Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma
Brain and Central Nervous System Tumors
About this trial
This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma
Eligibility Criteria
Pre-Registration Inclusion Criteria:
United States (US) and Canadian sites:
* This review is mandatory prior to registration to confirm eligibility; patients must be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible
Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation prior to submission for central path review
- Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility, the 1p/19q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for US, must be Clinical Laboratory Improvement Act [CLIA] certified); acceptable methods for determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by genomic sequencing or methylomic analyses; US and Canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (QAS)
- Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (US: performed in a CLIA certified laboratory); the site must send a copy of the official report to the pathology coordinator and QAS
Registration Inclusion Criteria:
- Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure > 3 months earlier for low grade glioma, as long as the patient has not received prior radiation or prior chemotherapy
Histological evidence of World Health Organization (WHO) grade III anaplastic glioma or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either IDH1 or IDH2, both as established by a local or referenced laboratory qualified for the study
* Note: mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q
Patients with codeleted low grade gliomas must also be considered "high risk" by exhibiting one or more of the following characteristics:
- Age >= 40 and any surgical therapy
- Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than gross total resection)
- Documented growth following prior surgery (NOTE: patients with prior surgery cannot have received prior radiation, chemotherapy or targeted therapy)
- Intractable seizures
- Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks prior to registration; patient must have recovered adequately from the effects of surgery
- Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior to registration
- Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration
- Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21 days prior to registration
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN obtained =< 21 days prior to registration
- Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration
- Negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the QOL testing, (either personally or with assistance)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
- Written informed consent
- Willingness to return to enrolling institution for follow-up during the active monitoring phase (that is, the active treatment and observation portion) of the study); patients who have been formally transferred to another active and approved site participating in this study would not need to return to the enrolling institution for this purpose
- Willingness to allow the provision of tissue samples for correlative research, as long as adequate tissues are available; patients will not be excluded from participation in the study, if they are willing to allow provision of tissues for the correlative research, but there are insufficient quantities of tissue for the correlative analyses (e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to allow the provision of blood samples for correlative research; patients are not excluded from participation in the study, if they are willing to provide the mandatory biospecimens for translational/correlative research, but for logistical reasons the specimens(s) were not obtainable or if the volume collected was insufficient
Registration Exclusion Criteria:
The following categories are ineligible:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception or contraceptive method during this study and 6 months following the completion of chemotherapy treatments
- History of prior radiation therapy or chemotherapy for glioma; note: patients who have a history of prior low grade glioma (with or without a distant history of prior surgery for that glioma), but who have never received prior chemotherapy or radiation therapy for the glioma are eligible for the study
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study
- Patients known to be human immunodeficiency virus (HIV) positive and currently receiving retroviral therapy are not eligible; note: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
- Other active malignancy within 5 years of registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, the patient is not eligible if they are receiving other specific treatment (with the exclusion of hormonal therapy or Her-2 inhibitors) for their cancer or if they have received prior total body irradiation which included the brain
- History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- Recent history of hepatitis infection or if the treating physician determined that the patient would be at significant risk of reactivation of hepatitis
Sites / Locations
- University of Alabama at Birmingham Cancer CenterRecruiting
- Providence Hospital
- Anchorage Associates in Radiation Medicine
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical CenterRecruiting
- Saint Joseph's Hospital and Medical CenterRecruiting
- Arizona Oncology-Deer Valley Center
- Arizona Oncology Services Foundation
- Kaiser Permanente-AnaheimRecruiting
