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

Sponsor:	Children's Hospital Los Angeles
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00392886

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 III

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:

MedlinePlus related topics: Bone Marrow Transplantation Brain Cancer Cancer Childhood Brain Tumors

Drug Information available for: Cyclophosphamide Thiotepa Vincristine Methotrexate Cisplatin Etoposide Carboplatin Temozolomide Etoposide phosphate Vincristine sulfate

U.S. FDA Resources

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.

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

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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:	October 20, 2010
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
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 09, 2012