Evolutionary Inspired Therapy for the Treatment of Fusion Positive Newly Diagnosed, Metastatic Rhabdomyosarcoma
Evolutionary Inspired Therapy for the Treatment of Fusion Positive Newly Diagnosed, Metastatic Rhabdomyosarcoma
This phase II trial investigates evolutionary inspired therapy in treating fusion positive rhabdomyosarcoma that is newly diagnosed and has spread to other places in the body (metastatic). Chemotherapy drugs, such as vinorelbine, vincristine sulfate, and actinomycin D, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cyclophosphamide is used to decrease the body's immune response and may inhibit DNA replication and initiate cell death. This study is being done to determine which of 4 different therapeutic treatments will have the best chance of the disease not worsening or coming back.
Pediatrics,
Sarcoma
Phase II
Both
Chemotherapy - cytotoxic
Cyclophosphamide,
Dactinomycin (actinomycin-D),
Doxorubicin,
Etoposide,
Ifosfamide,
Irinotecan,
Vincristine,
Vinorelbine
Borinstein, Scott
National
Vanderbilt University
09-03-2021
Eligibility
0 Years
BOTH
NO
Inclusion Criteria:
Patients must have a new histologic diagnosis of rhabdomyosarcoma
Patients must have fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) or other molecular confirmation of PAX/FOXO1 fusion per institutional standards NOTE: Patients with pending fusion status at the time of enrollment are eligible to start therapy on any arm of the trial.
Patients must have sufficient tissue (up to 10 unstained formalin-fixed paraffin-embedded [FFPE]) for correlative testing
All patients must have distant metastatic disease; either biopsy positive or positron emission tomography (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
Patients 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:
Patients with regional lymph nodes as the only site of disease are not eligible. Distant nodal sites alone are eligible
Patients who are receiving any other investigational agents for rhabdomyosarcoma are ineligible
Patients 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
Patients 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 considered unable to comply with the safety monitoring requirements of the study are not eligible
Patients who are pregnant or breastfeeding are not eligible because there is no available information regarding human fetal or teratogenic toxicities. Females of [TKE1] childbearing potential must have a negative serum or urine pregnancy test within 24 hours of starting protocol therapy
Patients must have a new histologic diagnosis of rhabdomyosarcoma
Patients must have fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) or other molecular confirmation of PAX/FOXO1 fusion per institutional standards NOTE: Patients with pending fusion status at the time of enrollment are eligible to start therapy on any arm of the trial.
Patients must have sufficient tissue (up to 10 unstained formalin-fixed paraffin-embedded [FFPE]) for correlative testing
All patients must have distant metastatic disease; either biopsy positive or positron emission tomography (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
Patients 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:
Patients with regional lymph nodes as the only site of disease are not eligible. Distant nodal sites alone are eligible
Patients who are receiving any other investigational agents for rhabdomyosarcoma are ineligible
Patients 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
Patients 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 considered unable to comply with the safety monitoring requirements of the study are not eligible
Patients who are pregnant or breastfeeding are not eligible because there is no available information regarding human fetal or teratogenic toxicities. Females of [TKE1] childbearing potential must have a negative serum or urine pregnancy test within 24 hours of starting protocol therapy
