Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors
Central Nervous System Neoplasm, Pineoblastoma, Recurrent Medulloblastoma
About this trial
This is an interventional treatment trial for Central Nervous System Neoplasm
Eligibility Criteria
Inclusion Criteria:
- Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible
- Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence
- Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters
- All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment
- Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age)
- Patients must have a life expectancy of >= 8 weeks
- Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea)
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies
- External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry
- Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry
Study specific limitations on prior therapy:
- Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor
- Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry
Patients must have recovered from any surgical procedure before enrolling on this study:
- Patients with a major surgical procedure within 28 days prior to enrollment should be excluded
- Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded
- For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed
There should be no anticipation of need for major surgical procedures during the course of the study
Examples of major, intermediate, or minor surgical procedures:
- Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy
- Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy
- Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis
- Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy
- Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication
Concomitant medications restrictions:
- Growth factor(s): Must not have received within 7 days of entry onto this study
- Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days
- Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day
- Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days)
- Platelet count >= 100,000/uL (transfusion independent)
- Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions)
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows:
- =< 0.4 mg/dL (for patients aged 1 month to < 6 months)
- =< 0.5 mg/dL (for patients aged 6 months to < 1 year)
- =< 0.6 mg/dL (for patients aged 1 to < 2 years)
- =< 0.8 mg/dL (for patients aged 2 to < 6 years)
- =< 1 mg/dL (for patients aged 6 to < 10 years)
- =< 1.2 mg/dL (for patients aged 10 to < 13 years)
- =< 1.4 mg/dL (for female patients aged >= 13 years)
- =< 1.5 mg/dL (for male patients aged 13 to < 16 years)
- =< 1.7 mg/dL (for male patients aged >= 16 years)
- Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age
Central nervous system function defined as
- Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants
Adequate coagulation defined as
- International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal
Exclusion Criteria:
- Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study
- Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry
- Patients must not have a known bleeding diathesis or coagulopathy
- Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry
- Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history
- Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment
- Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible
- Patients must not have serious and inadequately controlled cardiac arrhythmia
- Female patients who are pregnant are not eligible for this study
- Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed
- Female patients of childbearing potential must have a negative pregnancy test
- Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
Sites / Locations
- Children's Hospital of Alabama
- University of Alabama at Birmingham Cancer Center
- Phoenix Childrens Hospital
- Arkansas Children's Hospital
- University of Arkansas for Medical Sciences
- Kaiser Permanente Downey Medical Center
- Loma Linda University Medical Center
- Miller Children's and Women's Hospital Long Beach
- Children's Hospital Los Angeles
- Cedars Sinai Medical Center
- Valley Children's Hospital
- Kaiser Permanente-Oakland
- Children's Hospital of Orange County
- Lucile Packard Children's Hospital Stanford University
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Rady Children's Hospital - San Diego
- UCSF Medical Center-Parnassus
- UCSF Medical Center-Mission Bay
- Connecticut Children's Medical Center
- Alfred I duPont Hospital for Children
- MedStar Georgetown University Hospital
- Children's National Medical Center
- Lee Memorial Health System
- Golisano Children's Hospital of Southwest Florida
- University of Florida Health Science Center - Gainesville
- Nemours Children's Clinic-Jacksonville
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- AdventHealth Orlando
- Nemours Children's Clinic - Orlando
- Orlando Health Cancer Institute
- Nemours Children's Hospital
- Nemours Children's Clinic - Pensacola
- Johns Hopkins All Children's Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Memorial Health University Medical Center
- University of Hawaii Cancer Center
- Kapiolani Medical Center for Women and Children
- Saint Luke's Cancer Institute - Boise
- Lurie Children's Hospital-Chicago
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Advocate Children's Hospital-Oak Lawn
- Saint Jude Midwest Affiliate
- Riley Hospital for Children
- Blank Children's Hospital
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Tulane University Health Sciences Center
- Children's Hospital New Orleans
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Dana-Farber Cancer Institute
- C S Mott Children's Hospital
- Wayne State University/Karmanos Cancer Institute
- Michigan State University Clinical Center
- Bronson Methodist Hospital
- 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
- Children's Mercy Hospitals and Clinics
- Cardinal Glennon Children's Medical Center
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- University Medical Center of Southern Nevada
- Sunrise Hospital and Medical Center
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Summerlin Hospital Medical Center
- Nevada Cancer Research Foundation NCORP
- Dartmouth Hitchcock Medical Center
- Hackensack University Medical Center
- Saint Barnabas Medical Center
- Morristown Medical Center
- Saint Peter's University Hospital
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Newark Beth Israel Medical Center
- Overlook Hospital
- University of New Mexico Cancer Center
- Albany Medical Center
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- The Steven and Alexandra Cohen Children's Medical Center of New York
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- University of Rochester
- State University of New York Upstate Medical University
- New York Medical College
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- 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
- University of Oklahoma Health Sciences Center
- Legacy Emanuel Children's Hospital
- Legacy Emanuel Hospital and Health Center
- Oregon Health and Science University
- Geisinger Medical Center
- Penn State Children's Hospital
- Children's Hospital of Philadelphia
- Children's Hospital of Pittsburgh of UPMC
- Rhode Island Hospital
- Medical University of South Carolina
- Prisma Health Richland Hospital
- BI-LO Charities Children's Cancer Center
- Greenville Cancer Treatment Center
- East Tennessee Childrens Hospital
- Vanderbilt University/Ingram Cancer Center
- 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
- Brooke Army Medical Center
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- Covenant Children's Hospital
- Methodist Children's Hospital of South Texas
- Primary Children's Hospital
- University of Vermont and State Agricultural College
- Children's Hospital of The King's Daughters
- Virginia Commonwealth University/Massey Cancer Center
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- University of Wisconsin Hospital and Clinics
- Marshfield Medical Center-Marshfield
- Children's Hospital of Wisconsin
- John Hunter Children's Hospital
- Sydney Children's Hospital
- The Children's Hospital at Westmead
- Royal Brisbane and Women's Hospital
- Royal Children's Hospital-Brisbane
- Queensland Children's Hospital
- Princess Margaret Hospital for Children
- Alberta Children's Hospital
- British Columbia Children's Hospital
- CancerCare Manitoba
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- Kingston Health Sciences Centre
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- Saskatoon Cancer Centre
- Centre Hospitalier Universitaire de Quebec
- Starship Children's Hospital
- Christchurch Hospital
- University Pediatric Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I (temozolomide, irinotecan hydrochloride)
Arm II (temozolomide, irinotecan hydrochloride, bevacizumab)
Patients receive temozolomide PO and irinotecan hydrochloride IV over 90 minutes on days 1-5.
Patients receive temozolomide PO and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.