Gliadel Wafer and O6-Benzylguanine in Treating Patients With Recurrent Glioblastoma Multiforme

Recurrent Adult Brain Tumor Clinical Trial

Official title:

Phase II Trial of Gliadel Plus 06-Benzylguanine for Patients With Recurrent Glioblastoma Multiforme

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00362921
• Other study ID #: Pro00004127
• Secondary ID: DUMC-5515-06-1R2
• Status: Completed
• Phase: Phase 2
• First received: August 10, 2006
• Last updated: July 9, 2014
• Start date: April 2004
• Est. completion date: July 2008

Study information

• Verified date: February 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as Gliadel wafer and O6-benzylguanine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving Gliadel wafer together with O6-benzylguanine works in treating patients with recurrent glioblastoma multiforme.

Description:

OBJECTIVES:

• Define the activity of Gliadel® wafers in combination with a 5-day infusion of O6-benzylguanine in patients with recurrent glioblastoma multiforme.

• Define the toxicity of Gliadel® wafers in combination with 5-day infusion of O6-benzylguanine in patients with recurrent glioblastoma multiforme.

OUTLINE: This is an open-label study.

Patients undergo surgical resection of tumor followed by placement of Gliadel® wafers . Within 6 hours after completion of surgery, patients receive a 1 hour high dose infusion of O6-benzylguanine followed by a lower dose continuous infusion for 5 days. Every 48 hours a repeat infusion of the high dose over 1 hour will be administered for a total of 3 doses.

After completion of study treatment, patients are followed every 8 weeks.

PROJECTED ACCRUAL: A total of 50 patients should be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: July 2008
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

DISEASE CHARACTERISTICS-

• Histologically confirmed recurrent glioblastoma multiforme (including gliosarcoma) which can be confirmed, if not earlier, by intraoperative pathological diagnosis on frozen section

• Evidence of a unilateral, single focus of measurable Central Nervous System (CNS) neoplasm on contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) scan that is supratentorial and measures = 1.0 cm in diameter

PATIENT CHARACTERISTICS-

• Greater than or equal to 18 years old

• Life expectancy of greater than 12 weeks

• Karnofsky performance status greater than or equal to 60%

• Absolute neutrophil count = 1,000/millimeters (mm)³

• Platelet count = 100,000/mm³

• Total Serum Bilirubin < 2 times upper limit of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT) < 3 times ULN

• Blood urea nitrogen (BUN) < 1.5 times ULN

• Creatinine < 1.5 times ULN

• Negative pregnancy test

• Recovered from any effects of major surgery

• Patients or legal guardian must give written, informed consent.

PRIOR CONCURRENT THERAPY-

• At least 2 weeks since prior surgical resection (if conducted) and recovered, unless there is unequivocal evidence of tumor progression

• At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas), unless there is unequivocal evidence of tumor progression.. However, patients treated with chemotherapeutic agents such as etoposide who would normally be retreated after shorter intervals (eg, 21 days on, 7 days off schedule) may be treated at the usual starting time even if less than 4 weeks from the last prior dose of chemotherapy.

EXCLUSION CRITERIA:

• Patients who have not recovered from surgery

• Patients who are not neurologically stable for 2 weeks prior to study entry

• Patients who are poor medical risks because of non-malignant systemic disease as well as those with acute infection treated with intravenous antibiotics

• Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction)

• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention

• Known HIV positivity or AIDS-related illness

• Pregnant or nursing women

• Women of childbearing potential who are not using an effective method of contraception. Women of childbearing potential must have a negative serum pregnancy test 24 hours prior to administration of study drug and be practicing medically approved contraceptive precautions.

• Men who are not advised to use an effective method of contraception

• Patients taking immuno-suppressive agents other than prescribed corticosteroids

• Patients who have had prior treatment with Gliadel Wafers.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Neoplasms
• Glioblastoma
• Recurrent Adult Brain Tumor

Intervention

Drug:
• Gliadel wafers in combination with O6-benzylguanine

Locations

Country	Name	City	State
United States	Duke Comprehensive Cancer Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Quinn JA, Jiang SX, Carter J, Reardon DA, Desjardins A, Vredenburgh JJ, Rich JN, Gururangan S, Friedman AH, Bigner DD, Sampson JH, McLendon RE, Herndon JE 2nd, Threatt S, Friedman HS. Phase II trial of Gliadel plus O6-benzylguanine in adults with recurren — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-month overall survival		6 months	No
Secondary	One year overall survival		1 year	No
Secondary	2 year overall survival		2 years	No
Secondary	Median overall survival		2 years	No
Secondary	Toxicity prevalence		2 years	Yes