Pyrazoloacridine Plus Carboplatin in Treating Patients With Recurrent Glioma

Phase I/II Trial of Pyrazoloacridine and Carboplatin in Patients With Recurrent Glioma

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: carboplatin; Drug: pyrazoloacridine

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5404
      • CCOP - Scottsdale Oncology Program
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Des Moines, Iowa, United States, 50309-1016
      • CCOP - Iowa Oncology Research Association
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Hematology-Oncology
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Health Plaza
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
  • North Dakota
    • Bismarck, North Dakota, United States, 58501-5505
      • Medcenter One Health System
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
  • Ohio
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • CCOP - Geisinger Clinic and Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57709
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • CCOP - Sioux Community Cancer Consortium
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • CCOP - St. Vincent Hospital Cancer Center, Green Bay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: carboplatin; Drug: pyrazoloacridine
Experimental: 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.	Drug: carboplatin; Drug: pyrazoloacridine
Experimental: Arm III; Patients receive the same treatment as given in studies 1 and 2 without dose escalation.	Drug: carboplatin; Drug: pyrazoloacridine

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2000
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 3, 2013
• Last Update Submitted That Met QC Criteria: May 31, 2013
• Last Verified: September 1, 2003

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult oligodendroglioma; adult mixed glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Antineoplastic Agents; Carboplatin; NSC 366140
• Other Study ID Numbers: NCI-2012-01850; NCCTG-987254; CDR0000067963 (Registry Identifier: PDQ (Physician Data Query))