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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05304585
Recruitment Status : Recruiting
First Posted : March 31, 2022
Last Update Posted : April 22, 2024
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

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.

Condition or disease Intervention/treatment Phase
Embryonal Rhabdomyosarcoma Fusion-Negative Alveolar Rhabdomyosarcoma Spindle Cell/Sclerosing Rhabdomyosarcoma Procedure: Biopsy Procedure: Bone Scan Procedure: Computed Tomography Drug: Cyclophosphamide Biological: Dactinomycin Procedure: Magnetic Resonance Elastography Procedure: Positron Emission Tomography Radiation: Radiation Therapy Drug: Vincristine Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 205 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Phase 3 Study of Patients With Newly Diagnosed Very Low-Risk and Low-Risk Fusion Negative Rhabdomyosarcoma
Actual Study Start Date : August 4, 2022
Estimated Primary Completion Date : December 31, 2030
Estimated Study Completion Date : December 31, 2030


Arm Intervention/treatment
Experimental: Regimen M (positive mutation)
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.
Procedure: Biopsy
Undergo tumor biopsy
Other Names:
  • BIOPSY_TYPE
  • Bx

Procedure: Bone Scan
Undergo bone scan
Other Name: Bone Scintigraphy

Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Asta B 518
  • B-518
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • WR-138719

Biological: Dactinomycin
Given IV
Other Names:
  • Actinomycin A IV
  • Actinomycin C1
  • Actinomycin D
  • Actinomycin I1
  • Actinomycin IV
  • Actinomycin X 1
  • Actinomycin-[thr-val-pro-sar-meval]
  • Cosmegen
  • DACT
  • Dactinomycine
  • Lyovac Cosmegen
  • Meractinomycin

Procedure: Magnetic Resonance Elastography
Undergo MRI
Other Name: MRE

Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron emission tomography (procedure)
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT

Radiation: Radiation Therapy
Undergo radiation
Other Names:
  • Cancer Radiotherapy
  • Energy Type
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation

Drug: Vincristine
Given IV
Other Names:
  • LCR
  • Leurocristine
  • VCR
  • Vincrystine

Experimental: Regimen VA (VLR RMS)
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.
Procedure: Biopsy
Undergo tumor biopsy
Other Names:
  • BIOPSY_TYPE
  • Bx

Procedure: Bone Scan
Undergo bone scan
Other Name: Bone Scintigraphy

Biological: Dactinomycin
Given IV
Other Names:
  • Actinomycin A IV
  • Actinomycin C1
  • Actinomycin D
  • Actinomycin I1
  • Actinomycin IV
  • Actinomycin X 1
  • Actinomycin-[thr-val-pro-sar-meval]
  • Cosmegen
  • DACT
  • Dactinomycine
  • Lyovac Cosmegen
  • Meractinomycin

Procedure: Magnetic Resonance Elastography
Undergo MRI
Other Name: MRE

Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron emission tomography (procedure)
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT

Drug: Vincristine
Given IV
Other Names:
  • LCR
  • Leurocristine
  • VCR
  • Vincrystine

Experimental: Regimen VAC/VA (VL RMS)
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.
Procedure: Biopsy
Undergo tumor biopsy
Other Names:
  • BIOPSY_TYPE
  • Bx

Procedure: Bone Scan
Undergo bone scan
Other Name: Bone Scintigraphy

Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Asta B 518
  • B-518
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • WR-138719

Biological: Dactinomycin
Given IV
Other Names:
  • Actinomycin A IV
  • Actinomycin C1
  • Actinomycin D
  • Actinomycin I1
  • Actinomycin IV
  • Actinomycin X 1
  • Actinomycin-[thr-val-pro-sar-meval]
  • Cosmegen
  • DACT
  • Dactinomycine
  • Lyovac Cosmegen
  • Meractinomycin

Procedure: Magnetic Resonance Elastography
Undergo MRI
Other Name: MRE

Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron emission tomography (procedure)
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT

Drug: Vincristine
Given IV
Other Names:
  • LCR
  • Leurocristine
  • VCR
  • Vincrystine




Primary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    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.


Secondary Outcome Measures :
  1. Overall survival (OS) for very low risk patients [ Time Frame: From study entry to death of any cause, assessed up to 5 years ]
    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.

  2. Overall survival (OS) for low risk patients [ Time Frame: From study entry to death of any cause, assessed up to 5 years ]
    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.

  3. 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 ]
    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.


Other Outcome Measures:
  1. Methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma [ Time Frame: Up to 5 years ]
    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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (within 7 days prior to enrollment).
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05304585


Locations
Show Show 151 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Josephine H Haduong Children's Oncology Group
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT05304585    
Other Study ID Numbers: ARST2032
NCI-2022-01012 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ARST2032 ( Other Identifier: Children's Oncology Group )
ARST2032 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Posted: March 31, 2022    Key Record Dates
Last Update Posted: April 22, 2024
Last Verified: April 2024

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Rhabdomyosarcoma
Rhabdomyosarcoma, Embryonal
Rhabdomyosarcoma, Alveolar
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Dactinomycin
Cactinomycin
Cyclophosphamide
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Protein Synthesis Inhibitors