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 bryostatin 1 plus gemcitabine in
treating patients who have advanced cancer that has not responded to previous treatment.
- Determine the maximum tolerated dose of gemcitabine when given concurrently with
bryostatin 1 to patients with advanced refractory cancer.
- Access the pattern of toxicity of this drug regimen in this patient population.
- Determine the objective response rate, duration of response, and overall survival in
patients treated with this drug regimen.
- Determine the influence of bryostatin 1 on the pharmacokinetics of gemcitabine.
OUTLINE: This is a dose escalation study.
Patients receive gemcitabine IV over 30 minutes, immediately followed by bryostatin 1 IV
over 24 hours, weekly for 3 weeks (days 1, 8, and 15). Treatment repeats every 28 days in
the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of gemcitabine and bryostatin 1 until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose limiting toxic effects.
PROJECTED ACCRUAL: Approximately 2-3 patients per month will be accrued for this study.
- Histologically or cytologically proven advanced cancer (except hematological cancers)
for which there is no standard therapy or have failed standard therapies
- Measurable or evaluable disease
- Clinically controlled brain metastases allowed
- 18 and over
- SWOG 0-2
- At least 3 months
- Hemoglobin at least 8.0 g/dL
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 times upper limit of normal (ULN) (elevated bilirubin
due to Gilbert's syndrome allowed if direct bilirubin normal)
- AST less than 2.5 times ULN
- Creatinine normal
- No active cardiac disease
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No concurrent bacterial infection requiring antibiotics
- No serious concurrent medical condition
PRIOR CONCURRENT THERAPY:
- No concurrent immunotherapy
- At least 3 weeks since systemic cytotoxic chemotherapy (including gemcitabine) and
- No other concurrent chemotherapy
- Prior hormonal therapy allowed
- No concurrent hormonal therapy (excluding contraceptives, appetite stimulants, or
- At least 3 weeks since radiotherapy to large areas of active bone marrow and
- No concurrent radiotherapy
- Recovered from prior major surgery
- No concurrent antiviral nucleosides
- At least 1 month since prior investigational agents
- No other concurrent experimental medications
Philip A. Philip, MD, PhD, FRCP
Barbara Ann Karmanos Cancer Institute