Clinical Trial 20339

• Overview

  Study Title:

  Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma

  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.

  Objective:

  Primary Objectives 1. To evaluate 4 different therapeutic approaches towards improving the 3 year EFS from its current 6% to 35% in metastatic, fusion-positive rhabdomyosarcoma patients. Secondary Objectives 1. To describe the overall survival for patients treated on all 4 therapeutic approaches. 2. To describe the grade 3+ toxicities of the various approaches 3. To build, improve, and then test mathematical models for predicting and tracking responses to therapies towards improved strategies for preventing resistance and identifying potentially better strategies for utilizing different doses, schedules or agents in the management of FPRMS. 4. To evaluate physician and patient preferences for novel approaches to high risk cancer by accrual to conventional, more and less intensive systemic chemotherapy approaches in metastatic FPRMS. 5. To suggest additional biomarkers by quantifying circulating tumor DNA (ptDNA) in patients and determine if ptDNA changes over time in a manner that reflects tumor burden, presence of resistant cancer cells, response to therapy, predicts risk of progression, and informs the mathematical models. 6. To evaluate a set of radiomic biomarkers calculated from baseline and post-therapy CT and MRI scans, and compare results with treatment response and mathematical model predictions. 7. To perform single cell sequencing of circulating tumor cells to evaluate changes over time. 8. To compare the number of chemotherapy cycles delivered across all treatment arms. 9. To examine parent and patient experiences with treatment decision-making in the setting of multiple therapeutic options and a poor prognosis.

• Treatments

  Therapies:

  Chemotherapy (NOS); Radiotherapy

  Medications:

  Actinomycin D (Dactinomycin); Adriamycin (doxorubicin); Ifosfamide (); Navelbine (Vinorelbine); Radiotherapy (); Vincristine (); Vinorelbine (); cyclophosphamide (); cytoxan (cyclophosphamide); doxorubicin (); etoposide ()

• Inclusion Criteria

  • New histologic diagnosis of habdomyosarcoma
  • FISH, PCR or other molecular confirmation of PAX/FOXO1 fusion per institutional standards
  • 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: (a) ongoing or active infection not expected to resolve with current antibiotic plan (b) cardiac arrhythmia (c) 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

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