RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of XK469 in treating patients who have
advanced solid tumors.
- Determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase II
dose of XK469 in patients with advanced solid tumors.
- Determine the safety of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine, preliminarily, any anti-tumor activity of this drug in these patients.
- Determine the drug metabolism, drug interaction potential, molecular and cellular
predictors of efficacy and toxicity, and clinical confirmation of molecular responses
in patients treated with this drug.
OUTLINE: This is a dose-escalation study.
Patients receive XK469 IV over 20 minutes on days 1-5. Treatment repeats every 21 days for
at least 2 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of XK469 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of the first 6
patients experience dose-limiting toxicity.
Once the MTD is determined, up to 15 patients are treated at that dose. Patients in the
expanded MTD cohort also receive oral NovaSoy® soybean extract twice daily for the study
Patients are followed every 4 weeks.
PROJECTED ACCRUAL: Approximately 25-40 patients will be accrued for this study within 12-15
- Histologically or cytologically confirmed non-hematological cancer that is
unresponsive to available therapies or for which there is no known effective
- Measurable or evaluable disease
- Clinical or radiological evidence of disease required
- No active brain metastases
- 16 and over
- ECOG 0-2
- At least 3 months
- Absolute neutrophil count at least 2,000/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 mg/dL
- ALT and AST no greater than 2.5 times upper limit of normal
- Creatinine less than 1.5 mg/dL
- Ejection fraction at least 50%
- No significant arrhythmias
- No congestive heart failure
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No dementia or altered mental status
- No known HIV infection
- No active infection
- No other serious uncontrolled medical disorder that would preclude study
- No known allergies to soy products, rice flour, or gelatin (if receiving study
dietary soy supplementation)
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior immunotherapy
- No concurrent prophylactic colony-stimulating factors
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- Prior taxanes allowed
- No other concurrent chemotherapy
- No concurrent hormonal therapy except hormone replacement therapy or medication used
to maintain castrate status for patients with progressive hormone-refractory prostate
- At least 4 weeks since prior radiotherapy
- No prior radiotherapy to more than 25% of bone marrow-containing areas
- No concurrent radiotherapy
- Not specified
- At least 4 weeks since prior investigational agents
- No other concurrent experimental anticancer therapy