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

NCT ID: NCT00352313

Last Updated: 2012-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2008-01-31

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ATN-161

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

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.

Group Type: EXPERIMENTAL

ATN-161

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

Interventions

ATN-161

Given IV

Intervention Type: DRUG

carboplatin

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed intracranial malignant glioma

• Original low-grade glioma histology allowed provided there is subsequent histologic confirmation of malignant glioma
• Any of the following diagnoses:

• Glioblastoma multiforme
• Gliosarcoma
• Anaplastic astrocytoma
• Anaplastic oligodendroglioma
• Anaplastic mixed oligoastrocytoma
• Malignant astrocytoma not otherwise specified
• Recurrent disease

• Must have failed prior radiotherapy

• Must have confirmation of true progressive disease (rather than radiation necrosis) based upon either positron emission tomography or thallium scanning, MR spectroscopy, or surgical documentation of disease if radiographic recurrence is within the high-dose radiation field (for patients who underwent prior interstitial brachytherapy or stereotactic radiosurgery)
• Prior recent resection of recurrent or progressive tumors allowed if all of the following criteria are met:

• Recovered from prior surgery
• Evaluable disease after resection
• Unequivocal evidence of tumor progression by MRI

• Steroid dose must be stable for ≥ 5 days prior to MRI

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy > 8 weeks
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• AST < 2.5 times upper limit of normal (ULN)
• Bilirubin < 2.5 times ULN
• Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after completion of study treatment
• No significant medical illness that would preclude study treatment
• No history of other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless disease is in complete remission and off all therapy for ≥ 1 year
• No active infection or serious intercurrent medical illness
• No disease that will obscure toxicity or dangerously alter drug metabolism
• Able to undergo MRI scan and receive contrast agents for perfusion scanning

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• At least 28 days since prior cytotoxic therapy
• At least 14 days since prior vincristine
• At least 42 days since prior nitrosoureas
• At least 21 days since prior procarbazine
• At least 7 days since prior interferon, tamoxifen, thalidomide, isotretinoin, or other noncytotoxic agents (radiosensitizer does not count)
• At least 14 days since prior noncytotoxic investigational agents
• At least 42 days since prior radiotherapy
• No prior cisplatin, carboplatin, oxaliplatin, or platinum-containing analogue
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
• No other concurrent anticancer therapy (including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy)
• No other concurrent investigational drugs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Principal Investigators

Howard A. Fine, MD

Role: PRINCIPAL_INVESTIGATOR

NCI - Neuro-Oncology Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

06-C-0170

Identifier Type: -

Identifier Source: secondary_id

NCI-P6790

Identifier Type: -

Identifier Source: secondary_id

ATN-161-002

Identifier Type: -

Identifier Source: secondary_id

CDR0000487605

Identifier Type: -

Identifier Source: secondary_id

060170

Identifier Type: -

Identifier Source: org_study_id

NCT00340041

Identifier Type: -

Identifier Source: nct_alias