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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04994132




Registration number
NCT04994132
Ethics application status
Date submitted
9/07/2021
Date registered
6/08/2021
Date last updated
22/04/2024

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
Other interventions - 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

Other interventions: 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
Other interventions
Intervention code [4] 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
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
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [4] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment postcode(s) [4] 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
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Arizona
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United States of America
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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United States of America
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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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Minnesota
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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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Utah
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Vermont
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West Virginia
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Wisconsin
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Canada
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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
This phase III trial compares the safety and effect of adding vinorelbine to vincristine,
dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk
rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after
treatment or spread to other parts of the body. This study will also examine if adding
maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the
cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in
a class of medications called vinca alkaloids. They work by stopping cancer cells from
growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only
used in cancer chemotherapy. It works by damaging the cell's deoxyribonucleic acid (DNA) and
may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating
agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the
body's immune response. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are
chemotherapy medications that work in different ways to stop the growth of cancer cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. This trial may have the potential to eliminate rhabdomyosarcoma for a long time or
for the rest of patient's life.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04994132
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04994132