Skip to content
Triangle logo TriangleGet started
← Study library

NCT05304585 · CITED IN SOURCE DOCUMENTS

Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
RECRUITING
Registry last update
2026-08-25

Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial). * Patients must be =\< 21 years at the time of enrollment. * Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients. * All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed. * Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease. * Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease. * Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients \>= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging. * Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors. * Clinically or radiographically enlarged nodes must be sampled for histologic evaluation. * Patients must have a Lansky (for patients =\< 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of \>= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score. * Peripheral absolute neutrophil count (ANC) \>= 750/uL (within 7 days prior to enrollment). * Platelet count \>= 75,000/uL (transfusion independent) (within 7 days prior to enrollment). * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows: * Age: 1 month to \< 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female) * Age: 6 months to \< 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female) * Age: 1 to \< 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female) * Age: 2 to \< 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female) * Age: 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female) * Age: 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2 (female) * Age: 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4 (female) * Age \>= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and * If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age. * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L. * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L * If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L * All patients and/or their parents or legal guardians must sign a written informed consent. * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met. Exclusion Criteria: * Patients who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted. * Patients who have received chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy. * Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment. * Patients unable to undergo radiation therapy, if necessary, as specified in the protocol. * Evidence of uncontrolled infection. * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential. * Lactating females who plan to breastfeed their infants. * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
healthy Volunteers
false
maximum Age
21 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 2-4, 7-8, and 11-12 and dactinomycin IV over 1-5 minutes or 10-15 minutes on day 1 of cycles 2-5 and 8-14. Patients also receive cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 12-13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo radiation therapy at cycle 5. Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.
    intervention Names
    1. Procedure: Biopsy Procedure
    2. Procedure: Bone Scan
    3. Procedure: Computed Tomography
    4. Drug: Cyclophosphamide
    5. Biological: Dactinomycin
    6. Procedure: Magnetic Resonance Elastography
    7. Procedure: Positron Emission Tomography
    8. Radiation: Radiation Therapy
    9. Drug: Vincristine
    label
    Regimen M (positive mutation)
    type
    EXPERIMENTAL
  2. description
    Patients with VLR RMS receive vincristine intravenously (IV) on day 1 of each cycle and days 8 and 15 of cycles 1, 3, 5, and 7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.
    intervention Names
    1. Procedure: Biopsy Procedure
    2. Procedure: Bone Scan
    3. Biological: Dactinomycin
    4. Procedure: Magnetic Resonance Elastography
    5. Procedure: Positron Emission Tomography
    6. Drug: Vincristine
    label
    Regimen VA (VLR RMS)
    type
    EXPERIMENTAL
  3. description
    Patients with LR RMS receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 1-3. Patients also receive dactinomycin IV over 1-5 minutes or 10-15 minutes and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 5-7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Radiation therapy (if needed) will be administered at cycle 5.Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.
    intervention Names
    1. Procedure: Biopsy Procedure
    2. Procedure: Bone Scan
    3. Procedure: Computed Tomography
    4. Drug: Cyclophosphamide
    5. Biological: Dactinomycin
    6. Procedure: Magnetic Resonance Elastography
    7. Procedure: Positron Emission Tomography
    8. Drug: Vincristine
    label
    Regimen VAC/VA (VL RMS)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Regimen M (positive mutation)
    2. Regimen VA (VLR RMS)
    3. Regimen VAC/VA (VL RMS)
    description
    Undergo tumor biopsy
    name
    Biopsy Procedure
    other Names
    1. Biopsy
