RATIONALE: Perifosine may stop the growth of tumor cells by stopping blood flow to the
PURPOSE: Phase I trial to study the effectiveness of perifosine in treating patients who
have advanced solid tumors.
- Determine the maximum tolerated dose (MTD) of perifosine on a loading dose/maintenance
dose schedule in patients with advanced solid tumors.
- Determine the qualitative and quantitative toxic effects of this drug in these
- Determine the pharmacokinetics of this drug in these patients.
- Investigate the relationship between pharmacokinetic parameters and toxicity of this
drug in these patients.
- Determine the recommended starting dose for phase II trials on this drug schedule in
- Evaluate the pharmacodynamic parameters on peripheral blood lymphocytes both before and
during drug administration in these patients.
- Determine any changes in the MTD with prolonged administration (3 months, 6 months) of
this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive a loading dose of oral perifosine 4 times a day for 4-8 doses followed by a
daily maintenance dose. Treatment continues every 28 days in the absence of unacceptable
toxicity or disease progression.
Cohorts of 3-6 patients receive escalating loading doses and maintenance doses of perifosine
until the maximum tolerated dose (MTD) of each 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 20-30 patients will be accrued for this study.
- Histologically confirmed locally unresectable or metastatic malignancy that is
- Refractory to further treatment with known forms of effective therapy
- No clinically active CNS metastasis
- 18 and over
- At least 12 weeks
- WBC at least 4,000/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- SGOT no greater than 2.5 times upper limit of normal
- Creatinine normal OR
- Creatinine clearance at least 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 6 months
after study participation
- Maintaining a reasonable state of nutrition consistent with weight maintenance
- No recent history of weight loss greater than 10% of current body weight
- No frequent vomiting/poor alimentation
- No other serious concurrent medical illness that would preclude study therapy
PRIOR CONCURRENT THERAPY:
- No concurrent immunotherapy
- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas)
- No other concurrent chemotherapy
- No concurrent hormonal therapy
- Patients who have progressive disease while being treated with LHRH agonists,
antiestrogens, or antitestosterones for at least 3 months may remain on these
agents if in their best interest
- At least 4 weeks since prior radiotherapy
- No concurrent radiotherapy
- See Disease Characteristics
- At least 21 days since prior major surgery