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Mills-Peninsula Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Community Cancer Institute
- University Oncology Associates
- UC San Diego Moores Cancer Center
- Kaiser Permanente Los Angeles Medical CenterRecruiting
- Cedars Sinai Medical Center
- Memorial Medical Center
- Kaiser Permanente Oakland-Broadway
- Kaiser Permanente-OntarioRecruiting
- UC Irvine Health/Chao Family Comprehensive Cancer CenterRecruiting
- Sutter Cancer Centers Radiation Oncology Services-RosevilleRecruiting
- Sutter Roseville Medical Center
- Sutter Medical Center SacramentoRecruiting
- University of California Davis Comprehensive Cancer CenterRecruiting
- Kaiser Permanente Medical Center - Santa Clara
- Kaiser Permanente-South San Francisco
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- Sutter Solano Medical Center/Cancer Center
- The Medical Center of Aurora
- University of Colorado Hospital
- Penrose-Saint Francis HealthcareRecruiting
- Rocky Mountain Cancer Centers-PenroseRecruiting
- UCHealth Memorial Hospital Central
- Saint Francis Cancer CenterRecruiting
- Porter Adventist HospitalRecruiting
- Saint Anthony Hospital
- Littleton Adventist HospitalRecruiting
- Longmont United HospitalRecruiting
- McKee Medical Center
- Parker Adventist HospitalRecruiting
- Saint Mary Corwin Medical CenterRecruiting
- Yale UniversityRecruiting
- Smilow Cancer Hospital Care Center-TrumbullRecruiting
- Sibley Memorial HospitalRecruiting
- Boca Raton Regional HospitalRecruiting
- University of Florida Health Science Center - Gainesville
- Baptist MD Anderson Cancer CenterRecruiting
- Mayo Clinic in Florida
- AdventHealth OrlandoRecruiting
- Emory Proton Therapy Center
- Emory University Hospital Midtown
- Piedmont Hospital
- Emory University Hospital/Winship Cancer InstituteRecruiting
- Saint Alphonsus Cancer Care Center-CaldwellRecruiting
- Saint Alphonsus Cancer Care Center-NampaRecruiting
- Kootenai Clinic Cancer Services - Post Falls
- Illinois CancerCare-BloomingtonRecruiting
- Illinois CancerCare-CantonRecruiting
- Illinois CancerCare-CarthageRecruiting
- Centralia Oncology Clinic
- Northwestern University
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer Center
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial HospitalRecruiting
- Crossroads Cancer CenterRecruiting
- Illinois CancerCare-EurekaRecruiting
- Illinois CancerCare-GalesburgRecruiting
- Western Illinois Cancer Treatment Center
- Illinois CancerCare-Kewanee ClinicRecruiting
- AMITA Health Adventist Medical Center
- Illinois CancerCare-MacombRecruiting
- Loyola University Medical CenterRecruiting
- Cancer Care Center of O'Fallon
- Illinois CancerCare-Ottawa ClinicRecruiting
- Advocate Lutheran General Hospital
- Illinois CancerCare-PekinRecruiting
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment CenterRecruiting
- Illinois CancerCare-PeoriaRecruiting
- OSF Saint Francis Radiation Oncology at Peoria Cancer CenterRecruiting
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical CenterRecruiting
- Illinois CancerCare-PeruRecruiting
- Valley Radiation Oncology
- Illinois CancerCare-PrincetonRecruiting
- Memorial Medical CenterRecruiting
- Parkview Hospital Randallia
- Parkview Regional Medical Center
- Memorial Regional Cancer Center Day Road
- Memorial Hospital of South Bend
- McFarland Clinic - AmesRecruiting
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West LakesRecruiting
- Greater Regional Medical CenterRecruiting
- Iowa Methodist Medical CenterRecruiting
- Medical Oncology and Hematology Associates-Des Moines
- Broadlawns Medical Center
- Mercy Medical Center - Des MoinesRecruiting
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- University of Kansas Cancer CenterRecruiting
- University of Kansas Cancer Center-Overland ParkRecruiting
- University of Kansas Hospital-Indian Creek CampusRecruiting
- University of Kansas Hospital-Westwood Cancer CenterRecruiting
- University of Kentucky/Markey Cancer CenterRecruiting
- Norton Hospital Pavilion and Medical CampusRecruiting
- Norton Brownsboro Hospital and Medical CampusRecruiting
- West Jefferson Medical CenterRecruiting
- Maine Medical Center-Bramhall Campus
- Maine Medical Center- Scarborough CampusRecruiting
- Maine Medical Partners Neurology
- Maine Medical Partners - South Portland
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Walter Reed National Military Medical CenterRecruiting
- Cancer Trials Support UnitRecruiting
- Massachusetts General Hospital Cancer Center
- Bixby Medical Center
- University of Michigan Comprehensive Cancer CenterRecruiting
- Henry Ford Hospital
- Spectrum Health at Butterworth CampusRecruiting
- Trinity Health Grand Rapids Hospital
- West Michigan Cancer CenterRecruiting
- William Beaumont Hospital-Royal Oak
- Munson Medical Center
- William Beaumont Hospital - Troy
- University of Michigan Health - WestRecruiting
- Fairview Ridges Hospital
- Mercy HospitalRecruiting
- Essentia Health Cancer Center
- Miller-Dwan HospitalRecruiting
- Fairview Southdale HospitalRecruiting
- Unity HospitalRecruiting
- Minnesota Oncology Hematology PA-MaplewoodRecruiting
- Saint John's Hospital - HealtheastRecruiting
- Abbott-Northwestern HospitalRecruiting
- Hennepin County Medical CenterRecruiting
- North Memorial Medical Health CenterRecruiting
- Mayo Clinic in Rochester
- Coborn Cancer Center at Saint Cloud HospitalRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- Regions HospitalRecruiting
- United HospitalRecruiting
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical CenterRecruiting
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Saint Francis Medical CenterRecruiting
