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Purpose

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.

Condition

Eligibility

Eligible Ages
All ages
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: Vincristine
    IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg
  • 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: 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: Vincristine
    IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg
  • 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
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: Vincristine
    IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg
  • 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

Recruiting Locations

University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama 35294
Contact:
Jennifer Madison
205-638-2975
jennifermadison@uabmc.edu

More Details

Status
Recruiting
Sponsor
H. Lee Moffitt Cancer Center and Research Institute

Study Contact

Jessica Crimella, BSN, RN
813-745-6250
Jessica.Crimella@moffitt.org

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.