Evolutionary Therapy for Rhabdomyosarcoma

Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma

This clinical trial will evaluate 4 different strategies of chemotherapy schedules in newly diagnosed participants with metastatic Fusion Positive (alveolar) Rhabdomyosarcoma. The participant and their physician will choose from: Arm A) a first strike therapy, Arm B) a first strike-second strike (maintenance) therapy, Arm C) an adaptively timed therapy, and Arm D) conventional chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Rhabdomyosarcoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Vinorelbine; Drug: Actinomycin D; Drug: Vincristine; Drug: Cyclophosphamide Pill

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital of Colorado
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami - Sylvester Comprehensive Cancer Center
    • St. Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Medical Center, Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke Children's Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt - Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Medical Center/Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have a new histologic diagnosis of rhabdomyosarcoma
• Participants must have FISH, PCR or other molecular confirmation of PAX/FOXO1 fusion per institutional standards
• Participants must have sufficient tissue (up to 10 unstained FFPE) for correlative testing
• All participants must have distant metastatic disease; either biopsy positive or PET avid extranodal or distant nodal lesions determined by the investigator to be metastatic disease. Patients with a single distant metastatic site that has been excised prior to study entry are eligible
• No prior systemic chemotherapy
• Participants enrolled to Arm B, maintenance, must be able to take oral cyclophosphamide. Note: enteral administration of cyclophosphamide is allowable.
• Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception during and after treatment or abstinence.
• Women of childbearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
• Men who are sexually active with women of child bearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
• All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.

Exclusion Criteria:

• Participants with regional lymph nodes as the only site of disease are not eligible. Distant nodal sites alone are eligible
• Participants who are receiving any other investigational agents for rhabdomyosarcoma are ineligible
• Participants must not be receiving any additional medicines being given for the specific purpose of treating cancer. Alternative medications including, but not limited to cannabis based products would not be a reason for exclusion

• Participants are ineligible if they have uncontrolled intercurrent illness including, but not limited to:

  • ongoing or active infection not expected to resolve with current antibiotic plan
  • cardiac arrhythmia
  • psychiatric illness/social situations that would limit compliance with study requirements
• Patients who are pregnant or breastfeeding are not eligible because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of starting protocol therapy.
• Participants who are considered unable to comply with the safety monitoring requirements of the study are not eligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - First Strike; Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide	Drug: Cyclophosphamide; IV over 60 minutes with dosing ranging from 220mg to 1200mg; Drug: Vinorelbine; IV push over 6-10 minutes with dosing ranging from 4mg-25mg; Other Names: Navelbine; Drug: Actinomycin D; Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg; Other Names: Cosmegen
Experimental: Arm B - Second Strike - Maintenance; Participants will receive conventional doses of Vincristine/Actinomycin D/Cyclophosphamide (VAC) until complete response (CR) for 12-42 weeks and then switch to up to 2 years of vinorelbine/oral cyclophoshamide	Drug: Cyclophosphamide; IV over 60 minutes with dosing ranging from 220mg to 1200mg; Drug: Vinorelbine; IV push over 6-10 minutes with dosing ranging from 4mg-25mg; Other Names: Navelbine; Drug: Actinomycin D; Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg; Other Names: Cosmegen; Drug: Vincristine; IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg; Drug: Cyclophosphamide Pill; Based on Body Surface Area (BSA) round to nearest 25mg
Experimental: Arm C - Adaptive Therapy; Therapy with VAC that starts and stops based on response, adaptive timing of therapy, with a prolonged time to progression rather than complete remission goal	Drug: Cyclophosphamide; IV over 60 minutes with dosing ranging from 220mg to 1200mg; Drug: Actinomycin D; Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg; Other Names: Cosmegen; Drug: Vincristine; IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg
Active Comparator: Arm - D Conventional Therapy; Participants will receive a chemotherapy combination based on published trials. An example would be 42 weeks of VAC but may also include irinotecan, doxorubicin, ifosfamide, etoposide.	Drug: Cyclophosphamide; IV over 60 minutes with dosing ranging from 220mg to 1200mg; Drug: Actinomycin D; Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg; Other Names: Cosmegen; Drug: Vincristine; IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First Strike Event Free Survival	Participants who choose the first strike treatment will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) any recurrence (local or regional, or distant) and (2) death due to any cause.	Baseline to 3 years
Second Strike Event Free Survival	Participants who choose the second strike treatment will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) any recurrence (local or regional, or distant) and (2) death due to any cause	Baseline to 3 years
Adaptive Therapy Event Free Survival	Participants who choose the adaptive therapy will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) progression that does not respond to additional VAC dosing and (2) death due to any cause	Baseline to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time to event endpoint of overall survival is defined as the duration of time from diagnosis to death or last follow-up, where event would be death from any cause	5 years
Treatment-related adverse events of a certain grade or higher	Number of participants with treatment-related adverse events of a certain grade or higher and hematological/biochemical toxicities based on laboratory measurements as assessed by CTCAE v5.0	Baseline to 5 years

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Pediatric Cancer Foundation
• Investigators: Principal Investigator: Jonathan Metts, MD, Moffitt Cancer Center

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 14, 2020

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Sarcoma; Soft Tissue Cancer; Skeletal Muscle Tissue Cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue; Myosarcoma; Sarcoma; Rhabdomyosarcoma; Peptides; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Alkaloids; Polycyclic Compounds; Indoles; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Macrocyclic Compounds; Peptides, Cyclic; Heterocyclic Compounds, 3-Ring; Vinorelbine; Cyclophosphamide; Vincristine; Dactinomycin
• Other Study ID Numbers: MCC-20339

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes