A Phase I Pharmacokinetics and Pharmacodynamic Study of GTI2040 in Combination With Gemcitabine in Patients With Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Pharmacokinetics and Pharmacodynamic Study of GTI2040 in Combination With Gemcitabine in Patients With Solid Tumors
OBJECTIVES: Primary I. Determine the toxicity profile and maximum tolerated dose of GTI-2040
and gemcitabine in patients with metastatic or unresectable solid tumors.
Secondary I. Determine the pharmacokinetics and pharmacodynamics of this regimen in these
patients.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive GTI-2040 IV continuously on days 2-16 of course 1 and on days 1-16 of all
subsequent courses and gemcitabine IV over 30 minutes on days 1, 8, and 15 of course 1 and
on days 2, 9, and 16 of all subsequent courses. Courses repeat every 28 days in the absence
of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of GTI-2040 and gemcitabine until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is
determined, 10 additional patients are treated at that dose.
PROJECTED ACCRUAL: Approximately 18-40 patients will be accrued for this study within 6-20
months.
Inclusion Criteria:
- Histologically or cytologically confirmed solid tumor
- Metastatic or unresectable disease for which standard curative or palliative
measures do not exist or are no longer effective
- Measurable or evaluable disease
- No known active or progressive brain metastases or primary brain tumors
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- More than 12 weeks
- Hemoglobin > 9 g/dL
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN (5 times ULN if hepatic metastases are present)
- Creatinine ≤ 2.0 mg/dL
- Creatinine clearance ≥ 50 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior allergic reaction attributed to compounds of similar chemical or biological
composition to study drugs
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other condition (e.g., dementia or developmental delay) that would preclude giving
informed consent
- No other concurrent uncontrolled illness that would preclude study participation
- Prior biologic therapy allowed
- No concurrent biologic therapy
- No concurrent immunotherapy
- No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF)
- Prior gemcitabine allowed
- Prior investigational chemotherapy allowed
- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin, carmustine, or
nitrosoureas) and recovered
- No other concurrent chemotherapy
- Concurrent hormonal therapy (e.g., luteinizing hormone-releasing hormone agonists)
for prostate cancer is allowed
- At least 4 weeks since prior radiotherapy and recovered
- No prior radiotherapy to more than 25% of bone marrow
- No concurrent radiotherapy
- Recovered from prior surgery
- No other concurrent investigational therapy
- No other concurrent anticancer therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent long-term oral anticoagulation therapy (e.g., warfarin)
- Prophylactic warfarin to maintain central venous access patency allowed
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (MTD) of GTI-2040 and gemcitabine hydrochloride, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0
Outcome Time Frame:
Up to day 28
Safety Issue:
Yes
Principal Investigator
Chris Takimoto
Investigator Role:
Principal Investigator
Investigator Affiliation:
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02577
NCT ID:
NCT00078962
Start Date:
January 2004
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| Cancer Therapy and Research Center at The UT Health Science Center at San Antonio | San Antonio, Texas 78229 |
