Evolutionary Therapy for Rhabdomyosarcoma
- Conditions
- Rhabdomyosarcoma
- Interventions
- Registration Number
- NCT04388839
- 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 available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 28
- 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.
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Participants with regional lymph nodes as the only site of disease are not eligible. Distant nodal sites alone are eligible
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Participants who are receiving any other investigational agents for rhabdomyosarcoma are ineligible
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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
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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
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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.
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Participants who are considered unable to comply with the safety monitoring requirements of the study are not eligible
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B - Second Strike - Maintenance Cyclophosphamide Pill 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 B - Second Strike - Maintenance Vinorelbine 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 B - Second Strike - Maintenance Actinomycin D 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 - D Conventional Therapy Vincristine 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. Arm A - First Strike Cyclophosphamide Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide Arm A - First Strike Actinomycin D Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide Arm A - First Strike Vinorelbine Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide Arm B - Second Strike - Maintenance Vincristine 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 B - Second Strike - Maintenance 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 Arm C - Adaptive Therapy Vincristine 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 C - Adaptive Therapy Cyclophosphamide 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 C - Adaptive Therapy Actinomycin D 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 - D Conventional Therapy Cyclophosphamide 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. Arm - D Conventional Therapy Actinomycin D 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.
- Primary Outcome Measures
Name Time Method Adaptive Therapy Event Free Survival 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
First Strike Event Free Survival 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 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
- Secondary Outcome Measures
Name Time Method Overall Survival 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 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
Trial Locations
- Locations (18)
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Primary Children's Medical Center/Utah
🇺🇸Salt Lake City, Utah, United States
University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Children's Hospital of Colorado
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
University of Miami - Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Duke Children's Hospital
🇺🇸Durham, North Carolina, United States
Carolinas Medical Center, Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Vanderbilt - Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
MD Anderson
🇺🇸Houston, Texas, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Florida
🇺🇸Gainesville, Florida, United States
University of North Carolina Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Montefiore Medical Cancer Center
🇺🇸Bronx, New York, United States