Clinical trial NCT04388839: Evolutionary Therapy for Rhabdomyosarcoma
Official title: Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rhabdomyosarcoma
Keywords: Soft Tissue Cancer
Skeletal Muscle Tissue Cancer
Sarcoma
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: National Pediatric Cancer Foundation
First posted: 2020-05-14
Enrollment: 28
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: First Strike Event Free Survival
timeFrame: Baseline to 3 years
measure: Second Strike Event Free Survival
timeFrame: Baseline to 3 years
measure: Adaptive Therapy Event Free Survival
timeFrame: Baseline to 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 5 years
measure: Treatment-related adverse events of a certain grade or higher
timeFrame: Baseline to 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Bronx
country: United States
facility: Montefiore Medical Cancer Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center, Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke Children's Hospital
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center/Utah
state: Utah
Study officials:
affiliation: Moffitt Cancer Center
name: Jonathan Metts, MD
role: PRINCIPAL_INVESTIGATOR
References: