Determination of Optimal O6-Benzylguanine Dose to Achieve O6-Alkylguanine-DNA Alkyltransferase Depletion in Patients With Surgically Resectable Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- University of Chicago
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Determine minimal dose
Study Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed during surgery.
PURPOSE: Phase II trial to study the effectiveness of O6-benzylguanine followed by surgery in treating patients who have solid tumors that can be removed during surgery.
Detailed Description
OBJECTIVES: I. Determine the minimal O6-benzylguanine (O6-BG) dose required to deplete tumor activity to less than 10 fmol/mg protein at a specified time after administration in patients with surgically resectable solid tumors. II. Correlate tumor tissue AGT depletion with AGT depletion in peripheral blood mononuclear cells (PBMC) obtained at a specified time after O6-BG administration in these patients.
OUTLINE: This is a dose escalation study. Patients receive a single dose of O6-benzylguanine (O6-BG) IV over 1 hour at one of two dose levels. Patients undergo surgery 16-20 hours after administration of O6-BG. Up to 13 patients receive the lower dose level of O6-BG. If more than 3 patients have detectable AGT levels, additional patients receive the higher dose. The optimal biologic dose (OBD) is defined as the lowest dose level at which at least 11 of 13 patients have AGT activity less than 10 fmol/mg protein after O6-BG dosing. Patients are followed at 1 and 3 weeks post surgery.
PROJECTED ACCRUAL: A total of 13-26 patients will be accrued for this study over approximately 10 months.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A
06-benzylguanine (100mg/m2 16 hrs before anticipated tumor tissue removal)
Intervention: O6-benzylguanine (Drug)
Outcomes
Primary Outcomes
Determine minimal dose
Time Frame: 2 years
Determine minimal dose of 06-benzylguanine (06-BG) at which there is a depletion of tumor 06-BG DNA alkyltransferase activity to \<10 fmol/mg protein
Secondary Outcomes
No secondary outcomes reported