Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific
Intervention: O6-benzylguanine (Drug); filgrastim (Drug); ifosfamide (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: University of Chicago Official(s) and/or principal investigator(s):
Sonali M. Smith, MD, Study Chair, Affiliation: University of Chicago
Summary
RATIONALE: Drugs used in chemotherapy, such as ifosfamide and O(6)-benzylguanine, work in
different ways to stop tumor cells from dividing so they stop growing or die. Combining
ifosfamide with O(6)-benzylguanine may kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects and best dose of
O(6)-benzylguanine when given together with ifosfamide and to see how well it works compared
to ifosfamide alone in treating patients with unresectable metastatic solid tumors.
Clinical Details
Official title: A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors
Study design: Treatment, Randomized, Open Label, Active Control
Detailed description:
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of O6-benzylguanine when administered with standard
high-dose ifosfamide in patients with unresectable, metastatic solid tumors.
- Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in
patients treated with this regimen.
- Determine the relationship between O6-benzylguanine dose and intra-individual
variability in the degree of myelosuppression in patients treated with this regimen.
- Determine the safety and toxicity of this regimen in these patients.
Secondary
- Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including
apoptosis and DNA damage, in patients treated with this regimen.
- Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in
patients treated with this regimen.
OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of
O6-benzylguanine.
- Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on
days 1-3.
- Course 2: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive high-dose ifosfamide as in course 1.
- Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on
day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over
72 hours on days 1-3.
Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a
continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience
dose-limiting toxicity.
- Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in
course 2, arm II) and high-dose ifosfamide as in course 2, arm II.
In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and
continuing until blood counts recover.
In all courses and in both arms, treatment repeats every 21 days in the absence of disease
progression or unacceptable toxicity.
PROJECTED ACCRUAL: A minimum of 32 patients (at least 2 in arm I and at least 24 in arm II)
will be accrued for this study within 12-15 months.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumor
- Unresectable, metastatic disease
- No primary tumors
- Eligible for high-dose ifosfamide-based therapy
- No known brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1 OR
- Karnofsky 70-100%
Life expectancy
- More than 12 weeks
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- AST and ALT ≤ 2. 5 times upper limit of normal
- Bilirubin normal
Renal
- Creatinine normal OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 weeks after study
participation
- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to O6-benzylguanine or other study agents
- No concurrent uncontrolled illness
- No active or ongoing infection
- No psychiatric illness or social situation that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or
sargramostim [GM-CSF])
- No prior hematopoietic stem cell transplantation
- No concurrent pegfilgrastim
- No concurrent immunotherapy
Chemotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered
- No other concurrent chemotherapy
Endocrine therapy
- No concurrent hormonal therapy
Radiotherapy
- More than 4 weeks since prior radiotherapy and recovered
- No concurrent therapeutic radiotherapy
Surgery
- Not specified
Other
- More than 4 weeks since prior anticancer therapy
- No more than 2 prior cytotoxic regimens
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer agents or therapies
- No other concurrent investigational agents
Locations and Contacts
University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: August 2004
Last updated: May 23, 2008
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