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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00392886
First received: October 25, 2006
Last updated: December 17, 2013
Last verified: October 2010
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
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
Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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]

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to tumor progression, disease recurrence, or death of any cause [ Designated as safety issue: No ]
  • Event-free survival at 2 years [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response to induction as assessed by one-time tumor measurements at baseline and after completion of induction chemotherapy [ Designated as safety issue: No ]
  • Time to death [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: March 2004
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen C
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
Given IV
Drug: temozolomide
Given orally
Drug: thiotepa
Given IV
Drug: vincristine sulfate
Given IV
Procedure: autologous bone marrow transplantation
Given on day 0
Procedure: autologous hematopoietic stem cell transplantation
Given on day 0
Procedure: peripheral blood stem cell transplantation
Given on day 0
Radiation: radiation therapy
Some patients undergo radiation therapy once daily, 5 days a week for 4-6 weeks.
Experimental: Regimen D2
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
Given IV
Drug: cisplatin
Given IV
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV and orally
Drug: methotrexate
Given IV
Drug: temozolomide
Given orally
Drug: thiotepa
Given IV
Drug: vincristine sulfate
Given IV
Procedure: autologous bone marrow transplantation
Given on day 0
Procedure: autologous hematopoietic stem cell transplantation
Given on day 0
Procedure: peripheral blood stem cell transplantation
Given on day 0
Radiation: radiation therapy
Some patients undergo radiation therapy once daily, 5 days a week for 4-6 weeks.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00392886

  Show 37 Study Locations
Sponsors and Collaborators
Children's Hospital Los Angeles
Investigators
Study Chair: Jonathan L. Finlay, MB, ChB Children's Hospital Los Angeles
Investigator: Girish Dhall, MD Children's Hospital Los Angeles
Investigator: Kelley Haley, RN, BSN Children's Hospital Los Angeles
  More Information

Additional Information:
No publications provided

Responsible Party: Jonathan L. Finlay, Childrens Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT00392886     History of Changes
Other Study ID Numbers: CDR0000503990, CHLA-HEAD-START-III, CHLA-HSIII, CHLA-2004-020, CHLA-04.020, UMN-MT2004-06
Study First Received: October 25, 2006
Last Updated: December 17, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Etoposide phosphate
Temozolomide
Cisplatin
Cyclophosphamide
Etoposide
Methotrexate
Thiotepa
Vincristine
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on August 28, 2014