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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05304585




Registration number
NCT05304585
Ethics application status
Date submitted
24/02/2022
Date registered
31/03/2022
Date last updated
4/12/2024

Titles & IDs
Public title
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Scientific title
A Prospective Phase 3 Study of Patients With Newly Diagnosed Very Low-Risk and Low-Risk Fusion Negative Rhabdomyosarcoma
Secondary ID [1] 0 0
NCI-2022-01012
Secondary ID [2] 0 0
ARST2032
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Embryonal Rhabdomyosarcoma 0 0
Fusion-Negative Alveolar Rhabdomyosarcoma 0 0
Spindle Cell/Sclerosing Rhabdomyosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biopsy
Treatment: Surgery - Bone Scan
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Cyclophosphamide
Treatment: Other - Dactinomycin
Treatment: Surgery - Magnetic Resonance Elastography
Treatment: Surgery - Positron Emission Tomography
Treatment: Other - Radiation Therapy
Treatment: Drugs - Vincristine

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.

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.

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.


Treatment: Surgery: Biopsy
Undergo tumor biopsy

Treatment: Surgery: Bone Scan
Undergo bone scan

Treatment: Surgery: Computed Tomography
Undergo CT scan

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Other: Dactinomycin
Given IV

Treatment: Surgery: Magnetic Resonance Elastography
Undergo MRI

Treatment: Surgery: Positron Emission Tomography
Undergo PET scan

Treatment: Other: Radiation Therapy
Undergo radiation

Treatment: Drugs: Vincristine
Given IV
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Failure free survival (FFS) for very low risk patients
Timepoint [1] 0 0
From study enrollment to disease progression, recurrence, or death as a first event, assessed up to 3 years
Primary outcome [2] 0 0
Failure free survival (FFS) for low risk patients
Timepoint [2] 0 0
From study enrollment to disease progression, recurrence, or death as a first event, assessed up to 3 years
Secondary outcome [1] 0 0
Overall survival (OS) for very low risk patients
Timepoint [1] 0 0
From study entry to death of any cause, assessed up to 5 years
Secondary outcome [2] 0 0
Overall survival (OS) for low risk patients
Timepoint [2] 0 0
From study entry to death of any cause, assessed up to 5 years
Secondary outcome [3] 0 0
Feasibility of central molecular risk stratification of patients assessed by the percentage of patients who have molecular testing results returned by 6 weeks
Timepoint [3] 0 0
Up to 24 weeks

Eligibility
Key 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.
Minimum age
No limit
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2030
Actual
Sample size
Target
205
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Idaho
Country [13] 0 0
United States of America
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Illinois
Country [14] 0 0
United States of America
State/province [14] 0 0
Indiana
Country [15] 0 0
United States of America
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Iowa
Country [16] 0 0
United States of America
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Kentucky
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United States of America
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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United States of America
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Missouri
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United States of America
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Nebraska
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United States of America
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Nevada
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United States of America
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New Hampshire
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United States of America
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New Jersey
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United States of America
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New York
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United States of America
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North Carolina
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North Dakota
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Ohio
Country [33] 0 0
United States of America
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Oklahoma
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Oregon
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United States of America
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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United States of America
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
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Canada
State/province [46] 0 0
Alberta
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Canada
State/province [47] 0 0
Manitoba
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Canada
State/province [48] 0 0
Nova Scotia
Country [49] 0 0
Canada
State/province [49] 0 0
Quebec
Country [50] 0 0
New Zealand
State/province [50] 0 0
Auckland
Country [51] 0 0
New Zealand
State/province [51] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Josephine H Haduong
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05304585