Back to resultsEvolutionary Therapy for Rhabdomyosarcoma
Primary Purpose
Rhabdomyosarcoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vincristine
Cyclophosphamide
Vinorelbine
Actinomycin D
Cyclophosphamide Pill
Sponsored by
About this trial
This is an interventional treatment trial for Rhabdomyosarcoma focused on measuring Soft Tissue Cancer, Skeletal Muscle Tissue Cancer, Sarcoma
Eligibility Criteria
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
Sites / Locations
- University of Alabama at Birmingham Comprehensive Cancer CenterRecruiting
- Children's Hospital of ColoradoRecruiting
- Connecticut Children's Medical CenterRecruiting
- University of FloridaRecruiting
- University of Miami - Sylvester Comprehensive Cancer CenterRecruiting
- Johns Hopkins All Children's HospitalRecruiting
- Moffitt Cancer CenterRecruiting
- Montefiore Medical Cancer CenterRecruiting
- Roswell Park Comprehensive Cancer CenterRecruiting
- University of North Carolina Lineberger Comprehensive Cancer CenterRecruiting
- Carolinas Medical Center, Levine Cancer InstituteRecruiting
- Duke Children's HospitalRecruiting
- Cleveland ClinicRecruiting
- Nationwide Children's HospitalRecruiting
- Vanderbilt - Ingram Cancer CenterRecruiting
- University of Texas Southwestern Medical CenterRecruiting
- MD AndersonRecruiting
- Primary Children's Medical Center/UtahRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
Arm A - First Strike
Arm B - Second Strike - Maintenance
Arm C - Adaptive Therapy
Arm - D Conventional Therapy
Arm Description
Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
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
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
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.
Outcomes
Primary Outcome Measures
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.
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
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
Secondary Outcome Measures
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
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
Full Information
NCT ID
NCT04388839
First Posted
May 11, 2020
Last Updated
October 17, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Pediatric Cancer Foundation
1. Study Identification
Unique Protocol Identification Number
NCT04388839
Brief Title
Evolutionary Therapy for Rhabdomyosarcoma
Official Title
Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 27, 2020 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Pediatric Cancer Foundation
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rhabdomyosarcoma
Keywords
Soft Tissue Cancer, Skeletal Muscle Tissue Cancer, Sarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A - First Strike
Arm Type
Experimental
Arm Description
Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
Arm Title
Arm B - Second Strike - Maintenance
Arm Type
Experimental
Arm Description
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
Arm Title
Arm C - Adaptive Therapy
Arm Type
Experimental
Arm Description
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
Arm Title
Arm - D Conventional Therapy
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
IV over 60 minutes with dosing ranging from 220mg to 1200mg
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Other Intervention Name(s)
Navelbine
Intervention Description
IV push over 6-10 minutes with dosing ranging from 4mg-25mg
Intervention Type
Drug
Intervention Name(s)
Actinomycin D
Other Intervention Name(s)
Cosmegen
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide Pill
Intervention Description
Based on Body Surface Area (BSA) round to nearest 25mg
Primary Outcome Measure Information:
Title
First Strike Event Free Survival
Description
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.
