Evolutionary Therapy for Rhabdomyosarcoma

NCT04388839 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-20339
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 18

Brief Summary

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.

Conditions

Rhabdomyosarcoma

Keywords

Soft Tissue Cancer; Skeletal Muscle Tissue Cancer; Sarcoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Overall Survival

  5 years

• Treatment-related adverse events of a certain grade or higher

  Baseline to 5 years

Study Arms (4)

Arm A - First Strike

EXPERIMENTAL

Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide

Drug: Cyclophosphamide; Drug: Vinorelbine; Drug: Actinomycin D

Arm B - Second Strike - Maintenance

EXPERIMENTAL

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: Vincristine; Drug: Cyclophosphamide; Drug: Vinorelbine; Drug: Actinomycin D; Drug: Cyclophosphamide Pill

Arm C - Adaptive Therapy

EXPERIMENTAL

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: Vincristine; Drug: Cyclophosphamide; Drug: Actinomycin D

Arm - D Conventional Therapy

ACTIVE COMPARATOR

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: Vincristine; Drug: Cyclophosphamide; Drug: Actinomycin D

Interventions

Vincristine DRUG

IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg

Arm - D Conventional Therapy; Arm B - Second Strike - Maintenance; Arm C - Adaptive Therapy

Cyclophosphamide DRUG

IV over 60 minutes with dosing ranging from 220mg to 1200mg

Arm - D Conventional Therapy; Arm A - First Strike; Arm B - Second Strike - Maintenance; Arm C - Adaptive Therapy

Vinorelbine DRUG

IV push over 6-10 minutes with dosing ranging from 4mg-25mg

Also known as: Navelbine

Arm A - First Strike; Arm B - Second Strike - Maintenance

Actinomycin D DRUG

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

Also known as: Cosmegen

Arm - D Conventional Therapy; Arm A - First Strike; Arm B - Second Strike - Maintenance; Arm C - Adaptive Therapy

Cyclophosphamide Pill DRUG

Based on Body Surface Area (BSA) round to nearest 25mg

Arm B - Second Strike - Maintenance

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Pediatric Cancer Foundation: collaborator

Study Sites (18)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Montefiore Medical Cancer Center

The Bronx, New York, 10467, United States

Location

University of North Carolina Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center, Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke Children's Hospital

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Primary Children's Medical Center/Utah

Salt Lake City, Utah, 84113, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials Website

MeSH Terms

Conditions

Rhabdomyosarcoma; Sarcoma

Interventions

Vincristine; Cyclophosphamide; Vinorelbine; Dactinomycin

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Heterocyclic Compounds, 3-Ring; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jonathan Metts, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: May 14, 2020
• Study Start: December 29, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

US (18)