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Phase III Pilot Study of Induction Chemotherapy Followed by Consolidation Myeloablative Chemotherapy Comprising Thiotepa and Carboplatin With or Without Etoposide and Autologous Hematopoietic Stem Cell Rescue in Pediatric Patients With Previously Untreated Malignant Brain Tumors
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Registry Information
Alternate Title
Combination Chemotherapy With or Without Etoposide Followed By an Autologous Stem Cell Transplant in Treating Young Patients With Previously Untreated Malignant Brain Tumors
Basic Trial Information
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Phase
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Type
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Status
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Age
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Sponsor
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Protocol IDs
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Phase III
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Treatment
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Active
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Under 10 at diagnosis
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Other
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CHLA-HEAD-START-III CHLA-HSIII, CHLA-2004-020, CHLA-04.020, NCT00392886, UMN-MT2004-06
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Objectives Primary - Determine the 2-year event-free survival (EFS) and overall survival (OS) of pediatric patients with previously untreated nondisseminated medulloblastoma (< 4 years of age), disseminated medulloblastoma (< 10 years of age), or noncerebellar primitive neuroectodermal tumors (PNET) (disseminated or non-disseminated) treated with induction chemotherapy followed by consolidation with myeloablative chemotherapy and autologous hematopoietic stem cell rescue.
- Determine the toxicity of this regimen in these patients.
- Determine the mortality of patients treated with this regimen.
Secondary - Determine the complete and partial response rates after completion of induction chemotherapy in these patients stratified according to pathology (medulloblastoma vs noncerebellar PNET vs high-grade gliomas vs atypical teratoid/rhabdoid tumors vs choroid plexus carcinomas and atypical papillomas vs ependymomas).
- Describe the EFS and OS of these patients stratified according to additional diagnoses (atypical teratoid/rhabdoid tumors vs choroid plexus carcinomas and atypical choroid plexus papillomas vs ependymomas vs high-grade gliomas).
- Describe the time to progression and patterns of relapse in these patients stratified by diagnosis and radiotherapy received (< 6 years of age with evidence of no residual tumor pre-transplant and no post-transplant consolidation radiotherapy vs < 6 years of age with residual tumor present pre-transplant treated with post-transplant consolidation radiotherapy vs > 6 years of age treated with post-transplant consolidation radiotherapy).
- Determine the neuropsychometric function, endocrinologic function, and physical growth in these patients stratified according to radiotherapy received (none vs reduced-volume craniospinal radiotherapy vs focused local-field radiotherapy).
Entry Criteria Disease Characteristics:
- Histologically confirmed malignant brain tumor, including any of the following:
- Posterior fossa medulloblastoma/primitive neuroectodermal tumor (PNET)*
- All stages allowed
- Must be < 4 years of age at diagnosis unless there is evidence of postoperative residual tumor (> 1.5 cm² tumor area) or evidence of neuraxis or extraneural dissemination (high-stage)
- Medulloblastoma, cerebral neuroblastoma, and ependymoblastoma allowed
- Low-stage (standard-risk) medulloblastoma not allowed in patients > 4 years of age
- Ependymoma*
- All stages and locations allowed
- Cellular and anaplastic subtypes allowed (no myxopapillary ependymomas of the spinal cord)
- Must be < 36 months of age at diagnosis for posterior fossa tumor OR < 72 months of age for supratentorial tumor
- Evidence of neuraxis dissemination irrespective of primary site
- No cellular (low-grade) supratentorial ependymomas at any age with complete resection of parenchymally based (i.e., not periventricular) supratentorial tumors
- Brain stem tumor*
- All stages allowed irrespective of extent of resection
- No unbiopsied diffuse intrinsic pontine tumor
- Tumor pathologically confirmed to be either malignant glioma or PNET allowed
- High-grade glioma**
- Primary atypical teratoid/rhabdoid tumor of the CNS*
- Choroid plexus carcinoma or atypical choroid plexus papilloma*
- All stages and locations allowed
- Anaplastic astrocytoma**
- Glioblastoma multiforme**
- Anaplastic oligodendroglioma**
- Anaplastic ganglioglioma**
- Other anaplastic mixed gliomas**
- Small-cell glioblastoma**
- Giant-cell glioblastoma**
- Gliosarcoma**
- The following diagnoses or subtypes are not allowed:
- Choroid plexus papilloma
- Pineocytoma
- Low-grade mixed glioma
- Primary CNS germ cell tumor
- Primary CNS lymphoma
- Solid leukemic lesions (i.e., chloromas, granulocytic sarcomas)
- Pleomorphic xanthoastrocytoma, low grade
- Desmoplastic ganglioglioma
- Low-grade astrocytoma
- Previously untreated disease
- Has undergone definitive surgery within the past 42 days
[Note: *Patients receive treatment according to regimen D2] [Note: **Patients receive treatment according to regimen C] Prior/Concurrent Therapy:
- See Disease Characteristics
- No prior radiotherapy or chemotherapy
- Prior corticosteroids allowed
- No concurrent corticosteroids for antiemesis only
- No concurrent brachytherapy or electron radiotherapy
- No concurrent dairy products or grapefruit juice with temozolomide administration
