Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma
About this trial
This is an interventional treatment trial for Alveolar Rhabdomyosarcoma
Eligibility Criteria
Inclusion Criteria:
- Feasibility Phase: Patients must be < 21 years of age at the time of enrollment; please note: the feasibility phase is complete, effective with amendment #1
- Efficacy Phase: Patients must be =< 40 years of age at the time of enrollment
- Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study based upon stage, group, and age, as below
RMS types included under embryonal rhabdomyosarcoma (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 2013 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); classification of alveolar rhabdomyosarcoma (ARMS) in the 2013 WHO classification is the same as in the ICR and includes classic and solid variants
ERMS
- Stage 1, group III (non-orbit)
- Stage 3, group I/II
- Stage 2/3, group III
- Stage 4, group IV, < 10 years old
ARMS:
- Stages 1-3, groups I-III
- Specimen Submission: Patients must have sufficient tissue available for the required biology study
- Lansky performance status score >= 50 for patients =< 16 years of age; Karnofsky performance status score >= 50 for patients > 16 years of age
- Peripheral absolute neutrophil count (ANC) >= 750/uL
- Platelet count >= 75,000/uL
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- 1 month to < 6 months old: 0.4 mg/dl (male), 0.4 mg/dl (female)
- 6 months to < 1 year old: 0.5 mg/dl (male), 0.5 mg/dl (female)
- 1 to < 2 years old: 0.6 mg/dl (male), 0.6 mg/dl (female)
- 2 to < 6 years old: 0.8 mg/dl (male), 0.8 mg/dl (female)
- 6 to < 10 years old: 1 mg/dl (male), 1 mg/dl (female)
- 10 to < 13 years old: 1.2 mg/dl (male), 1.2 mg/dl (female)
- 13 to < 16 years old: 1.5 mg/dl (male), 1.4 mg/dl (female)
- >= 16 years old: 1.7 mg/dl (male), 1.4 mg/dl (female)
- Patients with an elevated serum creatinine due to obstructive hydronephrosis secondary to tumor are still eligible; however, patients with urinary tract obstruction by tumor must have unimpeded urinary flow established via diversion (i.e. percutaneous nephrostomies or ureteric stents) of the urinary tract
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
- 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.
Exclusion Criteria:
- Patients who have previously received temsirolimus, another mTOR inhibitor, or any other investigational agent
- Patients who have received any chemotherapy (excluding steroids) and/or RT prior to this enrollment
- Patients with uncontrolled hyperglycemia
- Patients with uncontrolled hyperlipidemia
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for at least 3 months after treatment is completed
- Female patients who are pregnant are not eligible since fetal toxicities or teratogenic effects have been noted for several of the study drugs; Note: A pregnancy test is required for female patients of childbearing potential prior to study entry
- Lactating females who plan to breastfeed their infants are not eligible
Sites / Locations
- Children's Hospital of Alabama
- USA Health Strada Patient Care Center
- Anchorage Associates in Radiation Medicine
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Kingman Regional Medical Center
- Banner Children's at Desert
- Phoenix Childrens Hospital
- Mayo Clinic Hospital in Arizona
- Mayo Clinic in Arizona
- Banner University Medical Center - Tucson
- Arkansas Children's Hospital
- Kaiser Permanente-Anaheim
- PCR Oncology
- Kaiser Permanente-Bellflower
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Kaiser Permanente Downey Medical Center
- Kaiser Permanente-Fontana
- Loma Linda University Medical Center
- Children's Hospital Los Angeles
- Kaiser Permanente Los Angeles Medical Center
- Mattel Children's Hospital UCLA
- UCLA / Jonsson Comprehensive Cancer Center
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Kaiser Permanente-Oakland
- Children's Hospital of Orange County
- Lucile Packard Children's Hospital Stanford University
- Kaiser Permanente-Roseville
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Kaiser Permanente-San Diego Mission
- Rady Children's Hospital - San Diego
- Naval Medical Center -San Diego
- UCSF Medical Center-Mission Bay
- Kaiser Permanente Medical Center - Santa Clara
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Children's Hospital Colorado
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
- Connecticut Children's Medical Center
- Smilow Cancer Center/Yale-New Haven Hospital
- Yale University
- Smilow Cancer Hospital Care Center-Trumbull
- Alfred I duPont Hospital for Children
- Kaiser Permanente-Capitol Hill Medical Center
- MedStar Georgetown University Hospital
- Children's National Medical Center
- Sibley Memorial Hospital
- Broward Health Medical Center
- Golisano Children's Hospital of Southwest Florida
- University of Florida Health Science Center - Gainesville
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Nemours Children's Clinic-Jacksonville
- Palms West Radiation Therapy
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's Hospital
- Miami Cancer Institute
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Nemours Children's Hospital
- Nemours Children's Clinic - Pensacola
- Sacred Heart Hospital
- Johns Hopkins All Children's Hospital
- Tampa General Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Augusta University Medical Center
- Medical Center of Central Georgia
- Memorial Health University Medical Center
- Straub Clinic and Hospital
- Kaiser Permanente Moanalua Medical Center
- Kapiolani Medical Center for Women and Children
- Saint Luke's Cancer Institute - Boise
