Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

NCT00052780 | Completed Phase 1

• 4 other identifiers: NCI-2012-03174CDR653709PBTC-005U01CA081457
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I trial to study the safety of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug.

Conditions

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Outcome Measures

Primary Outcomes (1)

• MTD of temozolomide

  28 days

Secondary Outcomes (6)

• Pharmacokinetic parameters

  Baseline and courses 1 and 3

• Acute toxicities

  4 weeks (course 1)

• Chronic toxicities

  Up to 30 days post-treatment

• Histological response

  Up to 5 years

• Duration of disease control

  Up to 5 years

Study Arms (1)

Treatment (temozolomide, O6-benzylguanine)

EXPERIMENTAL

See Detailed Description

Drug: O6-benzylguanine; Drug: temozolomide; Biological: filgrastim; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

O6-benzylguanine DRUG

Given IV

Also known as: BG

Treatment (temozolomide, O6-benzylguanine)

temozolomide DRUG

Given PO

Also known as: SCH 52365, Temodal, Temodar, TMZ

Treatment (temozolomide, O6-benzylguanine)

filgrastim BIOLOGICAL

Given SC or IV

Also known as: G-CSF, Neupogen

Treatment (temozolomide, O6-benzylguanine)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (temozolomide, O6-benzylguanine)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (temozolomide, O6-benzylguanine)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Recurrent or refractory pediatric brain tumors; a histopathologic diagnosis from either the initial presentation or at the time of recurrence is required for all but brain stem gliomas
• Karnofsky or Lansky ≥ 60%
• Life expectancy \> 8 weeks
• Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to study entry
• Chemotherapy: No more than 2 previous chemotherapy/biologic therapy regimens; evidence of recovery from prior chemotherapy/biologic therapy; no myelosuppressive chemotherapy within 3 weeks (6 weeks if a nitrosourea agent) of study entry; patients who have received temozolomide are eligible if they have not received the drug in the past 3 months and did not experience any non-hematopoietic Grade 3/4 toxicity with prior temozolomide therapy
• XRT: ≥ 3 months prior to study entry for craniospinal irradiation (≥ 18 Gy); ≥ 4 weeks for local radiation to primary tumor; and ≥ 2 weeks prior to study entry for focal irradiation to symptomatic metastatic sites
• Bone Marrow Transplant: ≥ 6 months prior to study entry
• Anti-convulsants: Patients will be eligible for this study even if they are receiving anti-convulsants
• Growth factors: Off all colony forming growth factor(s) \> 2 weeks prior to study entry (G-CSF, GM-CSF, Erythropoietin)
• Dexamethasone: Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
• ANC \> 1,000/μl
• Platelets \> 100,000/μl
• Hemoglobin \> 8g/dl
• Patients may have bone marrow involvement by disease; platelet and Hgb counts must be transfusion independent
• Creatinine ≤ 1.5 times institutional normal for age

You may not qualify if:

• Patients must not be receiving any other anticancer or experimental drug therapy
• Patients with a history of hypersensitivity to dacarbazine, temozolomide or polyethylene glycol are excluded

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Pediatric Brain Tumor Consortium

Memphis, Tennessee, 38105, United States

Location

MeSH Terms

Conditions

Choroid Plexus Neoplasms; Astrocytoma; Oligodendroglioma; Familial ependymoma; Medulloblastoma; Optic Nerve Glioma

Interventions

O(6)-benzylguanine; Temozolomide; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Cerebral Ventricle Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Amar Gajjar

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2003
• First Posted: January 27, 2003
• Study Start: October 1, 2002
• Primary Completion: November 1, 2007
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

US (1)