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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04994132




Registration number
NCT04994132
Ethics application status
Date submitted
9/07/2021
Date registered
6/08/2021
Date last updated
20/12/2024

Titles & IDs
Public title
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
Scientific title
A Randomized Phase 3 Trial of Vinorelbine, Dactinomycin, and Cyclophosphamide (VINO-AC) Plus Maintenance Chemotherapy With Vinorelbine and Oral Cyclophosphamide (VINO-CPO) vs Vincristine, Dactinomycin and Cyclophosphamide (VAC) Plus VINO-CPO Maintenance in Patients With High Risk Rhabdomyosarcoma (HR-RMS)
Secondary ID [1] 0 0
NCI-2021-06711
Secondary ID [2] 0 0
ARST2031
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alveolar Rhabdomyosarcoma 0 0
Botryoid-Type Embryonal Rhabdomyosarcoma 0 0
Embryonal Rhabdomyosarcoma 0 0
Metastatic Embryonal Rhabdomyosarcoma 0 0
Metastatic Rhabdomyosarcoma 0 0
Solid Alveolar Rhabdomyosarcoma 0 0
Spindle Cell 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 - Biospecimen Collection
Treatment: Surgery - Bone Marrow Aspiration
Treatment: Surgery - Bone Marrow Biopsy
Treatment: Surgery - Bone Scan
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Cyclophosphamide
Treatment: Other - Dactinomycin
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Surgery - Positron Emission Tomography
Treatment: Other - Radiation Therapy
Treatment: Drugs - Vincristine Sulfate
Treatment: Drugs - Vinorelbine Tartrate
Treatment: Surgery - X-Ray Imaging

Experimental: Arm A (VAC, VINO-CPO) - Patients receive vincristine sulfate IV on days 1, 8 and 15 of cycles 1-4, 7, 8, 11, and 12, and day 1 of cycles 5, 6, 9, 10, 13, and 14. Patients also receive dactinomycin IV over 1-15 minutes or IVP over 1-5 minutes on day 1 of cycles 1-5, 8-10, and 11-14, and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on weeks 13 and 40.

MAINTENANCE: Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15, and cyclophosphamide PO on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients in both arms undergo CT, MRI, PET, x-ray imaging, and/or bone scan, as well as blood sample collection throughout the trial. Patients may also undergo bone marrow aspiration and/or biopsy as clinically indicated.

Experimental: Arm B (vinorelbine, VAC, VINO-CPO) - Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8, vincristine sulfate IV on day 15, dactinomycin IV over 1-15 minutes or IVP over 1-5 minutes on day 1 of cycles 1-5 and 8-14, and cyclophosphamide IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on weeks 13 and 40.

MAINTENANCE: Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15, and cyclophosphamide PO on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients in both arms undergo CT, MRI, PET, x-ray imaging, and/or bone scan, as well as blood sample collection throughout the trial. Patients may also undergo bone marrow aspiration and/or biopsy as clinically indicated.


Treatment: Surgery: Biospecimen Collection
Undergo blood sample collection

Treatment: Surgery: Bone Marrow Aspiration
Undergo bone marrow aspiration

Treatment: Surgery: Bone Marrow Biopsy
Undergo bone marrow biopsy

Treatment: Surgery: Bone Scan
Undergo bone scan

Treatment: Surgery: Computed Tomography
Undergo CT

Treatment: Drugs: Cyclophosphamide
Given IV or PO

Treatment: Other: Dactinomycin
Given IV

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Surgery: Positron Emission Tomography
Undergo PET

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Drugs: Vincristine Sulfate
Given IV

Treatment: Drugs: Vinorelbine Tartrate
Given IV

Treatment: Surgery: X-Ray Imaging
Undergo x-ray imaging
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
Event-free survival
Timepoint [1] 0 0
Time from randomization to an event defined as disease relapse/progression, second malignancy, or death, whichever occurs first, assessed up to 5 years from study enrollment
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
Time from randomization to death of any cause, assessed up to 5 years from study enrollment
Secondary outcome [2] 0 0
Radiologic response rate
Timepoint [2] 0 0
At week 12 after study enrollment
Secondary outcome [3] 0 0
Incidence of adverse events
Timepoint [3] 0 0
Up to 5 years from study enrollment
Secondary outcome [4] 0 0
Feasibility and safety assessed by the adverse events, toxicities and treatment delays
Timepoint [4] 0 0
From study enrollment to completion of the initial 12 weeks of therapy

Eligibility
Key inclusion criteria
* Patients must be =< 50 years of age at the time of enrollment
* Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification are eligible to enroll on the study based upon stage, group, and age, as below. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (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). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants

* ERMS

* Stage 4, group IV, >= 10 years of age
* ARMS

* Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age
* Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):

* Age; Maximum serum creatinine (mg/dL)
* 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
* 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
* 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
* 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
* 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
* 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
* 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
* >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
* Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)

* If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x ULN for age
* 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
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with evidence of uncontrolled infection are not eligible
* RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed
* Patients with central nervous system involvement of RMS as defined below:

* Malignant cells detected in cerebrospinal fluid
* Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed).
* Diffuse leptomeningeal disease
* Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment.

* Note: the following exception:

* Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation
* Note: Patients who have received or are receiving 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 and vinorelbine are sensitive substrates of 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
* 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
Randomised controlled 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
118
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [5] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 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
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
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Arkansas
Country [5] 0 0
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State/province [5] 0 0
California
Country [6] 0 0
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Colorado
Country [7] 0 0
United States of America
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Connecticut
Country [8] 0 0
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Delaware
Country [9] 0 0
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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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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Mississippi
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Missouri
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Nebraska
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Nevada
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New Jersey
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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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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Tennessee
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Texas
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Utah
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Vermont
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West Virginia
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Wisconsin
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Alberta
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Manitoba
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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Puerto Rico
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Caguas
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Saudi Arabia
State/province [54] 0 0
Riyadh

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
Wendy Allen-Rhoades
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/NCT04994132