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RhabdomyosarcomaPhase 2NCT01871766

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

A Phase 2 study testing Vincristine, Dactinomycin and Cyclophosphamide in people with Rhabdomyosarcoma, run by St. Jude Children's Research Hospital at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 21 years
Conditions the study is for
Rhabdomyosarcoma
What is being tested?
Vincristine, Dactinomycin and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
4 sitesUnited States
Study dates
4 Dec 2013to Jun 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Newly diagnosed participants with localized rhabdomyosarcoma (RMS).
  • Must have either low-, intermediate-, or high-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)
  • High-risk: Embryonal, botryoid, spindle cell, alveolar, undifferentiated, or anaplastic RMS with metastatic disease at diagnosis (stage 4).
  • Participants treated on this protocol in the low or intermediate risk arm who experience disease progression prior to week 13 will transfer to the high risk arm and proceed with high risk chemotherapy starting at week 1 of the protocol.
Show all 23Show fewer
  • 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 for rhabdomyosarcoma (excluding steroids) unless an emergency situation requires local tumor treatment. 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.
  • Patients requiring emergency radiation therapy are eligible for enrollment on this study.
  • 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.

Who cannot join

  • Participants who fail to meet one or more of the inclusion criteria will be excluded.
  • Inclusion Criteria for Contrast-Enhanced Ultrasound (CEUS) Sub-Study:
  • Newly diagnosis or suspected diagnosis of previously untreated participants with rhabdomyosarcoma (RMS). NOTE: Patients with suspected diagnosis of RMS may enroll on screening part of study but must have histologic diagnosis to enroll on treatment part of study.
  • Must have either intermediate-risk or high risk disease.
  • 0-21 years of age.
  • Undergoing upfront surgical resection of the primary tumor.
  • History of allergy to Optison(TM) contrast agent or blood products.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • University of Florida Proton Therapy Institute

    Jacksonville, Florida, 32206

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

Other trials in United States

About this study

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:

Read more
  • 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.
Read the 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.

Being tested
Vincristine, Dactinomycin, Cyclophosphamide, Surgical Resection, Radiation
Keywords
Rhabdomyosarcoma, Radiation therapy, Proton beam
Medical subject headings
Rhabdomyosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VincristineDrug

    Also called Oncovin®

    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.

  • DactinomycinDrug

    Also called Actinomycin-D, Cosmegen®

    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.

  • CyclophosphamideDrug

    Also called Cytoxan(R)

    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 ResectionProcedure or surgery

    Also called Surgery

    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.

  • RadiationProcedure or surgery

    Also called Proton Beam Radiation, External Beam Radiation, Brachytherapy

    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.

  • BevacizumabDrug

    Also called rhuMab, VEGF, Avastin®

    Dosage and route of administration: 15 mg/kg/dose/day IV.

  • SorafenibDrug

    Also called Nexavar®

    Dosage and route of administration: 90 mg/m^2/dose twice daily.

  • Myeloid Growth FactorDrug

    Also called G-CSF, Filgrastim, Pegfilgrastim

    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 SamplingProcedure or surgery

    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.

  • IrinotecanDrug

    Also called Camptosar ®

    Dosage and Route Administration: During interval compressed therapy - irinotecan 50mg/m^2 IV (maximum dose 100 mg/day) daily x 5.

  • IfosfamideDrug

    Also called Ifex ®

    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.

  • EtoposideDrug

    Also called VP-16, Vepesid®

    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 PhosphateDrug

    Also called Etopophos®

    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.

  • DoxorubicinDrug

    Also called Adriamycin®

    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.