Time Frame
Baseline to 3 years
Title
Second Strike Event Free Survival
Description
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
Time Frame
Baseline to 3 years
Title
Adaptive Therapy Event Free Survival
Description
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
Time Frame
Baseline to 3 years
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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
Time Frame
5 years
Title
Treatment-related adverse events of a certain grade or higher
Description
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
Time Frame
Baseline to 5 years
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jessica Crimella, BSN, RN
Phone
813-745-6250
Email
Jessica.Crimella@moffitt.org
First Name & Middle Initial & Last Name or Official Title & Degree
Stella Valavanis, MPH
Phone
813-745-6986
Email
Stella.Valavanis@moffitt.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan MEtts, MD
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Madison
Phone
205-638-2975
Email
jennifermadison@uabmc.edu
First Name & Middle Initial & Last Name & Degree
Bridget Tate
Phone
205-638-2984
Email
btate@peds.uab.edu
First Name & Middle Initial & Last Name & Degree
Elizabeth Alva, MD
Facility Name
Children's Hospital of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Miller
Phone
720-777-6484
Email
Sarah.Miller3@childrenscolorado.org
First Name & Middle Initial & Last Name & Degree
Emily Blauel-Bocko, MD
Facility Name
Connecticut Children's Medical Center
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robin Arens
Phone
860-545-9637
Email
Rarens@ConnecticutChildrens.org
First Name & Middle Initial & Last Name & Degree
Michael Scott Isakoff, MD
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley P Bayne
Phone
352-265-0111
Email
abayne@ufl.edu
First Name & Middle Initial & Last Name & Degree
Joanne P Lagmay, MD
Facility Name
University of Miami - Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Pavicic
Phone
305-585-5635
Email
EPavicic@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Aditi Dhir, MD
Facility Name
Johns Hopkins All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brittani Froug
Phone
727-767-2428
Email
BFroug1@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Emily Riffle
Phone
1 727-767-3987
Email
ERiffle2@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Jonathan Metts, MD
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica R Crimella, BSN, RN
Phone
813-745-6250
Email
Jessica.Crimella@moffitt.org
First Name & Middle Initial & Last Name & Degree
Jonathan Metts, MD
Facility Name
Montefiore Medical Cancer Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Zylber
Phone
718-741-2672
Email
RZylber@montefiore.org
First Name & Middle Initial & Last Name & Degree
Alice Lee, MD
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Guilford
Phone
716-845-4700
Email
Stephanie.Guilford@roswellpark.org
First Name & Middle Initial & Last Name & Degree
Ajay Gupta, MD
Facility Name
University of North Carolina Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juanita Cuffee
Phone
919-966-7629
Email
juanita_cuffee@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Patrick Thompson, MD
Facility Name
Carolinas Medical Center, Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Devika Srivastava
Phone
980-442-2354
Email
Devika.Srivastava@atriumhealth.org
First Name & Middle Initial & Last Name & Degree
Abigail Moore
Phone
1 980-442-2355
Email
Abigail.Moore@atriumhealth.org
First Name & Middle Initial & Last Name & Degree
Javier Oesterheld, MD
Facility Name
Duke Children's Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lars Wagner, MD
Phone
919-684-2410
Email
lars.wagner@duke.edu
First Name & Middle Initial & Last Name & Degree
Lars Wagner, MD
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Serna
Phone
216-442-5806
Email
Sernam3@ccf.org
First Name & Middle Initial & Last Name & Degree
Matteo Trucco, MD
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hannah Johns
Phone
614-722-8990
Email
Hannah.Johns@nationwidechildrens.org
First Name & Middle Initial & Last Name & Degree
Bhuvana Setty, MD
Facility Name
Vanderbilt - Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Blatner
Phone
615-875-6321
Email
Joshua.Blatner@vumc.org
First Name & Middle Initial & Last Name & Degree
Scott Borinstein, MD
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nupur Goel
Phone
214-456-1003
Email
Nupur.Goel@childrens.com
First Name & Middle Initial & Last Name & Degree
Patrick Leavey, MD
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Latasha Williams
Phone
713-563-0524
Email
ldwilliams1@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Jonathan Gill, MD
Facility Name
Primary Children's Medical Center/Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Jensen
Phone
801-662-4718
Email
Jessica.Jensen@imail.org
First Name & Middle Initial & Last Name & Degree
Michelle Grant
Phone
1 801-662-4778
Email
Michelle.Grant@imail.org
First Name & Middle Initial & Last Name & Degree
Matthew Dietz, MD
12. IPD Sharing Statement
Links:
URL
https://www.moffitt.org/clinical-trials-research/clinical-trials/
Description
Moffitt Cancer Center Clinical Trials Website
Learn more about this trial
Evolutionary Therapy for Rhabdomyosarcoma
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