Pyrazoloacridine Plus Carboplatin in Treating Patients With Recurrent Glioma

NCT ID: NCT00005976

Last Updated: 2013-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-05-31
• Study Completion Date: 2007-04-30

Brief Summary

Phase I/II trial to study the effectiveness of pyrazoloacridine plus carboplatin in treating patients who have recurrent glioma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of pyrazoloacridine plus carboplatin in patients with recurrent glioma.

II. Determine the toxic effects of this treatment regimen in these patients. III. Determine the safety of this treatment regimen at the recommended phase II dose in patients not receiving anticonvulsants.

IV. Determine the efficacy of this treatment regimen in these patients. V. Assess the pharmacokinetics and metabolism of pyrazoloacridine in these patients.

VI. Assess the response rate, time to progression, and time to death in patients treated with this regimen.

OUTLINE: This is a three-part, dose-escalation, multicenter study. Patients in study 3 are stratified according to concurrent anticonvulsants (yes vs no).

STUDY 1: (Study 1 closed as of 03/29/02) Patients receive carboplatin IV over 30 minutes and pyrazoloacridine IV over 3 hours on day 1. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of carboplatin and pyrazoloacridine 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.

STUDY 2: (Study 2 closed as of 03/29/02) Patients receive the same treatment as given in study 1. Dose escalation is performed as in study 1 to determine the MTD in patients not receiving concurrent anticonvulsants.

STUDY 3: Patients receive the same treatment as given in studies 1 and 2 without dose escalation.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL:

Study 1: A total of 3-21 patients will be accrued for this study within 6-20 months.

Study 2: A total of 3-12 patients will be accrued for this study within 3-18 months.

Study 3: A total of 12-37 patients will be accrued for this study within 15 months.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive carboplatin IV over 30 minutes and pyrazoloacridine IV over 3 hours on day 1. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of carboplatin and pyrazoloacridine 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.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

pyrazoloacridine

Intervention Type: DRUG

Arm II

Patients receive the same treatment as given in study 1. Dose escalation is performed as in study 1 to determine the MTD in patients not receiving concurrent anticonvulsants.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

pyrazoloacridine

Intervention Type: DRUG

Arm III

Patients receive the same treatment as given in studies 1 and 2 without dose escalation.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

pyrazoloacridine

Intervention Type: DRUG

Interventions

carboplatin

Intervention Type: DRUG

pyrazoloacridine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary brain glioma

• Diffuse astrocytoma
• Gliosarcoma
• Oligodendroglioma
• Oligoastrocytoma
• Progressive disease after radiotherapy
• Measurable or evaluable disease by MRI or CT

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• SGOT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No myocardial infarction within the past 6 months
• No congestive heart failure requiring therapy

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No other active malignancy
• No other concurrent severe disease

PRIOR CONCURRENT THERAPY:

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No more than 1 prior adjuvant chemotherapy regimen
• No prior polifeprosan 20 with carmustine implant (Gliadel wafer)
• Study 3 only:

• 1 prior chemotherapy regimen for recurrent disease allowed
• Prior nonplatinum-containing adjuvant chemotherapy allowed
• Prior platinum-containing adjuvant chemotherapy allowed if disease progressed at least 6 months after last treatment

Endocrine therapy:

• Non-increasing dose of corticosteroids for at least 1 week allowed

Radiotherapy:

• At least 12 weeks since prior radiotherapy
• No prior stereotactic radiosurgery or interstitial brachytherapy unless at least one lesion outside of irradiated area

Surgery:

• No surgical resection since prior radiotherapy or chemotherapy unless evidence of disease progression or lesion outside of treatment site

Other:

• Study 1 only: (Study 1 closed as of 03/29/02)

• Must be on anticonvulsants that can induce cytochrome P-450 (phenytoin, carbamazepine, barbiturates, or primidone)
• Study 2 only: (Study 2 closed as of 03/29/02)

• No concurrent anticonvulsants

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Evanthia Galanis, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

CCOP - Scottsdale Oncology Program

Scottsdale, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Siouxland Hematology-Oncology

Sioux City, Iowa, United States

CCOP - Wichita

Wichita, Kansas, United States

CCOP - Ochsner

New Orleans, Louisiana, United States

CCOP - Duluth

Duluth, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CentraCare Health Plaza

Saint Cloud, Minnesota, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Medcenter One Health System

Bismarck, North Dakota, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Altru Cancer Center

Grand Forks, North Dakota, United States

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Countries

United States; Canada

References

Galanis E, Buckner JC, Maurer MJ, Reid JM, Kuffel MJ, Ames MM, Scheithauer BW, Hammack JE, Pipoly G, Kuross SA. Phase I/II trial of pyrazoloacridine and carboplatin in patients with recurrent glioma: a North Central Cancer Treatment Group trial. Invest New Drugs. 2005 Oct;23(5):495-503. doi: 10.1007/s10637-005-2910-4.

Reference Type: RESULT

PMID: 16133802 (View on PubMed)

Other Identifiers

NCCTG-987254

Identifier Type: -

Identifier Source: secondary_id

CDR0000067963

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01850

Identifier Type: -

Identifier Source: org_study_id