Combination Chemotherapy With or Without Etoposide Followed By an Autologous Stem Cell Transplant in Treating Young Patients With Previously Untreated Malignant Brain Tumors

NCT00392886 | Unknown Phase 3

• 6 other identifiers: CDR0000503990CHLA-HEAD-START-IIICHLA-HSIIICHLA-2004-020CHLA-04.020UMN-MT2004-06
• Study Type: interventional
• Target: 120
• Locations: 5 countries
• Sites: 37

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A bone marrow or peripheral stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed. PURPOSE: This phase III trial is studying how well giving combination chemotherapy with or without etoposide followed by an autologous stem cell transplant works in treating young patients with previously untreated malignant brain tumors.

Conditions

Brain and Central Nervous System Tumors

Keywords

untreated childhood medulloblastoma; untreated childhood supratentorial primitive neuroectodermal tumor; childhood infratentorial ependymoma; childhood supratentorial ependymoma; newly diagnosed childhood ependymoma; childhood high-grade cerebral astrocytoma; childhood oligodendroglioma; childhood atypical teratoid/rhabdoid tumor; childhood choroid plexus tumor; untreated childhood cerebellar astrocytoma; untreated childhood visual pathway and hypothalamic glioma; untreated childhood pineoblastoma

Outcome Measures

Primary Outcomes (3)

• Time to tumor progression, disease recurrence, or death of any cause

• Event-free survival at 2 years

• Toxicity

Secondary Outcomes (3)

• Response to induction as assessed by one-time tumor measurements at baseline and after completion of induction chemotherapy

• Time to death

• Overall survival

Study Arms (2)

Regimen C

EXPERIMENTAL

Patients receive induction therapy of vincristine IV on days 1, 8, and 15 of courses 1-3, oral temozolomide once daily on days 1-5, and carboplatin IV over 4 hours on days 1 and 2. Patients also receive G-CSF SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive consolidation therapy of carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours on days -5 to -3, undergo reinfusion of bone marrow or peripheral blood stem cells on day 0, and receive G-CSF SC beginning on day 1 and continuing until blood counts recover. Beginning within 6 weeks after transplantation, some patients undergo radiotherapy once daily 5 days a week for 4-6 weeks in the absence of disease progression or unacceptable toxicity and some patients undergo radiotherapy if there is evidence of tumor remaining after completion of induction chemotherapy.

Drug: carboplatin; Drug: temozolomide; Drug: thiotepa; Drug: vincristine sulfate; Procedure: autologous bone marrow transplantation; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

Regimen D2

EXPERIMENTAL

In courses 1, 3, and 5, patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 2 and 3, high-dose methotrexate IV over 4 hours on day 4, vincristine IV on days 1, 8, and 15 (in courses1 and 3), and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. In courses 2 and 4, patients receive oral temozolomide once daily on days 1-5, oral etoposide once daily on days 1-10, cyclophosphamide IV over 1 hour on days 11 and 12, vincristine IV on days 1, 8, and 15 (in course 2), and G-CSF SC beginning on day 13 and continuing until blood counts recover. Patients receive consolidation therapy as in regimen C in combination with etoposide IV over 3 hours on days -5 to -3 and undergo autologous bone marrow or peripheral blood stem cell transplantation, receive G-CSF, and undergo radiotherapy as in regimen C.

Drug: carboplatin; Drug: cisplatin; Drug: cyclophosphamide; Drug: etoposide; Drug: methotrexate; Drug: temozolomide; Drug: thiotepa; Drug: vincristine sulfate; Procedure: autologous bone marrow transplantation; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

Interventions

carboplatin DRUG

Given IV

Regimen C; Regimen D2

cisplatin DRUG

Given IV

Regimen D2

cyclophosphamide DRUG

Given IV

Regimen D2

etoposide DRUG

Given IV and orally

Regimen D2

methotrexate DRUG

Given IV

Regimen D2

temozolomide DRUG

Given orally

Regimen C; Regimen D2

thiotepa DRUG

Given IV

Regimen C; Regimen D2

vincristine sulfate DRUG

Given IV

Regimen C; Regimen D2

autologous bone marrow transplantation PROCEDURE

Given on day 0

Regimen C; Regimen D2

autologous hematopoietic stem cell transplantation PROCEDURE

Given on day 0

Regimen C; Regimen D2

peripheral blood stem cell transplantation PROCEDURE

Given on day 0

Regimen C; Regimen D2

radiation therapy RADIATION

Some patients undergo radiation therapy once daily, 5 days a week for 4-6 weeks.

Regimen C; Regimen D2

Eligibility Criteria

• Age: Up to 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

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 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 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead

Study Sites (37)

Phoenix Children's Hospital Outpatient Center

Phoenix, Arizona, 85016, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

Long Beach, California, 90806, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Mattel Children's Hospital at UCLA

Los Angeles, California, 90095, United States

Location

Children's Hospital and Research Center Oakland

Oakland, California, 94609, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207-8482, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

University of Chicago Comer Children's Hospital

Chicago, Illinois, 60637, United States

Location

Riley's Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, 46202-5225, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Tomorrows Children's Institute at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Schneider Children's Hospital

New Hyde Park, New York, 11040, United States

Location

NYU Cancer Institute at New York University Medical Center

New York, New York, 10016, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Toledo Children's Hospital

Toledo, Ohio, 43601, United States

Location

St. Vincent Mercy Medical Center

Toledo, Ohio, 43608, United States

Location

Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Christchurch Hospital

Christchurch, 1, New Zealand

Location

Wellington Children's Hospital

Wellington, 6002, New Zealand

Location

Swiss Pediatric Oncology Group Bern

Bern, CH 3010, Switzerland

Location

Universitaets Kinderklinik

Bern, CH-3010, Switzerland

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Oligodendroglioma; Rhabdoid Tumor; Choroid Plexus Neoplasms

Interventions

Carboplatin; Cisplatin; Cyclophosphamide; Etoposide; Methotrexate; Temozolomide; Thiotepa; Vincristine; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Triethylenephosphoramide; Aziridines; Azirines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Jonathan L. Finlay, MB, ChB

  Children's Hospital Los Angeles

  STUDY CHAIR

• Girish Dhall, MD

  Children's Hospital Los Angeles

• Kelley Haley, RN, BSN

  Children's Hospital Los Angeles

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: March 1, 2004
• Primary Completion: December 1, 2010
• Last Updated: December 18, 2013

Record last verified: 2010-10

Locations

CH (2); NZ (2); AU (1); US (29); CA (3)