ATN-161 and Carboplatin in Treating Patients With Recurrent Malignant Glioma

Phase 1

Completed

• Conditions: Brain and Central Nervous System Tumors
• Interventions: Drug: ATN-161; Drug: carboplatin

• Registration Number: NCT00352313
• Lead Sponsor: National Institutes of Health Clinical Center (CC)

Brief Summary

RATIONALE: ATN-161 may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ATN-161 together with carboplatin may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of ATN-161 when given together with carboplatin and to see how well they work in treating patients with recurrent malignant glioma.

Detailed Description

OBJECTIVES:

Primary

* Establish the safety of ATN-161 and carboplatin in patients with recurrent intracranial malignant glioma.

* Determine the maximum tolerated dose of ATN-161 when administered with carboplatin in these patients. (phase I)

* Determine the antitumor activity of ATN-161 when administered with carboplatin in these patients. (phase II)

Secondary

* Describe the effects of this regimen on potential biomarkers of activity, including functional imaging with brain perfusion scans and circulating endothelial progenitor cells.

* Obtain preliminary evidence of efficacy of this regimen in these patients. (phase I)

* Characterize the plasma concentrations of this regimen in these patients. (phase I)

OUTLINE: This is an open-label, phase I dose-escalation study of ATN-161 followed by a phase II study. Patients in the phase II portion of the study are stratified according to tumor type (glioblastoma multiforme vs anaplastic glioma).

* Phase I: Patients receive ATN-161 IV over 10 minutes 3 times weekly in weeks 1-6 and carboplatin IV over 20 minutes in week 3 during course 1. Beginning in course 2, patients receive carboplatin IV over 20 minutes in week 1 and ATN-161 IV over 10 minutes 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ATN-161 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity during the first 6 weeks of treatment.

* Phase II: Patients receive carboplatin IV in week 1 and ATN-161 IV, at the MTD determined in phase I, 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection at baseline and then periodically during phase I course 1 for pharmacokinetic and pharmacodynamic analysis and at baseline and then periodically during study for biomarker (e.g., circulating endothelial progenitor cells) correlative studies.

After completion of study treatment, patients are followed for 28 days.

PROJECTED ACCRUAL: A total of 82 patients will be accrued for this study.

Study Timeline

• Study Start: 2006-05
• Study First Submitted: 2006-07-13
• Study First Submitted QC: 2006-07-13
• Study First Posted: 2006-07-14
• Primary Completion: 2007-01
• Study Completion: 2008-01
• Status Verified: 2012-05
• Last Update Submitted: 2012-05-01
• Last Update Posted: 2012-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Phase I	ATN-161	Patients receive ATN-161 IV over 10 minutes 3 times weekly in weeks 1-6 and carboplatin IV over 20 minutes in week 3 during course 1. Beginning in course 2, patients receive carboplatin IV over 20 minutes in week 1 and ATN-161 IV over 10 minutes 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Phase I	carboplatin	Patients receive ATN-161 IV over 10 minutes 3 times weekly in weeks 1-6 and carboplatin IV over 20 minutes in week 3 during course 1. Beginning in course 2, patients receive carboplatin IV over 20 minutes in week 1 and ATN-161 IV over 10 minutes 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Phase II	carboplatin	Patients receive carboplatin IV in week 1 and ATN-161 IV, at the MTD determined in phase I, 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Phase II	ATN-161	Patients receive carboplatin IV in week 1 and ATN-161 IV, at the MTD determined in phase I, 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Response rate (phase I)
Overall survival
Safety
Maximum tolerated dose (phase I)
Progression-free survival at 6 months

Secondary Outcome Measures

Name	Time	Method
Efficacy
Response rate (phase II)

Trial Locations

Locations (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office; 🇺🇸 Bethesda, Maryland, United States