Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 12
- 试验地点
- 18
- 主要终点
- Adaptive Therapy Event Free Survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Arm A - First Strike
Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
干预措施: Cyclophosphamide (Drug)
Arm A - First Strike
Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
干预措施: Vinorelbine (Drug)
Arm A - First Strike
Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
干预措施: Actinomycin D (Drug)
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
干预措施: Vincristine (Drug)
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
干预措施: Cyclophosphamide (Drug)
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
干预措施: Vinorelbine (Drug)
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
干预措施: Actinomycin D (Drug)
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
干预措施: Cyclophosphamide Pill (Drug)
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
干预措施: Vincristine (Drug)
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
干预措施: Cyclophosphamide (Drug)
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
干预措施: Actinomycin D (Drug)
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.
干预措施: Vincristine (Drug)
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.
干预措施: Cyclophosphamide (Drug)
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.
干预措施: Actinomycin D (Drug)
结局指标
主要结局
Adaptive Therapy Event Free Survival
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- Overall Survival(5 years)
- Treatment-related adverse events of a certain grade or higher(Baseline to 5 years)