Clinical trial NCT00005976: Pyrazoloacridine Plus Carboplatin in Treating Patients With Recurrent Glioma
Official title: Phase I/II Trial of Pyrazoloacridine and Carboplatin in Patients With Recurrent Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Health Plaza
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Bismarck
country: United States
facility: Medcenter One Health System
state: North Dakota
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Cancer Center
state: North Dakota
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Mayo Clinic
name: Evanthia Galanis, MD
role: STUDY_CHAIR
References:
citation: 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.