- Saint Luke's Cancer Institute - Fruitland
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Luke's Cancer Institute - Twin Falls
- Lurie Children's Hospital-Chicago
- John H Stroger Jr Hospital of Cook County
- Rush University Medical Center
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Loyola University Medical Center
- Advocate Children's Hospital-Oak Lawn
- Advocate Children's Hospital-Park Ridge
- Saint Jude Midwest Affiliate
- Saint John's Hospital
- Southern Illinois University School of Medicine
- Memorial Medical Center
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- Blank Children's Hospital
- Iowa Methodist Medical Center
- Iowa Lutheran Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Children's Hospital New Orleans
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Maine Children's Cancer Program
- University of Maryland/Greenebaum Cancer Center
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Tufts Children's Hospital
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- UMass Memorial Medical Center - University Campus
- C S Mott Children's Hospital
- University of Michigan Comprehensive Cancer Center
- Bronson Battle Creek
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Michigan State University Clinical Center
- Hurley Medical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Trinity Health Muskegon Hospital
- Lakeland Hospital Niles
- Huron Medical Center PC
- Lake Huron Medical Center
- Spectrum Health Reed City Hospital
- Beaumont Children's Hospital-Royal Oak
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Munson Medical Center
- University of Michigan Health - West
- Essentia Health Cancer Center
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Columbia Regional
- Siteman Cancer Center at West County Hospital
- Children's Mercy Hospitals and Clinics
- Cardinal Glennon Children's Medical Center
- Barnes-Jewish Hospital
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Siteman Cancer Center at Saint Peters Hospital
- Saint Patrick Hospital - Community Hospital
- Children's Hospital and Medical Center of Omaha
- University of Nebraska Medical Center
- Carson Tahoe Regional Medical Center
- Cancer and Blood Specialists-Henderson
- Comprehensive Cancer Centers of Nevada - Henderson
- Comprehensive Cancer Centers of Nevada-Horizon Ridge
- Las Vegas Cancer Center-Henderson
- OptumCare Cancer Care at Seven Hills
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
- GenesisCare USA - Henderson
- Las Vegas Urology - Green Valley
- Las Vegas Urology - Pebble
- Urology Specialists of Nevada - Green Valley
- Las Vegas Urology - Pecos
- Desert West Surgery
- OptumCare Cancer Care at Charleston
- University Medical Center of Southern Nevada
- Cancer and Blood Specialists-Shadow
- Radiation Oncology Centers of Nevada Central
- Urology Specialists of Nevada - Central
- GenesisCare USA - Las Vegas
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
- Sunrise Hospital and Medical Center
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
- Las Vegas Urology - Sunset
- Urology Specialists of Nevada - Southwest
- Radiation Oncology Centers of Nevada Southeast
- Cancer Therapy and Integrative Medicine
- Ann M Wierman MD LTD
- Cancer and Blood Specialists-Tenaya
- Comprehensive Cancer Centers of Nevada - Northwest
- GenesisCare USA - Vegas Tenaya
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
- Las Vegas Urology - Cathedral Rock
- Las Vegas Urology - Smoke Ranch
- OptumCare Cancer Care at MountainView
- Urology Specialists of Nevada - Northwest
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Comprehensive Cancer Centers of Nevada - Town Center
- Comprehensive Cancer Centers of Nevada-Summerlin
- Summerlin Hospital Medical Center
- Las Vegas Cancer Center-Medical Center
- Comprehensive Cancer Centers of Nevada
- GenesisCare USA - Fort Apache
- OptumCare Cancer Care at Fort Apache
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
- Comprehensive Cancer Centers of Nevada - Central Valley
- University Cancer Center
- Hope Cancer Care of Nevada-Pahrump
- Renown Regional Medical Center
- Saint Mary's Regional Medical Center
- Radiation Oncology Associates
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Hackensack University Medical Center
- Morristown Medical Center
- Saint Peter's University Hospital
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Rutgers Cancer Institute of New Jersey
- Newark Beth Israel Medical Center
- Saint Joseph's Regional Medical Center
- Presbyterian Hospital
- Albany Medical Center
- Montefiore Medical Center-Einstein Campus
- Montefiore Medical Center-Weiler Hospital
- Children's Hospital at Montefiore
- Montefiore Medical Center - Moses Campus
- Maimonides Medical Center
- Roswell Park Cancer Institute
- Glens Falls Hospital
- NYU Winthrop Hospital
- The Steven and Alexandra Cohen Children's Medical Center of New York
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- New York Medical College
- Westchester Medical Center
- Mission Hospital
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Novant Health Carolina Surgical - Randolph
- Oncology Specialists of Charlotte
- Southern Oncology Specialists-Charlotte
- Duke University Medical Center
- East Carolina University
- Novant Health Cancer Institute - Huntersville
- Novant Health Presbyterian Medical Center Huntersville
- Southern Oncology Specialists-Huntersville
- Matthews Radiation Oncology Center
- Novant Health Cancer Institute - Matthews
- Lake Norman Radiation Oncology Center-Mooresville
- Novant Health Cancer Institute - Mooresville
- Novant Health Cancer Institute - Rowan
- Rowan Regional Medical Center
