NCT05304585ClinicalTrials.gov

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

A Prospective Phase 3 Study of Patients With Newly Diagnosed Very Low-Risk and Low-Risk Fusion Negative Rhabdomyosarcoma

En recrutementAccepte des participants actuellement, selon la fiche du registre.

Contacter cette étude

En bref

Phase 3205 participants recherchés181 sites4 pays

Catégories

Oncologie100%

Enregistré dans 1 registre

ClinicalTrials.govNCT05304585Ouvrir cette fiche sur ClinicalTrials.govSynchronisé il y a 4 semaines

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How this study is set up

The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.

Present: Registered before enrolment beganFirst posted 2022-03-31; recorded start 2022-08-04
Present: Has a defined primary outcomeA primary outcome measure is listed in the record
Present: The primary outcome states a time frameThe primary outcome measure records a time frame
Not stated: Participants are not randomly assignedAllocation is recorded as non-randomised
Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
Not stated: Open label (no blinding)Masking is recorded as none (open label)
Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
Present: Sponsor has 183 other studies in this databaseCounted from the lead sponsor named in the record (Children's Oncology Group)
Present: Sponsor has posted results for at least one studyBased on the sponsor’s studies in this database

The record lists 3 conditions.
Lead sponsor type recorded as: research network.
Intervention regulatory context: investigational, within a phased regulatory pathway.

These are facts from the public registry record, not a judgement about the study. Discuss any trial with your own doctor before taking part.

What these facts mean, and what to ask · ruleset v1

Trial stature

Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.

Methodological rigourEXPLORATORY

An exploratory-stage design for a phase 3 study, judged from its ClinicalTrials.gov record.

How this score is built

Randomised allocation0/20
Non-randomised allocation
Blinding0/20
Open-label
Control arm0/15
No comparator arm stated in the record
Primary-outcome specificity10/10
Named primary outcome with a defined time frame
Endpoint type10/10
Mortality / MACE endpoint (hard clinical outcome)
Multi-centre8/8
Multi-centre: 180 sites
Data monitoring committee0/7
No data monitoring committee stated
Prospective registration5/5
Registered before the study start date
Protocol / SAP posted0/5
No protocol or SAP posted to the registry

ScaleMEDIUM

A medium-sized study, international in scope: 205 participants (target), run at 181 sites, across 4 countries.

How this score is built

Enrolment22/40
205 participants (target)
Site count25/25
180 sites
Country count7/15
4 countries
Planned duration10/10
Planned over about 96 months
Sponsor scale9/10
Children's Oncology Group has led 182 trials in our corpus

Investigator standingUNKNOWN

We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.

How this score is built

Investigator standing0/100
No investigator recorded in the registry for this trial

These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.

Résumé

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.

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.

Affections

Embryonal Rhabdomyosarcoma
Fusion-Negative Alveolar Rhabdomyosarcoma
Spindle Cell/Sclerosing Rhabdomyosarcoma

Éligibilité

Éligibilité
Sexe	Tous
Âges	Aucun minimum – 21 Years
Volontaires sains	Non

Éligibilité telle qu'elle figure dans le registre

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.

Éligibilité en énoncés simples

Les critères de cette fiche n'ont pas encore été décomposés en énoncés distincts. Le texte du registre ci-dessus est complet et fait foi.

Conception de l'étude

Conception de l'étude
Type d'étude	Interventionnelle
Phase	Phase 3
Répartition	Non randomisée
Modèle d'intervention	PARALLEL
Objectif principal	TREATMENT
Insu	NONE (0)
Recrutement	205 participants recherchés

Promoteur et collaborateurs

Children's Oncology Group Promoteur
National Cancer Institute (NCI) Collaborateurs

Groupes et interventions

Regimen M (positive mutation)EXPERIMENTAL
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.
Regimen VA (VLR RMS)EXPERIMENTAL
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.
Regimen VAC/VA (VL RMS)EXPERIMENTAL
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.

Interventions

Intervention Biopsy Procedure
Undergo tumor biopsy
Intervention Bone Scan
Undergo bone scan
Intervention Computed Tomography
Undergo CT scan
Médicament Cyclophosphamide
Given IV
Produit biologique Dactinomycin
Given IV
Intervention Magnetic Resonance Elastography
Undergo MRI
Intervention Positron Emission Tomography
Undergo PET scan
Radiothérapie Radiation Therapy
Undergo radiation
Médicament Vincristine
Given IV

Critères de jugement

Critère de jugement principal
Failure free survival (FFS) for very low risk patients
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.
Délai From study enrollment to disease progression, recurrence, or death as a first event, assessed up to 3 years
Critère de jugement principal
Failure free survival (FFS) for low risk patients
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.
Délai From study enrollment to disease progression, recurrence, or death as a first event, assessed up to 3 years
Critère de jugement secondaire
Overall survival (OS) for very low risk patients
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.
Délai From study entry to death of any cause, assessed up to 5 years
Critère de jugement secondaire
Overall survival (OS) for low risk patients
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.
Délai From study entry to death of any cause, assessed up to 5 years
Critère de jugement secondaire
Feasibility of central molecular risk stratification of patients assessed by the percentage of patients who have molecular testing results returned by 6 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.
Délai Up to 24 weeks
Autre critère de jugement
Methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma
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.
Délai Up to 5 years
Autre critère de jugement
Descriptive analysis of patients treated on Regimen M
Summary statistics will be used to provide a descriptive analysis of patients treated on Regimen M, including patient demographics, clinical characteristics and outcomes.
Délai Up to 5 years

