Pyrazoloacridine Plus Carboplatin in Treating Patients With Recurrent Glioma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: carboplatin Drug: pyrazoloacridine	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/II Trial of Pyrazoloacridine and Carboplatin in Patients With Recurrent Glioma

Resource links provided by NLM:

Drug Information available for: Carboplatin

Genetic and Rare Diseases Information Center resources: Glioblastoma Gliosarcoma Glioma Oligodendroglioma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Brain Tumor, Adult Neuroepithelioma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):


Enrollment:	60
Study Start Date:	May 2000
Study Completion Date:	April 2007
Primary Completion Date:	December 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005976

Show 23 Study Locations

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Study Chair:	Evanthia Galanis, MD	Mayo Clinic

More Information

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.


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00005976 History of Changes
Other Study ID Numbers:	NCI-2012-01850 NCCTG-987254 CDR0000067963 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received:	July 5, 2000
Last Updated:	May 31, 2013

Keywords provided by National Cancer Institute (NCI):


recurrent adult brain tumor adult glioblastoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma	adult mixed glioma adult oligodendroglioma adult giant cell glioblastoma adult gliosarcoma

Additional relevant MeSH terms:


Glioma Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms	Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases NSC 366140 Carboplatin Antineoplastic Agents

ClinicalTrials.gov processed this record on June 27, 2017