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.
Brief Title
Evolutionary Therapy for Rhabdomyosarcoma
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
813-745-6250
Central Contact Email
Jessica.Crimella@moffitt.org
Central Contact Role
Contact
Central Contact Phone
813-745-6986
Central Contact Email
Stella.Valavanis@moffitt.org
Completion Date
Completion Date Type
Estimated
Conditions
Rhabdomyosarcoma
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
* 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
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
Soft Tissue Cancer
Skeletal Muscle Tissue Cancer
Sarcoma
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
NCT Id
NCT04388839
Org Class
Other
Org Full Name
H. Lee Moffitt Cancer Center and Research Institute
Org Study Id
MCC-20339
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma
Primary Outcomes
Outcome 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.
Outcome Measure
First Strike Event Free Survival
Outcome Time Frame
Baseline to 3 years
Outcome 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
Outcome Measure
Second Strike Event Free Survival
Outcome Time Frame
Baseline to 3 years
Outcome 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
Outcome Measure
Adaptive Therapy Event Free Survival
Outcome Time Frame
Baseline to 3 years
Secondary Outcomes
Outcome 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
Outcome Time Frame
5 years
Outcome Measure
Overall Survival
Outcome 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
Outcome Time Frame
Baseline to 5 years
Outcome Measure
Treatment-related adverse events of a certain grade or higher
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Alice Lee
Investigator Email
alee5@montefiore.org