    2. BIOPSY_TYPE
    3. Bx
    type
    PROCEDURE
  2. arm Group Labels
    1. Regimen M (positive mutation)
    2. Regimen VA (VLR RMS)
    3. Regimen VAC/VA (VL RMS)
    description
    Undergo bone scan
    name
    Bone Scan
    other Names
    1. Bone Scintigraphy
    type
    PROCEDURE
  3. arm Group Labels
    1. Regimen M (positive mutation)
    2. Regimen VAC/VA (VL RMS)
    description
    Undergo CT scan
    name
    Computed Tomography
    other Names
    1. CAT
    2. CAT Scan
    3. Computed Axial Tomography
    4. Computerized Axial Tomography
    5. Computerized axial tomography (procedure)
    6. Computerized Tomography
    7. Computerized Tomography (CT) scan
    8. CT
    9. CT Scan
    10. Diagnostic CAT Scan
    11. Diagnostic CAT Scan Service Type
    12. tomography
    type
    PROCEDURE
  4. arm Group Labels
    1. Regimen M (positive mutation)
    2. Regimen VAC/VA (VL RMS)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Asta B 518
    4. B 518
    5. B-518
    6. B518
    7. Carloxan
    8. Ciclofosfamida
    9. Ciclofosfamide
    10. Cicloxal
    11. Clafen
    12. Claphene
    type
    DRUG
  5. arm Group Labels
    1. Regimen M (positive mutation)
    2. Regimen VA (VLR RMS)
    3. Regimen VAC/VA (VL RMS)
    description
    Given IV
    name
    Dactinomycin
    other Names
    1. Actinomycin A IV
    2. Actinomycin C1
    3. Actinomycin D
    4. Actinomycin I1
    5. Actinomycin IV
    6. Actinomycin X 1
    7. Actinomycin-[thr-val-pro-sar-meval]
    8. Cosmegen
    9. DACT
    10. Dactinomycine
    11. Lyovac Cosmegen
    12. Meractinomycin
    type
    BIOLOGICAL
  6. arm Group Labels
    1. Regimen M (positive mutation)
    2. Regimen VA (VLR RMS)
    3. Regimen VAC/VA (VL RMS)
    description
    Undergo MRI
    name
    Magnetic Resonance Elastography
    other Names
    1. MRE
    type
    PROCEDURE
  7. arm Group Labels
    1. Regimen M (positive mutation)
    2. Regimen VA (VLR RMS)
    3. Regimen VAC/VA (VL RMS)
    description
    Undergo PET scan
    name
    Positron Emission Tomography
    other Names
    1. Medical Imaging, Positron Emission Tomography
    2. PET
    3. PET Scan
    4. Positron emission tomography (procedure)
    5. Positron Emission Tomography Scan
    6. Positron-Emission Tomography
    7. PT
    type
    PROCEDURE
  8. arm Group Labels
    1. Regimen M (positive mutation)
    description
    Undergo radiation
    name
    Radiation Therapy
    other Names
    1. Cancer Radiotherapy
    2. Energy Type
    3. ENERGY_TYPE
    4. Irradiate
    5. Irradiated
    6. Irradiation
    7. Radiation
    8. Radiation Therapy, NOS
    9. Radiotherapeutics
    10. Radiotherapy
    11. RT
    12. Therapy, Radiation
    type
    RADIATION
  9. arm Group Labels
    1. Regimen M (positive mutation)
    2. Regimen VA (VLR RMS)
    3. Regimen VAC/VA (VL RMS)
    description
    Given IV
    name
    Vincristine
    other Names
    1. LCR
    2. Leurocristine
    3. VCR
    4. Vincrystine
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
205
type
ESTIMATED
Registered outcome plans (not posted results)
other Outcomes
  1. description
    Summary statistics will be used to describe the methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma. Correlation between methylation patterns and clinical presentation, histology, and genetics will be evaluated.
    measure
    Methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma
    time Frame
    Up to 5 years
  2. description
    Summary statistics will be used to provide a descriptive analysis of patients treated on Regimen M, including patient demographics, clinical characteristics and outcomes.
    measure
    Descriptive analysis of patients treated on Regimen M
    time Frame
    Up to 5 years
primary Outcomes
  1. description
    The Kaplan-Meier method will be used to estimate 3-year FFS along with 80% log-minus-log transformed confidence limits for very low risk (VLR) patients.
    measure
    Failure free survival (FFS) for very low risk patients
    time Frame
    From study enrollment to disease progression, recurrence, or death as a first event, assessed up to 3 years
  2. description
    The Kaplan-Meier method will be used to estimate 3 year FFS along with 80% log-minus-log transformed confidence limits for low risk (LR) patients.
    measure
    Failure free survival (FFS) for low risk patients
    time Frame
    From study enrollment to disease progression, recurrence, or death as a first event, assessed up to 3 years
secondary Outcomes
  1. description
    Log-rank test will be used to compare the OS of patients with VLR rhabdomyosarcoma (RMS) treated with 24 weeks of vincristine, dactinomycin (VA) to the VLR RMS patients from ARST0331 and D9602 with the same inclusion criteria.
    measure
    Overall survival (OS) for very low risk patients
    time Frame
    From study entry to death of any cause, assessed up to 5 years
  2. description
    Log-rank test will be used to compare the OS from LR RMS patients to LR RMS patients from ARST0331 and D9602 with the same inclusion criteria.