Patient Characteristics:
- Bilirubin < 1.5 mg/dL
- ALT and AST < 2.5 times upper limit of normal
- Creatinine clearance and/or glomerular filtration rate ≥ 60 mL/min
Expected Enrollment 120A total of 120 patients will be accrued for this study. Outcomes Primary Outcome(s)Time to tumor progression, disease recurrence, or death of any cause Event-free survival at 2 years Toxicity
Secondary Outcome(s)Response to induction as assessed by one-time tumor measurements at baseline and after completion of induction chemotherapy Time to death Overall survival
Outline This is a pilot study. Patients are stratified according to type of tumor (nonglial vs glial and diffuse pontine). - Regimen C (patients with glial tumors):
- Regimen D2 (patients with nonglial tumors):
Patients in both regimens undergo neuropsychological testing after induction chemotherapy but before consolidation chemotherapy and then at 18, 36, and 54 months after completion of study treatment. Neuropsychometric and neuroendocrine testing is performed before and after radiotherapy. Quality of life is also assessed periodically. After completion of study treatment, patients are followed periodically.
Trial Contact Information
Trial Lead Organizations Childrens Hospital Los Angeles | | | Jonathan Finlay, MB, ChB, Protocol chair | | | | Girish Dhall, MD, Protocol co-chair | | | | Kelley Haley, RN, BSN, Research coordinator | | | | Trial Sites
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U.S.A. |
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Arizona |
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Phoenix |
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| | | | Phoenix Children's Hospital Outpatient Center |
| | Michael Etzl, MD | |
| Email:
metzl@phoenixchildrens.com |
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California |
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Loma Linda |
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| | | Loma Linda University Cancer Institute at Loma Linda University Medical Center |
| | Clinical Trials Office - Loma Linda University Cancer Institute | |
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Long Beach |
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| | Jonathan Jaques Children's Cancer Center at Miller Children's Hospital |
| | Ramesh Patel, MD | |
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Los Angeles |
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| | Childrens Hospital Los Angeles |
| | Jonathan Finlay, MB, ChB | |
| Email:
jfinlay@chla.usc.edu |
| | Mattel Children's Hospital at UCLA |
| | Joseph Lasky, MD | |
| Email:
jlasky@mednet.ucla.edu |
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Oakland |
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| | Children's Hospital and Research Center Oakland |
| | Clinical Trial Office - Children's Hospital and Research Center Oakland | |
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Orange |
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| | Children's Hospital of Orange County |
| | Wei-Ping Shen, MD | |
| Email:
vshen@choc.org |
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Delaware |
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Wilmington |
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| | | Alfred I. duPont Hospital for Children |
| | Clinical Trials Office - Alfred I. duPont Hospital for Children | |
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Florida |
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Jacksonville |
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| | | Nemours Children's Clinic |
| | Michael Joyce, MD, PhD | |
| Email:
mjoyce@nemours.org |
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Illinois |
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Chicago |
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| | | Children's Memorial Hospital - Chicago |
| | Stewart Goldman, MD | |
| | University of Chicago Comer Children's Hospital |
| | Charles Rubin, MD | Ph: | 773-702-6808 | | 800-289-6333 |
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| Email:
crubin@uchicago.edu |
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Indiana |
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Indianapolis |
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| | | Riley's Children Cancer Center at Riley Hospital for Children |
| | Kamnesh Pradhan, MD | |
| Email:
pkamnesh@iupui.edu |
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Kentucky |
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Louisville |
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| | | Kosair Children's Hospital |
| | Clinical Trials Office - Kosair Children's Hospital | |
| Email:
CancerResource@nortonhealthcare.org |
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Michigan |
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Grand Rapids |
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| | | Helen DeVos Children's Hospital at Spectrum Health |
| | Clinical Trials Office - Helen DeVos Children's Hospital | |
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Minnesota |
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Minneapolis |
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| | | Masonic Cancer Center at University of Minnesota |
| | Clinical Trials Office - Masonic Cancer Center at University of Minnesota | |
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Missouri |
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Kansas City |
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| | | Children's Mercy Hospital |
| | Richard Shore, MD | |
| Email:
rwshore@cmh.edu |
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New Jersey |
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Hackensack |
