Clinical Trials /

Evolutionary Therapy for Rhabdomyosarcoma

NCT04388839

Description:

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.

Related Conditions:
  • Rhabdomyosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evolutionary Therapy for Rhabdomyosarcoma
  • Official Title: Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma

Clinical Trial IDs

  • ORG STUDY ID: MCC-20339
  • NCT ID: NCT04388839

Conditions

  • Rhabdomyosarcoma

Interventions

DrugSynonymsArms
VincristineArm - D Conventional Therapy
CyclophosphamideArm - D Conventional Therapy
VinorelbineNavelbineArm A - First Strike
Actinomycin DCosmegenArm - D Conventional Therapy
Cyclophosphamide PillArm B - Second Strike - Maintenance

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A - First StrikeExperimentalParticipants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
  • Cyclophosphamide
  • Vinorelbine
  • Actinomycin D
Arm B - Second Strike - MaintenanceExperimentalParticipants 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
  • Vincristine
  • Cyclophosphamide
  • Vinorelbine
  • Actinomycin D
  • Cyclophosphamide Pill
Arm C - Adaptive TherapyExperimentalTherapy with VAC that starts and stops based on response, adaptive timing of therapy, with a prolonged time to progression rather than complete remission goal
  • Vincristine
  • Cyclophosphamide
  • Actinomycin D
Arm - D Conventional TherapyActive ComparatorParticipants 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.
  • Vincristine
  • Cyclophosphamide
  • Actinomycin D

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 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.

          -  Pregnancy or Breast Feeding: Pregnant or breast-feeding women will not be entered on
             this study, 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.

          -  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.

          -  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 would be 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

          -  Participants who are considered unable to comply with the safety monitoring
             requirements of the study are not eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:First Strike Event Free Survival
Time Frame:Baseline to 3 years
Safety Issue:
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.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:5 years
Safety Issue:
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
Measure:Treatment-related adverse events of a certain grade or higher
Time Frame:Baseline to 5 years
Safety Issue:
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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Soft Tissue Cancer
  • Skeletal Muscle Tissue Cancer
  • Sarcoma

Last Updated

September 3, 2020