NCT04994132|Active Not RecruitingPhase 3FDA Drug

A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma

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)

Children's Oncology Group ClinicalTrials.gov

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3 other identifiers

ARST2031NCI-2021-06711U10CA180886

Study Type

interventional

Target

118

Locations

5 countries

Sites

250

Timeline

RegisteredAug 2021

StartedSep 2021

CompletionJun 2026

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 Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

118

participants targeted

Target at P25-P50 for phase_3

Timeline

1mo left

Started Sep 2021

Longer than P75 for phase_3

Geographic Reach

5 countries

250 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

4.8 years study duration

Study Progress97%

Sep 2021Jun 2026

First Submitted

Initial submission to the registry

July 9, 2021

Completed

28 days until next milestone

First Posted

Study publicly available on registry

August 6, 2021

Completed

1 month until next milestone

Study Start

First participant enrolled

September 14, 2021

Completed

4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2026

Last Updated

May 5, 2026

Status Verified

February 1, 2026

Enrollment Period

4.8 years

First QC Date

July 9, 2021

Last Update Submit

May 1, 2026

Conditions

Botryoid-Type Embryonal Rhabdomyosarcoma Alveolar Rhabdomyosarcoma Embryonal Rhabdomyosarcoma Metastatic Embryonal Rhabdomyosarcoma Metastatic Rhabdomyosarcoma Solid Alveolar Rhabdomyosarcoma Spindle Cell Rhabdomyosarcoma Spindle Cell/Sclerosing Rhabdomyosarcoma

Outcome Measures

Primary Outcomes (1)

Event-free survival (EFS)
Will be estimated using the Kaplan-Meier method and will be compared between the two regimens using a log-rank test.
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 Outcomes (6)

Overall survival
Time from randomization to death of any cause, assessed up to 5 years from study enrollment
Radiologic response rate
At week 12 after study enrollment
Incidence of adverse events
Up to 5 years from study enrollment
Feasibility and safety assessed by the adverse events, toxicities and treatment delays
From study enrollment to completion of the initial 12 weeks of therapy
Association between circulating tumor-derived deoxyribonucleic acid (ctDNA) and EFS
Up to 5 years from study enrollment
+1 more secondary outcomes

Study Arms (2)

Arm A (VAC, VINO-CPO)

EXPERIMENTAL

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.

Procedure: Biospecimen CollectionProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyProcedure: Bone ScanProcedure: Computed TomographyDrug: CyclophosphamideBiological: DactinomycinProcedure: Magnetic Resonance ImagingProcedure: Positron Emission TomographyRadiation: Radiation TherapyDrug: Vincristine SulfateDrug: Vinorelbine TartrateProcedure: X-Ray Imaging

Arm B (vinorelbine, VAC, VINO-CPO)

EXPERIMENTAL

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.