A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High 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:
- Patients must be =< 50 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. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (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). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants
ERMS
- Stage 4, group IV, >= 10 years of age
ARMS
- Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age
- Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
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 (must be performed within 7 days prior to enrollment):
- Age; Maximum serum creatinine (mg/dL)
- 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
- 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
- 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
- 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
- 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
- 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
- 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
- >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
- If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x 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 with evidence of uncontrolled infection are not eligible
- RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed
Patients with central nervous system involvement of RMS as defined below:
- Malignant cells detected in cerebrospinal fluid
- Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed).
- Diffuse leptomeningeal disease
Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment.
Note: the following exception:
- Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation
- Note: Patients who have received or are receiving chemotherapy or radiation for non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy
- Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
- Lactating females who plan to breastfeed their infants
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Sites / Locations
- Children's Hospital of AlabamaRecruiting
- USA Health Strada Patient Care CenterRecruiting
- Providence Alaska Medical CenterRecruiting
- Kingman Regional Medical CenterRecruiting
- Banner Children's at DesertRecruiting
- Phoenix Childrens HospitalRecruiting
- Banner University Medical Center - TucsonRecruiting
- Arkansas Children's HospitalRecruiting
- PCR OncologyRecruiting
- City of Hope Comprehensive Cancer CenterRecruiting
- Loma Linda University Medical CenterRecruiting
- Miller Children's and Women's Hospital Long BeachRecruiting
- Children's Hospital Los AngelesRecruiting
- Cedars Sinai Medical CenterRecruiting
- Mattel Children's Hospital UCLARecruiting
- Valley Children's HospitalRecruiting
- UCSF Benioff Children's Hospital OaklandRecruiting
- Kaiser Permanente-OaklandRecruiting
- Children's Hospital of Orange CountyRecruiting
- Lucile Packard Children's Hospital Stanford UniversityRecruiting
- University of California Davis Comprehensive Cancer CenterRecruiting
- Rady Children's Hospital - San DiegoRecruiting
- Naval Medical Center -San DiegoRecruiting
- UCSF Medical Center-Mission BayRecruiting
- Children's Hospital ColoradoRecruiting
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterRecruiting
- Connecticut Children's Medical CenterRecruiting
- Smilow Cancer Center/Yale-New Haven HospitalRecruiting
- Yale UniversityRecruiting
- Alfred I duPont Hospital for ChildrenRecruiting
- MedStar Georgetown University Hospital
- Children's National Medical CenterRecruiting
- Broward Health Medical CenterRecruiting
- Golisano Children's Hospital of Southwest FloridaRecruiting
- University of Florida Health Science Center - GainesvilleRecruiting
- Memorial Regional Hospital/Joe DiMaggio Children's HospitalRecruiting
- Nemours Children's Clinic-JacksonvilleRecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
- Nicklaus Children's HospitalRecruiting
- Arnold Palmer Hospital for ChildrenRecruiting
- Nemours Children's HospitalRecruiting
- Sacred Heart HospitalRecruiting
- Tampa General HospitalRecruiting
- Saint Joseph's Hospital/Children's Hospital-TampaRecruiting
- Saint Mary's HospitalRecruiting
- Children's Healthcare of Atlanta - EglestonRecruiting
- Medical Center of Central GeorgiaRecruiting
- Memorial Health University Medical CenterRecruiting
- Kapiolani Medical Center for Women and ChildrenRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Lurie Children's Hospital-ChicagoRecruiting
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Loyola University Medical CenterRecruiting
- Advocate Children's Hospital-Oak LawnRecruiting
- Advocate Children's Hospital-Park RidgeRecruiting
- Saint Jude Midwest AffiliateRecruiting
- Saint John's HospitalRecruiting
- Southern Illinois University School of MedicineRecruiting
