RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of paclitaxel and GEM 231 in treating
patients who have recurrent or refractory solid tumors.
OBJECTIVES: I. Determine the safety and maximum tolerated dose of GEM 231 and paclitaxel in
patients with recurrent or refractory solid tumors. II. Determine any preliminary antitumor
activity of this regimen in these patients.
OUTLINE: This is a dose escalation study of GEM 231. Patients receive paclitaxel IV over 3
hours on day 1, immediately followed by GEM 231 over 2 hours on days 1, 4, 8, 11, 15, and
18. Treatment continues every 3 weeks in the absence of disease progression or unacceptable
toxicity. Cohorts of 3-6 patients are treated with one of two doses of paclitaxel and
escalating doses of GEM 231 until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose at which no more than 2 of 6 patients experience dose limiting toxicity.
Patients are followed monthly for 3 months.
PROJECTED ACCRUAL: A maximum of 1 patient will be accrued per week for this study until the
maximum tolerated dose is reached.
DISEASE CHARACTERISTICS: Histologically confirmed advanced solid tumor that is refractory
to standard therapy or for which no standard therapy exists Measurable or evaluable
disease No CNS metastases that are untreated, associated with seizures, or require
intravenous medication and/or hospitalization
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-2 Life expectancy: Not
specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at
least 100,000/mm3 Hemoglobin at least 8.5 g/dL Hepatic: Bilirubin no greater than upper
limit of normal (ULN), except with Gilbert's syndrome (no greater than 1.5 times ULN if
liver metastases present) PT and aPTT normal SGOT or SGPT less than 3 times ULN (no
greater than 5 times ULN if liver metastases present) Renal: Creatinine less than 1.25
times ULN No renal tubular dysfunction (i.e., at least 2+ proteinuria within the past 2
weeks) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use
effective contraception for 1 month prior to, during, and 3 months after study No other
serious medical condition that would prevent compliance No serious infection No known
hypersensitivity to paclitaxel or other drugs formulated in Cremophor or any
oligodeoxynucleotides Adequate venous access No psychological or geographical condition
that would prevent compliance
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior transfusion Prior
biologic therapy allowed and recovered No concurrent biologic therapy Chemotherapy: Prior
chemotherapy allowed and recovered No other concurrent chemotherapy Endocrine therapy:
Prior hormonal therapy allowed and recovered Concurrent palliative hormonal therapy
allowed Radiotherapy: Prior radiotherapy allowed and recovered No concurrent radiotherapy
(except palliative) Surgery: At least 2 weeks since prior major surgery with wound
complications Other: At least 2 weeks since prior investigational drugs No other
investigational drugs during or within 28 days of study No concurrent CYP-3A metabolism