    measure
    Overall survival (OS) for low risk patients
    time Frame
    From study entry to death of any cause, assessed up to 5 years
  3. description
    If the percentage of patients who have molecular testing results returned by 6 weeks is \>= 80% then the central molecular risk stratification is considered feasible.
    measure
    Feasibility of central molecular risk stratification of patients assessed by the percentage of patients who have molecular testing results returned by 6 weeks
    time Frame
    Up to 24 weeks
Full study description
brief Summary
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.
detailed Description
PRIMARY OBJECTIVES: I. To evaluate the failure free survival (FFS) of patients with very low-risk (VLR) rhabdomyosarcoma (RMS) (fusion negative \[FN\], stage 1, clinical group \[CG\] I, MYOD1 wildtype \[WT\], TP53 \[WT\]) when treated with 24 weeks of vincristine and dactinomycin (VA). II. To evaluate the FFS of patients with low-risk (LR) RMS (FN, stage 1 CG II, or stage 2 CG I/II or CG III \[orbit only\], MYOD1 WT, TP53 WT) when treated with 12 weeks of vincristine, dactinomycin and cyclophosphamide (VAC) followed by 12 weeks of VA. SECONDARY OBJECTIVES: I. To evaluate the overall survival (OS) of patients with VLR RMS treated with 24 weeks of VA. II. To evaluate the OS of patients with LR RMS treated with 12 weeks of VAC followed by 12 weeks of VA. III. To demonstrate the feasibility of central molecular risk stratification of patients with newly diagnosed RMS in the context of a prospective clinical trial. EXPLORATORY OBJECTIVES: I. To collect blood and tissue samples for banking at baseline, during treatment, at the end of therapy, and at the time of progression to bank for future research. II. To describe the methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma. III. To describe the outcomes of patients with VLR or LR RMS and MYOD1 or TP53 mutations treated with intensified therapy. OUTLINE: Patients are assigned to 1 of 2 regimens based on clinical features. Patients with positive mutation status are transitioned to a third regimen, Regimen M. REGIMEN VA: Patients with VLR RMS receive vincristine intravenously (IV) on day 1 of each cycle and days 8 and 15 of cycles 1, 3, 5, and 7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). REGIMEN VAC/VA: Patients with LR RMS receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 1-3. Patients also receive dactinomycin IV over 1-5 minutes or 10-15 minutes and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 5-7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Patients may also undergo radiation therapy at cycle 5. REGIMEN M: Patients receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 2-4, 7-8, and 11-12 and dactinomycin IV over 1-5 minutes or 10-15 minutes on day 1 of cycles 2-5 and 8-14. Patients also receive cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 12-13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo radiation therapy at cycle 5. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan, positron emission tomography (PET) scan and tumor biopsy throughout the study.
Source references
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-18da0956a925b725dc7c
      requested nct id
      NCT05304585
      primary nct id
      NCT05304585
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      3e253a588554150bd5ae5ac665bdef96fb4f453120bd18f9dde0221d2dbf3739
      payload sha256
      c5ba3387921b0d0f99d6afdff14adc7eab80eeb9a4a212823d428752ef0126a6
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-18da0956a925b725dc7c
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT05304585
      occurrences
      1. context exact
        /or institutional clinical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1875"><li><strong><a href="/clinicaltrials/NCT05304585">ARST2032 (NCT05304585)</a></strong> (Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low-Risk, Fusion-Negative Rhabdomyosarc
        end
        400632
        exact text
        NCT05304585
        start
        400621
      2. context exact
        cal trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1875"><li><strong><a href="/clinicaltrials/NCT05304585">ARST2032 (NCT05304585)</a></strong> (Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low-Risk, Fusion-Negative Rhabdomyosarcoma)<strong>:</strong>
        end
        400655
        exact text
        NCT05304585
        start
        400644
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/63d8e64beb9c88f092.html
      source file sha256
      3e253a588554150bd5ae5ac665bdef96fb4f453120bd18f9dde0221d2dbf3739
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:20.508284+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      6f71654db32394dcd1834a8ce9f674ddb7f238c7b083f23eec93a3611ef198a7
      source title
      Childhood Rhabdomyosarcoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 11, 2025
        datetime
        2025-04-11T12:00:00Z
        display
        April 11, 2025

    Preserved source evidence · Not medical advice