- Wake Forest University Health Sciences
- Sanford Broadway Medical Center
- Children's Hospital Medical Center of Akron
- Cincinnati Children's Hospital Medical Center
- Rainbow Babies and Childrens Hospital
- Cleveland Clinic Foundation
- Nationwide Children's Hospital
- Dayton Children's Hospital
- ProMedica Flower Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University of Oklahoma Health Sciences Center
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Providence Newberg Medical Center
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Legacy Emanuel Children's Hospital
- Oregon Health and Science University
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Penn State Children's Hospital
- Children's Hospital of Philadelphia
- Saint Christopher's Hospital for Children
- Children's Hospital of Pittsburgh of UPMC
- Rhode Island Hospital
- Prisma Health Cancer Institute - Spartanburg
- Medical University of South Carolina
- Prisma Health Cancer Institute - Laurens
- Prisma Health Richland Hospital
- Prisma Health Cancer Institute - Easley
- Saint Francis Hospital
- BI-LO Charities Children's Cancer Center
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Saint Francis Cancer Center
- Prisma Health Cancer Institute - Eastside
- Prisma Health Cancer Institute - Greer
- Prisma Health Cancer Institute - Seneca
- Sanford USD Medical Center - Sioux Falls
- T C Thompson Children's Hospital
- East Tennessee Childrens Hospital
- The Children's Hospital at TriStar Centennial
- Vanderbilt University/Ingram Cancer Center
- Texas Tech University Health Sciences Center-Amarillo
- Dell Children's Medical Center of Central Texas
- Driscoll Children's Hospital
- Medical City Dallas Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- El Paso Children's Hospital
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- M D Anderson Cancer Center
- Covenant Children's Hospital
- UMC Cancer Center / UMC Health System
- Texas Tech University Health Sciences Center-Lubbock
- Children's Hospital of San Antonio
- Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
- Methodist Children's Hospital of South Texas
- University Hospital
- University of Texas Health Science Center at San Antonio
- Scott and White Memorial Hospital
- Primary Children's Hospital
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont Medical Center
- University of Vermont and State Agricultural College
- University of Virginia Cancer Center
- Inova Fairfax Hospital
- Children's Hospital of The King's Daughters
- Naval Medical Center - Portsmouth
- Virginia Commonwealth University/Massey Cancer Center
- Providence Regional Cancer System-Aberdeen
- Overlake Medical Center
- PeaceHealth Saint Joseph Medical Center
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Providence Regional Cancer Partnership
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and Oncology
- Providence Regional Cancer System-Lacey
- PeaceHealth Saint John Medical Center
- Pacific Gynecology Specialists
- Seattle Children's Hospital
- Swedish Medical Center-Ballard Campus
- Kaiser Permanente Washington
- Swedish Medical Center-Cherry Hill
- Swedish Medical Center-First Hill
- University of Washington Medical Center - Montlake
- Providence Regional Cancer System-Shelton
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
- Providence Sacred Heart Medical Center and Children's Hospital
- MultiCare Deaconess Cancer and Blood Specialty Center - North
- Mary Bridge Children's Hospital and Health Center
- Madigan Army Medical Center
- PeaceHealth Southwest Medical Center
- Providence Saint Mary Regional Cancer Center
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- Providence Regional Cancer System-Yelm
- United Hospital Center
- West Virginia University Charleston Division
- WVUH-Berkely Medical Center
- West Virginia University Healthcare
- Camden Clark Medical Center
- Gundersen Lutheran Medical Center
- University of Wisconsin Carbone Cancer Center
- Marshfield Medical Center-Marshfield
- Children's Hospital of Wisconsin
- John Hunter Children's Hospital
- Sydney Children's Hospital
- The Children's Hospital at Westmead
- Queensland Children's Hospital
- Princess Margaret Hospital for Children
- Perth Children's Hospital
- Alberta Children's Hospital
- University of Alberta Hospital
- British Columbia Children's Hospital
- CancerCare Manitoba
- Janeway Child Health Centre
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- Kingston Health Sciences Centre
- Children's Hospital
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- Jim Pattison Children's Hospital
- Saskatoon Cancer Centre
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
- Starship Children's Hospital
- Christchurch Hospital
- HIMA San Pablo Oncologic Hospital
- San Jorge Children's Hospital
- University Pediatric Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Regimen A (VAC/VI)
Regimen B (VAC/VI/temsirolimus)
Regimen C (FOXO1 fusion negative, VAC/VA)
Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. Patients also undergo primary site RT beginning at week 13 or metastatic site RT beginning at week 43 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide PO QD on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.
Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37 and temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. Patients also undergo RT as in Regimen A. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide PO QD on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.
Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients undergo RT beginning at week 13 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.