Phase I trial to study the effectiveness of penclomedine in treating patients with malignant
solid tumors or lymphomas. Drugs used in chemotherapy use different ways to stop tumor cells
from dividing so they stop growing or die.
I. Determine the maximum tolerated dose (MTD) and Phase II dose of oral penclomedine in
patients with malignancies.
II. Determine the toxic effects of oral penclomedine in these patients. III. Determine the
pharmacokinetics of oral penclomedine in these patients. IV. Determine the bioavailability
of oral penclomedine in these patients.
Patients enrolled on the bioavailability portion of this study receive one dose of IV
penclomedine over 1 hour followed by 2 weeks of rest. At the end of two weeks, they receive
oral penclomedine for 5 days every 28 days. The starting dose is determined by a single
primary patient who has been administered oral penclomedine and observed for dose limiting
toxicity (DLT). [Bioavailability portion completed as of 3/98.] Those not on the
bioavailability portion of study start on a standard design dose escalating schedule in
which patients enroll in cohorts of 3. Patients are administered oral penclomedine daily for
5 days. This treatment repeats every 4 weeks. The MTD is defined as the dose immediately
below that at which 2 patients experience DLT. Treatment repeats for 6 courses or until
severe toxicity or tumor progression is observed.
- Histologically confirmed malignancy (solid tumor or lymphoma)
- No history of brain metastases
- Age: 18 and over
- Life expectancy: At least 12 weeks
- Performance status: ECOG 0-2
- WBC at least 4,000/mm3
- Absolute neutrophil count at least 1,500/mm3
- Platelet count at least 100,000/mm3
- Bilirubin less than 1.5 mg/dL
- Creatinine normal
- No history of seizure disorder Not pregnant or nursing
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas and mitomycin)
- At least 4 weeks since prior radiotherapy and recovered