- Northwestern Medicine Central DuPage HospitalRecruiting
- Riley Hospital for ChildrenRecruiting
- Ascension Saint Vincent Indianapolis HospitalRecruiting
- Blank Children's HospitalRecruiting
- University of Iowa/Holden Comprehensive Cancer CenterRecruiting
- University of Kentucky/Markey Cancer CenterRecruiting
- Norton Children's HospitalRecruiting
- Children's Hospital New OrleansRecruiting
- Ochsner Medical Center JeffersonRecruiting
- Eastern Maine Medical Center
- Maine Children's Cancer ProgramRecruiting
- Sinai Hospital of BaltimoreRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Walter Reed National Military Medical Center
- Tufts Children's Hospital
- Tufts Medical Center
- Massachusetts General Hospital Cancer CenterRecruiting
- Dana-Farber Cancer InstituteRecruiting
- UMass Memorial Medical Center - University CampusRecruiting
- C S Mott Children's HospitalRecruiting
- Bronson Battle CreekRecruiting
- Children's Hospital of MichiganRecruiting
- Michigan State University Clinical CenterRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Spectrum Health at Butterworth CampusRecruiting
- Trinity Health Grand Rapids HospitalRecruiting
- Bronson Methodist HospitalRecruiting
- West Michigan Cancer CenterRecruiting
- Borgess Medical CenterRecruiting
- Trinity Health Muskegon HospitalRecruiting
- Lakeland Hospital NilesRecruiting
- Cancer and Hematology Centers of Western Michigan - Norton ShoresRecruiting
- Spectrum Health Reed City HospitalRecruiting
- Beaumont Children's Hospital-Royal OakRecruiting
- Lakeland Medical Center Saint JosephRecruiting
- Marie Yeager Cancer CenterRecruiting
- Munson Medical CenterRecruiting
- University of Michigan Health - WestRecruiting
- Children's Hospitals and Clinics of Minnesota - MinneapolisRecruiting
- University of Minnesota/Masonic Cancer CenterRecruiting
- Mayo Clinic in RochesterRecruiting
- University of Mississippi Medical CenterRecruiting
- Columbia RegionalRecruiting
- Children's Mercy Hospitals and ClinicsRecruiting
- Cardinal Glennon Children's Medical CenterRecruiting
- Washington University School of MedicineRecruiting
- Mercy Hospital Saint LouisRecruiting
- Children's Hospital and Medical Center of OmahaRecruiting
- University of Nebraska Medical CenterRecruiting
- Comprehensive Cancer Centers of Nevada - HendersonRecruiting
- OptumCare Cancer Care at Seven HillsRecruiting
- OptumCare Cancer Care at CharlestonRecruiting
- Radiation Oncology Centers of Nevada CentralRecruiting
- GenesisCare USA - Las VegasRecruiting
- Radiation Oncology Centers of Nevada SoutheastRecruiting
- Comprehensive Cancer Centers of Nevada - NorthwestRecruiting
- OptumCare Cancer Care at MountainViewRecruiting
- Alliance for Childhood Diseases/Cure 4 the Kids FoundationRecruiting
- Comprehensive Cancer Centers of Nevada - Town CenterRecruiting
- Comprehensive Cancer Centers of Nevada-SummerlinRecruiting
- Comprehensive Cancer Centers of NevadaRecruiting
- GenesisCare USA - Fort ApacheRecruiting
- OptumCare Cancer Care at Fort ApacheRecruiting
- Comprehensive Cancer Centers of Nevada - Central ValleyRecruiting
- Renown Regional Medical CenterRecruiting
- Saint Mary's Regional Medical CenterRecruiting
- Radiation Oncology AssociatesRecruiting
- Cancer Care Specialists - Reno
- Hackensack University Medical CenterRecruiting
- Morristown Medical CenterRecruiting
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University HospitalRecruiting
- Newark Beth Israel Medical CenterRecruiting
- Saint Joseph's Regional Medical CenterRecruiting
- Albany Medical CenterRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Maimonides Medical CenterRecruiting
- Roswell Park Cancer InstituteRecruiting
- The Steven and Alexandra Cohen Children's Medical Center of New YorkRecruiting
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- NYP/Weill Cornell Medical CenterRecruiting
- Stony Brook University Medical CenterRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- New York Medical CollegeRecruiting
- Westchester Medical CenterRecruiting
- Mission HospitalRecruiting
- Carolinas Medical Center/Levine Cancer InstituteRecruiting
- Novant Health Presbyterian Medical CenterRecruiting
- East Carolina UniversityRecruiting
- Wake Forest University Health SciencesRecruiting
- Sanford Broadway Medical CenterRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- Rainbow Babies and Childrens HospitalRecruiting
- Cleveland Clinic FoundationRecruiting
- Nationwide Children's HospitalRecruiting
- Dayton Children's HospitalRecruiting
- ProMedica Flower HospitalRecruiting
- ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Legacy Emanuel Children's HospitalRecruiting
- Oregon Health and Science UniversityRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Geisinger Medical CenterRecruiting