  • DexrazoxaneDrug

    Also called Zinecard

    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-methionineDrug

    Also called Contrast Media

    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 groups in NCT01871766
Study groupRoleWhat they receive
Low-Risk, Subset 1ExperimentalLymph 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.
Receives: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Surgical Resection; Procedure: Radiation; Drug: Myeloid Growth Factor; Procedure: Lymph Node Sampling; Drug: ^1^1C-methionine
Low-Risk, Subset 2ExperimentalLymph 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.
Receives: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Radiation; Drug: Myeloid Growth Factor; Procedure: Lymph Node Sampling; Drug: ^1^1C-methionine
Intermediate-RiskExperimentalLymph 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.
Receives: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Surgical Resection; Procedure: Radiation; Drug: Bevacizumab; Drug: Sorafenib; Drug: Myeloid Growth Factor; Procedure: Lymph Node Sampling; Drug: ^1^1C-methionine
High-RiskExperimentalLymph 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.
Receives: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Surgical Resection; Procedure: Radiation; Drug: Bevacizumab; Drug: Sorafenib; Drug: Myeloid Growth Factor; Procedure: Lymph Node Sampling; Drug: Irinotecan; Drug: Ifosfamide; Drug: Etoposide; Drug: Etoposide Phosphate; Drug: Doxorubicin; Drug: Dexrazoxane; Drug: ^1^1C-methionine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival (intermediate risk arm)

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

    Measured: 2 years after last intermediate risk arm enrollment

Secondary outcomes (10)

  1. Event-free survival (high risk arm)

    To estimate event-free survival for high risk participants.

    Measured: 5 years after last high-risk arm enrollment

  2. Rate of false negative and false positive the sentinel lymph node procedure (low and intermediate risk arms)

    Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection.

    Measured: 2 years after last low or intermediate arm enrollment

  3. Rate of false negative and false positive the sentinel lymph node procedure (high risk arm)

    Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection.

    Measured: 5 years after last high risk arm enrollment

  4. Local failure rate (low and intermediate risk arms)

    Maintain a high local control rate in participants treated with surgery and / or limited volume proton and photon radiation without dose escalation

    Measured: 2 years after last low or intermediate risk arm enrollment

  5. Local failure rate (high risk arm)

    Maintain a high local control rate in participants treated with surgery and / or limited volume proton and photon radiation without dose escalation

    Measured: 5 years after last high risk arm enrollment

  6. Patterns of failure (low and intermediate risk arms)

    Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume

    Measured: 2 years after last low or intermediate risk arm enrollment

  7. Patterns of failure (high risk arm)

    Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume

    Measured: 5 years after last high risk arm enrollment

  8. Number of patients that complete all cycles of maintenance chemotherapy (intermediate risk arm)

    Establish the feasibility of delivering 4 cycles of maintenance antiangiogenic chemotherapy (bevacizumab / sorafenib / low dose cyclophosphamide) in intermediate risk patients following standard chemotherapy.

    Measured: 2 years after last low or intermediate risk arm enrollment

  9. Number of patients that complete all cycles of maintenance chemotherapy (high risk arm)

    Establish the feasibility of delivering 4 cycles of maintenance antiangiogenic chemotherapy (bevacizumab / sorafenib / low dose cyclophosphamide) in high risk patients following standard chemotherapy.

    Measured: 5 years after last high risk arm enrollment

  10. Incidence of CTC grade 3 and higher toxicities related to proton bream therapy (low and intermediate and high risk arms)

    Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.

    Measured: 2 years after last enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2013 (estimated)
  2. Study start4 Dec 2013
  3. Primary completionDec 2026 (estimated)
  4. Study completionJun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
115 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01871766
Sponsor's protocol ID
RMS13
Other IDs
NCI-2013-00913
Status last verified
Jun 2026
First submitted
30 May 2013
Last updated
17 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Patel AG, Chen X, Huang X, Clay MR, Komorova N, Krasin MJ, Pappo A, Tillman H, Orr BA, McEvoy J, Gordon B, Blankenship K, Reilly C, Zhou X, Norrie JL, Karlstrom A, Yu J, Wodarz D, Stewart E, Dyer MA. The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma. Dev Cell. 2022 May 23;57(10):1226-1240.e8. doi: 10.1016/j.devcel.2022.04.003. Epub 2022 Apr 27.

    PubMed 35483358

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vincristine, Dactinomycin and Cyclophosphamide in people with Rhabdomyosarcoma, run by St. Jude Children's Research Hospital at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (intermediate risk arm) (time frame: 2 years after last intermediate risk arm enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01871766, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.

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