- MU Health - University Hospital/Ellis Fischel Cancer CenterRecruiting
- University of Kansas Cancer Center - NorthRecruiting
- University of Kansas Cancer Center - Lee's SummitRecruiting
- University of Kansas Cancer Center at North Kansas City HospitalRecruiting
- Washington University School of MedicineRecruiting
- Mercy Hospital Saint LouisRecruiting
- Billings Clinic Cancer CenterRecruiting
- Saint Vincent Healthcare
- Benefis Healthcare- Sletten Cancer InstituteRecruiting
- Great Falls ClinicRecruiting
- CHI Health Saint Francis
- CHI Health Good Samaritan
- Nebraska Hematology and Oncology
- Southeast Nebraska Cancer Center - 68th Street Place
- Missouri Valley Cancer ConsortiumRecruiting
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical CenterRecruiting
- Nebraska Cancer Specialists - Omaha
- Alegent Health Lakeside Hospital
- University of Nebraska Medical CenterRecruiting
- Midlands Community Hospital
- Regional West Medical Center Cancer Center
- Radiation Oncology Centers of Nevada CentralRecruiting
- GenesisCare USA - Las Vegas
- Radiation Oncology Centers of Nevada SoutheastRecruiting
- Comprehensive Cancer Centers of Nevada
- Renown Regional Medical CenterRecruiting
- Saint Mary's Regional Medical CenterRecruiting
- Radiation Oncology Associates
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Jersey Shore Medical CenterRecruiting
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Rutgers Cancer Institute of New Jersey
- Overlook Hospital
- University of New Mexico Cancer CenterRecruiting
- New York-Presbyterian/Brooklyn Methodist Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Highland Hospital
- University of RochesterRecruiting
- State University of New York Upstate Medical University
- Wake Forest University Health Sciences
- Altru Cancer Center
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer CenterRecruiting
- Riverside Methodist HospitalRecruiting
- The Mark H Zangmeister CenterRecruiting
- Mount Carmel Health Center West
- Hillcrest Hospital Cancer CenterRecruiting
- ProMedica Flower HospitalRecruiting
- Saint Ann's Hospital
- Cleveland Clinic Wooster Family Health and Surgery Center
- University of Oklahoma Health Sciences CenterRecruiting
- Oklahoma Cancer Specialists and Research Institute-TulsaRecruiting
- Clackamas Radiation Oncology Center
- Legacy Mount Hood Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar Crest
- Saint Luke's University Hospital-Bethlehem CampusRecruiting
- Geisinger Medical Center
- Saint Luke's Hospital-Anderson CampusRecruiting
- Thomas Jefferson University HospitalRecruiting
- Temple University Hospital
- Allegheny General HospitalRecruiting
- University of Pittsburgh Cancer Institute (UPCI)
- Reading HospitalRecruiting
- Geisinger Wyoming Valley/Henry Cancer Center
- Prisma Health Cancer Institute - Spartanburg
- Medical University of South CarolinaRecruiting
- Greenville Health System Cancer Institute-Andrews
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Prisma Health Cancer Institute - Eastside
- Prisma Health Cancer Institute - Greer
- Prisma Health Cancer Institute - Seneca
- Spartanburg Medical Center
- Rapid City Regional HospitalRecruiting
- Vanderbilt University/Ingram Cancer Center
- Parkland Memorial HospitalRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- University of Texas Medical Branch
- UTMB Cancer Center at Victory Lakes
- Sandra L Maxwell Cancer CenterRecruiting
- Intermountain Medical CenterRecruiting
- Utah Valley Regional Medical CenterRecruiting
- Saint George Regional Medical CenterRecruiting
- Utah Cancer Specialists-Salt Lake City
- Huntsman Cancer Institute/University of Utah
- LDS Hospital
- Norris Cotton Cancer Center-NorthRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- VCU Community Memorial Health CenterRecruiting
- PeaceHealth Saint Joseph Medical CenterRecruiting
- Kadlec Clinic Hematology and Oncology
- Tri-Cities Cancer Center
- Skagit Regional Health Cancer Care Center
- Skagit Valley Hospital
- Virginia Mason Medical Center
- FHCC South Lake Union
- Fred Hutchinson Cancer Research Center
- University of Washington Medical Center - MontlakeRecruiting
- PeaceHealth Southwest Medical CenterRecruiting
- West Virginia University Healthcare
- Northwest Wisconsin Cancer CenterRecruiting
- Gundersen Lutheran Medical CenterRecruiting
- Aurora Saint Luke's Medical Center
- Medical College of WisconsinRecruiting
- ProHealth D N Greenwald CenterRecruiting
- ProHealth Oconomowoc Memorial HospitalRecruiting
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth CareRecruiting
- Medical University ViennaRecruiting
- Alegemeen Ziekenhuis MiddelheimRecruiting
- Tom Baker Cancer CentreRecruiting
- Cross Cancer Institute
- BCCA-Vancouver Cancer CentreRecruiting
- CancerCare ManitobaRecruiting
- London Regional Cancer ProgramRecruiting
- Ottawa Hospital and Cancer Center-General Campus
- Odette Cancer Centre- Sunnybrook Health Sciences Centre
- University Health Network-Princess Margaret Hospital
- CHUM - Hopital Notre-Dame
- CHUM - Centre Hospitalier de l'Universite de MontrealRecruiting
- Allan Blair Cancer Centre
- Centre Leon BerardRecruiting
- Centre Antoine LacassagneRecruiting
- Gustave RoussyRecruiting
- Academ Zienkenhuis Bij De UniversityRecruiting
- University Medical Center GroningenRecruiting
- Maastro Clinic-Maastricht Radiation OncologyRecruiting
- Erasmus University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A (RT, procarbazine, lomustine, vincristine)
Arm B (RT, temozolomide)
Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity.