Evolutionary Therapy for Rhabdomyosarcoma

Rhabdomyosarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04388839
• Other study ID #: MCC-20339
• Status: Recruiting
• Phase: Phase 2
• Start date: September 27, 2020
• Est. completion date: December 2027

Study information

• Verified date: February 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: Jessica Crimella, BSN, RN
• Phone: 813-745-6250
• Email: Jessica.Crimella[@]moffitt.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: December 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Rhabdomyosarcoma

Intervention

Drug:
• Vincristine
IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg
• Cyclophosphamide
IV over 60 minutes with dosing ranging from 220mg to 1200mg
• Vinorelbine
IV push over 6-10 minutes with dosing ranging from 4mg-25mg
• Actinomycin D
Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg
• Cyclophosphamide Pill
Based on Body Surface Area (BSA) round to nearest 25mg

Locations

Country	Name	City	State
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Montefiore Medical Cancer Center	Bronx	New York
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of North Carolina Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Carolinas Medical Center, Levine Cancer Institute	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke Children's Hospital	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	MD Anderson	Houston	Texas
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Medical Center/Utah	Salt Lake City	Utah
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	National Pediatric Cancer Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First Strike Event Free Survival	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.	Baseline to 3 years
Primary	Second Strike Event Free Survival	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	Baseline to 3 years
Primary	Adaptive Therapy Event Free Survival	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	Baseline to 3 years
Secondary	Overall Survival	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	5 years
Secondary	Treatment-related adverse events of a certain grade or higher	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	Baseline to 5 years

External Links

•   Moffitt Cancer Center Clinical Trials Website