Dates

Dates
Date de début	4 août 2022 (réelle)
Achèvement principal	30 juin 2030 (estimée)
Achèvement	30 juin 2030 (estimée)
Première publication	31 mars 2022 (réelle)
Dernière mise à jour	25 août 2026
Résultats publiés	Non précisé dans la fiche du registre
Statut vérifié pour la dernière fois	octobre 2025

Réelle signifie que l'événement a eu lieu. Estimée signifie que le promoteur s'y attend. Les deux ont un sens différent.

Lieux

178 sites sont en recrutement

Australia

Australia
Établissement	Ville	État ou région	Statut
Perth Children's Hospital	Perth	Western Australia	En recrutement
Sydney Children's Hospital	Randwick	New South Wales	En recrutement
The Children's Hospital at Westmead	Westmead	New South Wales	En recrutement

Canada

Canada
Établissement	Ville	État ou région	Statut
Alberta Children's Hospital	Calgary	Alberta	En recrutement
University of Alberta Hospital	Edmonton	Alberta	En recrutement
IWK Health Centre	Halifax	Nova Scotia	En recrutement
Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	En recrutement
The Montreal Children's Hospital of the MUHC	Montreal	Quebec	En recrutement
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)	Québec		En recrutement
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec	Suspendu
Hospital for Sick Children	Toronto	Ontario	En recrutement
British Columbia Children's Hospital	Vancouver	British Columbia	En recrutement
CancerCare Manitoba	Winnipeg	Manitoba	En recrutement

New Zealand

New Zealand
Établissement	Ville	État ou région	Statut
Christchurch Hospital	Christchurch		En recrutement
Starship Children's Hospital	Grafton	Auckland	En recrutement

United States

United States
Établissement	Ville	État ou région	Statut
Children's Hospital Medical Center of Akron	Akron	Ohio	En recrutement
Albany Medical Center	Albany	New York	En recrutement
University of New Mexico Cancer Center	Albuquerque	New Mexico	En recrutement
Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	En recrutement
C S Mott Children's Hospital	Ann Arbor	Michigan	En recrutement
Children's Healthcare of Atlanta - Arthur M Blank Hospital	Atlanta	Georgia	En recrutement
Children's Hospital Colorado	Aurora	Colorado	En recrutement
Dell Children's Medical Center of Central Texas	Austin	Texas	En recrutement
Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	En recrutement
Sinai Hospital of Baltimore	Baltimore	Maryland	En recrutement
University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	En recrutement
Children's Hospital of Alabama	Birmingham	Alabama	En recrutement
Saint Luke's Cancer Institute - Boise	Boise	Idaho	En recrutement
Massachusetts General Hospital Cancer Center	Boston	Massachusetts	En recrutement
Dana-Farber Cancer Institute	Boston	Massachusetts	En recrutement
Roswell Park Cancer Institute	Buffalo	New York	En recrutement
UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	En recrutement
West Virginia University Charleston Division	Charleston	West Virginia	En recrutement
Medical University of South Carolina	Charleston	South Carolina	En recrutement
Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	En recrutement
Novant Health Presbyterian Medical Center	Charlotte	North Carolina	En recrutement
University of Virginia Cancer Center	Charlottesville	Virginia	En recrutement
University of Chicago Comprehensive Cancer Center	Chicago	Illinois	En recrutement
University of Illinois	Chicago	Illinois	Suspendu
Lurie Children's Hospital-Chicago	Chicago	Illinois	En recrutement
Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	En recrutement
Cleveland Clinic Foundation	Cleveland	Ohio	En recrutement
Rainbow Babies and Childrens Hospital	Cleveland	Ohio	En recrutement
Prisma Health Richland Hospital	Columbia	South Carolina	En recrutement
Nationwide Children's Hospital	Columbus	Ohio	En recrutement
Driscoll Children's Hospital	Corpus Christi	Texas	En recrutement
Medical City Dallas Hospital	Dallas	Texas	En recrutement
UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	En recrutement
Geisinger Medical Center	Danville	Pennsylvania	En recrutement
Dayton Children's Hospital	Dayton	Ohio	En recrutement

131 sites supplémentaires sont indiqués dans la fiche du registre.

Documents de l'étude

Aucun document n'est lié dans cette fiche du registre.

Évolution au fil du temps

25 août 2026
Site ajouté
1 site added (181 total)
180181

Registre: ClinicalTrials.gov · NCT########

https://xmedica.io/trials/ctgov/NCT05304585