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Evolutionary Therapy for Rhabdomyosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04388839
Recruitment Status : Recruiting
First Posted : May 14, 2020
Last Update Posted : September 7, 2020
Sponsor:
Collaborator:
National Pediatric Cancer Foundation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE May 11, 2020
First Posted Date  ICMJE May 14, 2020
Last Update Posted Date September 7, 2020
Actual Study Start Date  ICMJE September 3, 2020
Estimated Primary Completion Date December 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2020)
  • First Strike Event Free Survival [ Time Frame: Baseline to 3 years ]
    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.
  • Second Strike Event Free Survival [ Time Frame: Baseline to 3 years ]
    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
  • Adaptive Therapy Event Free Survival [ Time Frame: Baseline to 3 years ]
    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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2020)
  • Overall Survival [ Time Frame: 5 years ]
    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
  • Treatment-related adverse events of a certain grade or higher [ Time Frame: Baseline to 5 years ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evolutionary Therapy for Rhabdomyosarcoma
Official Title  ICMJE Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rhabdomyosarcoma
Intervention  ICMJE
  • 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 Name: 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 Name: Cosmegen
  • Drug: Cyclophosphamide Pill
    Based on Body Surface Area (BSA) round to nearest 25mg
Study Arms  ICMJE
  • Experimental: Arm A - First Strike
    Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Vinorelbine
    • Drug: Actinomycin D
  • 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
    Interventions:
    • Drug: Vincristine
    • Drug: Cyclophosphamide
    • Drug: Vinorelbine
    • Drug: Actinomycin D
    • Drug: Cyclophosphamide Pill
  • 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
    Interventions:
    • Drug: Vincristine
    • Drug: Cyclophosphamide
    • Drug: Actinomycin D
  • 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.
    Interventions:
    • Drug: Vincristine
    • Drug: Cyclophosphamide
    • Drug: Actinomycin D
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 11, 2020)
28
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2027
Estimated Primary Completion Date December 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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.
  • Pregnancy or Breast Feeding: Pregnant or breast-feeding women will not be entered on this study, 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.
  • 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.
  • 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 would be 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
  • Participants who are considered unable to comply with the safety monitoring requirements of the study are not eligible
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jessica Crimella, BSN, RN 813-745-6250 Jessica.Crimella@moffitt.org
Contact: Stella Valavanis, MPH 813-745-6986 Stella.Valavanis@moffitt.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04388839
Other Study ID Numbers  ICMJE MCC-20339
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE National Pediatric Cancer Foundation
Investigators  ICMJE
Principal Investigator: Damon Reed, MD Moffitt Cancer Center
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP