjude.org   
Principal Investigator: Matthew J. Krasin, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Matthew J. Krasin, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01871766     History of Changes
Other Study ID Numbers: RMS13
Study First Received: May 30, 2013
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Rhabdomyosarcoma
Radiation therapy
Proton beam

Additional relevant MeSH terms:
Rhabdomyosarcoma
Bevacizumab
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Sorafenib
Cyclophosphamide
Vincristine
Dactinomycin
Mitogens
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014