Ph I 5-day Temozolomide + O6-BG in Treatment of Pts w Recurrent / Progressive GBM

NCT00612989 | Completed Phase 1 DMC

• 2 other identifiers: Pro000040586788
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objectives To determine maxi tolerated dose of Temodar® in combo w O6-benzylguanine administered for 5 consecutive days in pts w progressive/recurrent GBM To characterize toxicity associated w Temodar® in combo w O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM To determine Neulasta®-supported MTD defined as the MTD of Temodar® in combo with O6-BG administered for 5 days while receiving Neulasta® once per treatment cycle between days 7 \& 14 in pts w progressive/recurrent GBM To obtain preliminary response rates of Temodar® in combo w O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM

Conditions

Glioblastoma; Gliosarcoma

Keywords

Glioblastoma; Gliosarcoma; GBM; Temodar; Temozolomide; O6-BG; O6-Benzylguanine; Recurrent GBM; Progressive GBM; Brain tumor; Malignant glioma; Neulasta; Pegfilgrastim

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity

  6 months

Secondary Outcomes (1)

• Progression-free survival

  6 months

Study Arms (3)

1

EXPERIMENTAL

Schedule 1

Drug: Temodar and O6-Benzylguanine

2

EXPERIMENTAL

Schedule 2

Drug: Temodar and O6-Benzylguanine

3

EXPERIMENTAL

Schedule 2, Neulasta-supported

Drug: Temodar and O6-Benzylguanine

Interventions

Temodar and O6-Benzylguanine DRUG

O6-BG 120mg/m2 administered intravenously over 1 hr followed by continuous infusion of O6-BG at 30 mg/m2/day for 5 consecutive days. Every 48 hrs repeat dose of 120 mg/m2 over 1 hr administered for total of 3 doses. Temodar administered orally, in fasting state within 60 minutes of end of 1st 1-hr infusion of O6-BG \& then every 24 hrs during continuous infusion of O6-BG. Temodar administered on day 1 of treatment cycle \& every 24 hrs thereafter for 5 days with treatment cycles repeated every 28 days. Pts must fast for minimum of 1 hr prior to administration of each dose of Temodar \& continue fasting 2 hrs after administration of each Temodar dose.

Also known as: Temodar, Temozolomide, O6-BG, O6-Benzylguanine, NSC637037, Neulasta, Pegfilgrastim

1; 2; 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pts have histologically proven supratentorial GBM
• Pts have recurrent/progressive MG. If pt received stereotactic radiosurgery / brachytherapy as part of their prior therapy, then histologic confirmation of recurrence/metabolic imaging consistent w recurrent tumor is recommended but not mandated
• There must be measurable disease on contrast-enhanced magnetic resonance imaging study / CT scan performed \<2wks of study drug administration
• Interval of \>12 wks between completion of XRT \& enrollment on protocol
• Interval of \>4 wks between prior chemo \& enrollment on protocol unless there is unequivocal evidence of tumor progression
• Interval of \>2 wks between prior surgical resection \& enrollment on protocol unless there is unequivocal evidence of tumor progression
• Age \>18 yrs
• KPS \>70 percent
• Following baseline study will be required \<1wk of study drug administration: serum creatinine \< 1.5 x ULN \& Hematologic Status
• Following baseline studies will be required \<1wk of study drug administration: absolute neutrophil count \>2000 cells/microliter; platelet count \>125,000 cells/microliter
• Following baseline studies will be required \<1 wk of study drug administration: serum SGOT \& total bilirubin \< 2.5 x ULN
• Signed informed consent, approved by IRB, will be obtained prior to initiating treatment
• Pts w Reproductive Potential: Pts must agree to practice effective birth control measures while on study \& for 2 months after completing therapy

You may not qualify if:

• Pregnant/breast feeding women/ women/men w reproductive potential not practicing adequate contraception. Therapy may be associated w potential toxicity to fetus/child that exceeds mini risks necessary to meet health needs of mother
• Prior treatment w O6-BG + Temozolomide in combo
• Active infection requiring intravenous antibiotics
• Known diagnosis of HIV infection
• Pts w history of another primary malignancy that is currently clinically significant/currently requires active intervention
• Pts unwilling/unable to comply w protocol due to serious medical/psychiatric condition
• Pts who have received investigational drugs \<2 wks prior to start on study drug/have not recovered from side effects of such therapy.

Sponsors & Collaborators

• Duke University: lead
• Schering-Plough: collaborator
• Keryx / AOI Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms; Glioma

Interventions

Temozolomide; O(6)-benzylguanine; pegfilgrastim

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David A. Reardon, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 12, 2008
• Study Start: February 1, 2005
• Primary Completion: August 1, 2007
• Study Completion: July 1, 2008
• Last Updated: July 16, 2014

Record last verified: 2009-01

Locations

US (1)