Motexafin Gadolinium Plus Radiation Therapy in Treating Children With Newly Diagnosed Brain Stem Glioma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Untreated Childhood Brain Stem Glioma

Treatments: Radiation: radiation therapy; Drug: motexafin gadolinium; Other: pharmacological study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003909

COG-A09712

CDR0000067087 (Registry Identifier)

NCI-2012-01845

U01CA097452 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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.

Enrollment: 24 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Arm I

Experimental group

Description:

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

Treatment:

Other: pharmacological study

Drug: motexafin gadolinium

Radiation: radiation therapy