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| | | Tomorrows Children's Institute at Hackensack University Medical Center |
| | Steven Halpern, MD | |
| Email:
bdhalpern@aol.com |
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New York |
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Bronx |
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| | | Albert Einstein Cancer Center at Albert Einstein College of Medicine |
| | Clinical Trials Office - Albert Einstein Cancer Center at Albert Einstein College of Medicine | |
| Email:
aecc@aecom.yu.edu |
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New Hyde Park |
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| | Schneider Children's Hospital |
| | Mark Atlas, MD | |
| Email:
matlas@lij.edu |
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New York |
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| | Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center |
| | Clinical Trials Office - Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | |
| | NYU Cancer Institute at New York University Medical Center |
| | Sharon Gardner, MD | |
| Email:
sharon.gardner@med.nyu.edu |
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Syracuse |
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| | SUNY Upstate Medical University Hospital |
| | Clinical Trials Office - SUNY Upstate Medical University Hospital | |
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Ohio |
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Cleveland |
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| | | Cleveland Clinic Taussig Cancer Center |
| | Clinical Trials Office - Cleveland Clinic Taussig Cancer Center | |
| | Rainbow Babies and Children's Hospital |
| | Susan Wiersma, MD | |
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Columbus |
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| | Nationwide Children's Hospital |
| | Amanda Termuhlen, MD | |
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Toledo |
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| | St. Vincent Mercy Medical Center |
| | Rama Jasty, MD | |
| Email:
rjasty@med.umich.edu |
| | Toledo Children's Hospital |
| | Dagmar Stein, MD, PhD | |
| Email:
dagmar.stein@promedica.org |
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Pennsylvania |
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Hershey |
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| | | Penn State Children's Hospital |
| | Melanie Comito, MD | Ph: | 717-531-6012 | | 800-243-1455 |
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| Email:
mac36@psu.edu |
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Texas |
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Houston |
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| | | M. D. Anderson Cancer Center at University of Texas |
| | Clinical Trials Office - M. D. Anderson Cancer Center at the University of Texas | |
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Australia |
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Western Australia |
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Perth |
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| | | | Princess Margaret Hospital for Children |
| | David Baker, MD, MBBS, FRACP, FRCPA | |
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Canada |
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British Columbia |
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Vancouver |
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| | | | Children's & Women's Hospital of British Columbia |
| | Paul Rogers, MB, ChB, FRCPC, MBA, FRCP | |
| Email:
progers@cw.bc.ca |
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Manitoba |
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Winnipeg |
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| | | CancerCare Manitoba |
| | David Eisenstat, MD | |
| Email:
eisensta@cc.umanitoba.ca |
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Ontario |
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Toronto |
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| | | Hospital for Sick Children |
| | Annie Huang, MD | |
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New Zealand |
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Christchurch |
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| | | Christchurch Hospital |
| | Michael Sullivan, MD, PhD, FRACP | |
| Email:
micke.sullivan@otago..ac.nz |
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Wellington |
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| | Wellington Children's Hospital |
| | Elizabeth Hesketh, MD | |
| Email:
liz.hesketh@ccdhb.org.nz |
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Switzerland |
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Bern |
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| | | Swiss Pediatric Oncology Group Bern |
| | Andreas Hirt, MD | |
| Email:
andreas.hirt@insel.ch |
| | Universitaets Kinderklinik |
| | Andreas Hirt, MD | |
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Registry Information | | Official Title | | Dose Intensive Chemotherapy for Children Less Than Ten Years of Age Newly-Diagnosed with Malignant Brain Tumors: A Pilot Study of Two Alternative Intensive Induction Chemotherapy Regimens, Followed by Consolidation with Myeloablative Chemotherapy (Thiotepa and Carboplatin, With or Without Etoposide) and Autologous Stem Cell Rescue [HEAD START III] | | Trial Start Date | | 2004-03-22 | | Registered in ClinicalTrials.gov | | NCT00392886 | | Date Submitted to PDQ | | 2006-10-17 | | Information Last Verified | | 2008-08-12 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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