Clinical trial NCT00003909: Motexafin Gadolinium Plus Radiation Therapy in Treating Children With Newly Diagnosed Brain Stem Glioma
Official title: A Phase I Study of Motexafin Gadolinium (Xcytrin, NSC 695238) and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Untreated Childhood Brain Stem Glioma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 24
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as motexafin gadolinium may make the tumor cells more sensitive to radiation therapy. Phase I trial to study the effectiveness of motexafin gadolinium plus radiation therapy in treating children who have newly diagnosed brain stem glioma

Detailed description: OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and schedule of motexafin gadolinium administered prior to radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma.

II. Determine the toxic effects of this drug given at the MTD in these patients.

III. Determine the intratumor and brain distribution of this drug by magnetic resonance imaging (MRI) in these patients.

OUTLINE: This is a dose-escalation study of motexafin gadolinium.

Approximately 2-5 hours before radiotherapy, patients receive motexafin gadolinium IV over 5 minutes. Patients undergo radiotherapy 5 days a week for 6 weeks.

Cohorts of 3-6 patients receive escalating doses of motexafin gadolinium until the MTD is determined. The first cohort receives motexafin gadolinium 5 days a week for 3 weeks; the second cohort receives motexafin gadolinium 3 days a week for 6 weeks; and subsequent cohorts receive motexafin gadolinium 5 days a week for 6 weeks. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for up to 3 years.

PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for this study within 2 years.

Eligibility criteria: Inclusion Criteria:

* Clinically and radiographically (MRI) proven newly diagnosed diffuse intrinsic brainstem glioma

  * Greater than 50% intra-axial involvement of the pons, pons and medulla, pons and midbrain, or entire brainstem
  * Contiguous involvement of the thalamus or upper cervical cord allowed
* Performance status - ECOG 0-2
* More than 2 months
* Absolute neutrophil count at least 1,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10.0 g/dL (transfusion allowed)
* No glucose 6 phosphate dehydrogenase deficiency
* Bilirubin no greater than 1.5 times normal
* SGOT or SGPT less than 1.5 times normal
* Creatinine no greater than 1.5 times normal
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No concurrent immunomodulating agents
* No other concurrent chemotherapy
* Concurrent corticosteroid therapy allowed for increased intracranial pressure only
* No prior cranial radiotherapy
* No prior motexafin gadolinium
* No other concurrent experimental agents

Primary outcomes:
measure: MTD defined as the dose at which fewer than one-third of patients experience DLT assessed using CTC version 2.0
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
Study officials:
affiliation: Children's Oncology Group
name: Minesh Mehta
role: PRINCIPAL_INVESTIGATOR
References: