Motexafin Gadolinium and Radiation Therapy in Treating Young Patients With Pontine Glioma

A Phase II Study of Motexafin-Gadolinium (NSC 695238, IND #55583) and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood

This phase II trial is studying how well giving motexafin gadolinium together with radiation therapy works in treating young patients with pontine glioma. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as motexafin gadolinium, may make tumor cells more sensitive to radiation therapy. Giving motexafin gadolinium together with radiation therapy may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Untreated Childhood Brain Stem Glioma
• Intervention / Treatment: Drug: motexafin gadolinium; Radiation: 3-dimensional conformal radiation therapy

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate the effect of combining motexafin gadolinium with daily fractionated radiotherapy on 1-year event-free survival of pediatric patients with intrinsic pontine glioma (brain stem glioma).

SECONDARY OBJECTIVES:

I. Evaluate the effect of combining motexafin gadolinium with daily fractionated radiotherapy on 1-year overall survival of these patients.

II. Determine the toxicities of motexafin gadolinium in combination with radiotherapy in these patients.

OUTLINE: This is a multicenter study.

Patients receive motexafin gadolinium IV over 5-10 minutes once daily (prior to radiotherapy) 5 days a week for 6 weeks. Patients undergo focal cranial radiotherapy once daily 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 3 years and then periodically thereafter.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of intrinsic pontine glioma (brain stem glioma)

  • Clinical and radiographic (MRI) evidence of tumors that diffusely involve the brain stem (i.e., tumors that intrinsically [> 50% intra-axial] involve the pons or pons and medulla, pons and midbrain, or entire brain stem) allowed
  • Tumor may contiguously involve the thalamus or upper cervical cord
  • No more than 1 lesion/mass present at diagnosis
• Karnofsky performance status (PS) 60-100% (age > 16 years) OR Lansky PS 60-100% (age ≤ 16 years)
• Life expectancy ≥ 8 weeks
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³ (transfusion independent)
• Hemoglobin ≥ 10 g/dL (RBC transfusions allowed)
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine normal for age/gender (0.4-1.7 mg/dL)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT < 1.5 times ULN

• No known glucose-6-phosphate dehydrogenase (G6PD) deficiency

  • If family history suggestive of congenital hemolytic anemia, patient must be screened for G6PD with G6PD activity test prior to study entry
• No biliary obstruction
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior definitive therapy for this specific tumor
• No prior cranial radiotherapy
• Concurrent steroids and anticonvulsants allowed
• No concurrent proton therapy
• No concurrent intensity-modulated radiotherapy
• No concurrent anticancer chemotherapy
• No concurrent immunomodulating agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive motexafin gadolinium IV over 5-10 minutes once daily (prior to radiotherapy) 5 days a week for 6 weeks. Patients undergo focal cranial radiotherapy once daily 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: motexafin gadolinium; Given IV; Other Names: gadolinium texaphyrin; Gd (III) Texaphryin; Gd-Tex; PCI-0120; Xcytrin; Radiation: 3-dimensional conformal radiation therapy; Undergo focal cranial radiotherapy; Other Names: 3D-CRT; 3D conformal radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One Year Event-free Survival (EFS)	Percentage probability of being event-free at 1 year following enrollment.	One year after enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Percentage probability of being alive 1 year following enrollment.	One year after enrollment.
The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.	Occurrence of serious toxicity defined as any grade 4 hematologic toxicity that persists for more than 7 days or requires platelet transfusions for a time period exceeding 7 days; any grade 3 or 4 non-hematologic toxicity with the exception of grade 3 nausea or vomiting which can be controlled within 7 days; grade 3 skin reaction; grade 3 transaminitis.	One cycle of chemotherapy and radiation therapy; expected to be 42 days of treatment.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kristin Bradley, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: October 12, 2006
• First Submitted That Met QC Criteria: October 12, 2006
• First Posted (Estimate): October 13, 2006

Study Record Updates

• Last Update Posted (Actual): January 4, 2018
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Antineoplastic Agents; Photosensitizing Agents; Dermatologic Agents; Motexafin gadolinium
• Other Study ID Numbers: NCI-2012-01829 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA098543 (U.S. NIH Grant/Contract); CDR0000504107; COG-ACNS0222; ACNS0222 (Other Identifier: CTEP)