- Penn State Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Children's Oncology Group
- Saint Christopher's Hospital for ChildrenRecruiting
- Children's Hospital of Pittsburgh of UPMCRecruiting
- Rhode Island HospitalRecruiting
- Prisma Health Richland HospitalRecruiting
- BI-LO Charities Children's Cancer CenterRecruiting
- Prisma Health Cancer Institute - FarisRecruiting
- Prisma Health Cancer Institute - EastsideRecruiting
- Prisma Health Cancer Institute - GreerRecruiting
- Prisma Health Cancer Institute - SenecaRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- T C Thompson Children's HospitalRecruiting
- East Tennessee Childrens HospitalRecruiting
- Saint Jude Children's Research HospitalRecruiting
- The Children's Hospital at TriStar CentennialRecruiting
- Vanderbilt University/Ingram Cancer CenterRecruiting
- Texas Tech University Health Sciences Center-AmarilloRecruiting
- Dell Children's Medical Center of Central TexasRecruiting
- Driscoll Children's HospitalRecruiting
- Medical City Dallas HospitalRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- El Paso Children's HospitalRecruiting
- Cook Children's Medical CenterRecruiting
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
- M D Anderson Cancer CenterRecruiting
- Covenant Children's HospitalRecruiting
- UMC Cancer Center / UMC Health SystemRecruiting
- Children's Hospital of San AntonioRecruiting
- Methodist Children's Hospital of South TexasRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Scott and White Memorial HospitalRecruiting
- Primary Children's HospitalRecruiting
- University of Vermont and State Agricultural CollegeRecruiting
- University of Virginia Cancer CenterRecruiting
- Inova Fairfax HospitalRecruiting
- Children's Hospital of The King's DaughtersRecruiting
- Naval Medical Center - PortsmouthRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Carilion Children'sRecruiting
- Overlake Medical Center
- Valley Medical CenterRecruiting
- Seattle Children's HospitalRecruiting
- Providence Sacred Heart Medical Center and Children's HospitalRecruiting
- Mary Bridge Children's Hospital and Health CenterRecruiting
- Madigan Army Medical CenterRecruiting
- North Star Lodge Cancer Center at Yakima Valley Memorial HospitalRecruiting
- West Virginia University Charleston DivisionRecruiting
- Saint Vincent Hospital Cancer Center Green BayRecruiting
- Saint Vincent Hospital Cancer Center at Saint Mary'sRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Medical College of WisconsinRecruiting
- John Hunter Children's HospitalRecruiting
- The Children's Hospital at WestmeadRecruiting
- Royal Children's Hospital
- Perth Children's HospitalRecruiting
- Alberta Children's HospitalRecruiting
- University of Alberta HospitalRecruiting
- CancerCare ManitobaRecruiting
- IWK Health CentreRecruiting
- McMaster Children's Hospital at Hamilton Health SciencesRecruiting
- Kingston Health Sciences CentreRecruiting
- Children's HospitalRecruiting
- Children's Hospital of Eastern OntarioRecruiting
- Hospital for Sick ChildrenRecruiting
- The Montreal Children's Hospital of the MUHCRecruiting
- Centre Hospitalier Universitaire Sainte-JustineRecruiting
- Jim Pattison Children's Hospital
- Saskatoon Cancer Centre
- Centre Hospitalier Universitaire de QuebecRecruiting
- HIMA San Pablo Oncologic HospitalRecruiting
- King Faisal Specialist Hospital and Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A (VAC, VINO-CPO)
Arm B (vinorelbine, VAC, VINO-CPO)
Patients receive vincristine sulfate IV on days 1, 8 and 15 of cycles 1-4, 7, 8, 11, and 12, and day 1 of cycles 5, 6, 9, 10, 13, and 14. Patients also receive dactinomycin IV over 1-15 minutes or IVP over 1-5 minutes on day 1 of cycles 1-5, 8-10, and 11-14, and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on weeks 13 and 40. MAINTENANCE: Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15, and cyclophosphamide PO on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients in both arms undergo CT, MRI, PET, x-ray imaging, and/or bone scan, as well as blood sample collection throughout the trial. Patients may also undergo bone marrow aspiration and/or biopsy as clinically indicated.
Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8, vincristine sulfate IV on day 15, dactinomycin IV over 1-15 minutes or IVP over 1-5 minutes on day 1 of cycles 1-5 and 8-14, and cyclophosphamide IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on weeks 13 and 40. MAINTENANCE: Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15, and cyclophosphamide PO on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients in both arms undergo CT, MRI, PET, x-ray imaging, and/or bone scan, as well as blood sample collection throughout the trial. Patients may also undergo bone marrow aspiration and/or biopsy as clinically indicated.