A Prospective Phase 3 Study of Patients With Newly Diagnosed Very Low-Risk and Low-Risk Fusion Negative Rhabdomyosarcoma

Status: Recruiting
Location: See all (81) locations...
Intervention Type: Drug, Radiation, Biological
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.

Eligibility
Participation Requirements
Sex: All
Maximum Age: 21
Healthy Volunteers: No
View:

• All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial).

• Patients must be =< 21 years at the time of enrollment.

• Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients.

• All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed.

• Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease.

• Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease.

• Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients >= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging.

• Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors.

• Clinically or radiographically enlarged nodes must be sampled for histologic evaluation.

• Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for patients > 16 years of age) performance status score of >= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.

• Peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to enrollment).

• Platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows:

• Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female)

• Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female)

• Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)

• Age >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and

• If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be < 3 x ULN for age.

• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment).

• All patients and/or their parents or legal guardians must sign a written informed consent.

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Locations
United States
Alabama
Children's Hospital of Alabama
Recruiting
Birmingham
Arkansas
Arkansas Children's Hospital
Recruiting
Little Rock
California
Loma Linda University Medical Center
Recruiting
Loma Linda
Children's Hospital Los Angeles
Recruiting
Los Angeles
Valley Children's Hospital
Recruiting
Madera
Children's Hospital of Orange County
Recruiting
Orange
UCSF Medical Center-Mission Bay
Recruiting
San Francisco
Colorado
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Recruiting
Denver
Connecticut
Connecticut Children's Medical Center
Recruiting
Hartford
Delaware
Alfred I duPont Hospital for Children
Recruiting
Wilmington
Florida
Golisano Children's Hospital of Southwest Florida
Recruiting
Fort Myers
University of Florida Health Science Center - Gainesville
Recruiting
Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Recruiting
Hollywood
Nemours Children's Clinic-Jacksonville
Recruiting
Jacksonville
Nemours Children's Hospital
Recruiting
Orlando
Sacred Heart Hospital
Recruiting
Pensacola
Johns Hopkins All Children's Hospital
Recruiting
Saint Petersburg
Saint Joseph's Hospital/Children's Hospital-Tampa
Recruiting
Tampa
Iowa
University of Iowa/Holden Comprehensive Cancer Center
Recruiting
Iowa City
Illinois
Lurie Children's Hospital-Chicago
Recruiting
Chicago
Advocate Children's Hospital-Oak Lawn
Recruiting
Oak Lawn
Advocate Children's Hospital-Park Ridge
Recruiting
Park Ridge
Saint Jude Midwest Affiliate
Recruiting
Peoria
Southern Illinois University School of Medicine
Recruiting
Springfield
Indiana
Ascension Saint Vincent Indianapolis Hospital
Recruiting
Indianapolis
Riley Hospital for Children
Recruiting
Indianapolis
Kentucky
Norton Children's Hospital
Recruiting
Louisville
Louisiana
Ochsner Medical Center Jefferson
Recruiting
New Orleans
Massachusetts
Dana-Farber Cancer Institute
Recruiting
Boston
UMass Memorial Medical Center - University Campus
Recruiting
Worcester
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Recruiting
Baltimore
Sinai Hospital of Baltimore
Recruiting
Baltimore
Maine
Maine Children's Cancer Program
Recruiting
Scarborough
Michigan
C S Mott Children's Hospital
Recruiting
Ann Arbor
Helen DeVos Children's Hospital at Spectrum Health
Recruiting
Grand Rapids
Bronson Methodist Hospital
Recruiting
Kalamazoo
Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Recruiting
Minneapolis
Mayo Clinic in Rochester
Not yet recruiting
Rochester
Missouri
Children's Mercy Hospitals and Clinics
Recruiting
Kansas City
Mercy Hospital Saint Louis
Recruiting
Saint Louis
Washington University School of Medicine
Recruiting
Saint Louis
Mississippi
University of Mississippi Medical Center
Recruiting
Jackson
Nebraska
Children's Hospital and Medical Center of Omaha
Recruiting
Omaha
University of Nebraska Medical Center
Recruiting
Omaha
New Jersey
Hackensack University Medical Center
Recruiting
Hackensack
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Recruiting
New Brunswick
New York
Albany Medical Center
Recruiting
Albany
Montefiore Medical Center - Moses Campus
Recruiting
Bronx
Memorial Sloan Kettering Cancer Center
Recruiting
New York
State University of New York Upstate Medical University
Recruiting
Syracuse
Ohio
Cincinnati Children's Hospital Medical Center
Recruiting
Cincinnati
Rainbow Babies and Childrens Hospital
Recruiting
Cleveland
Dayton Children's Hospital
Recruiting
Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Recruiting
Toledo
Oregon
Oregon Health and Science University
Recruiting
Portland
Pennsylvania
Geisinger Medical Center
Recruiting
Danville
Children's Hospital of Pittsburgh of UPMC
Recruiting
Pittsburgh
South Carolina
Prisma Health Richland Hospital
Recruiting
Columbia
BI-LO Charities Children's Cancer Center
Recruiting
Greenville
Tennessee
The Children's Hospital at TriStar Centennial
Recruiting
Nashville
Vanderbilt University/Ingram Cancer Center
Recruiting
Nashville
Texas
Medical City Dallas Hospital
Recruiting
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
Recruiting
Dallas
El Paso Children's Hospital
Recruiting
El Paso
Cook Children's Medical Center
Recruiting
Fort Worth
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Recruiting
Houston
M D Anderson Cancer Center
Recruiting
Houston
Children's Hospital of San Antonio
Recruiting
San Antonio
University of Texas Health Science Center at San Antonio
Recruiting
San Antonio
Utah
Primary Children's Hospital
Recruiting
Salt Lake City
Virginia
Inova Fairfax Hospital
Recruiting
Falls Church
Children's Hospital of The King's Daughters
Recruiting
Norfolk
Washington
Seattle Children's Hospital
Recruiting
Seattle
Providence Sacred Heart Medical Center and Children's Hospital
Recruiting
Spokane
Madigan Army Medical Center
Recruiting
Tacoma
Wisconsin
University of Wisconsin Carbone Cancer Center
Recruiting
Madison
Marshfield Medical Center-Marshfield
Recruiting
Marshfield
West Virginia
West Virginia University Charleston Division
Recruiting
Charleston
Other Locations
Australia
Perth Children's Hospital
Recruiting
Perth
The Children's Hospital at Westmead
Recruiting
Westmead
Canada
IWK Health Centre
Recruiting
Halifax
Time Frame
Start Date: June 22, 2022
Estimated Completion Date: December 30, 2041
Participants
Target number of participants: 205
Treatments
Experimental: Regimen M (positive mutation)
Patients receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 2-4, 7-8, and 11-12 and dactinomycin IV over 1-5 minutes or 10-15 minutes on day 1 of cycles 2-5 and 8-14. Patients also receive cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 12-13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo radiation therapy at cycle 5.
Experimental: Regimen VA (VLR RMS)
Patients with VLR RMS receive vincristine intravenously (IV) on day 1 of each cycle and days 8 and 15 of cycles 1, 3, 5, and 7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3).
Experimental: Regimen VAC/VA (VL RMS)
Patients with LR RMS receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 1-3. Patients also receive dactinomycin IV over 1-5 minutes or 10-15 minutes and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 5-7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Radiation therapy (if needed) will be administered at cycle 5.
Sponsors
Leads: Children's Oncology Group
Collaborators: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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