An Open-Label Phase I Study of the Safety of Perifosine in Combination With Sunitinib Malate for Patients With Advanced Cancers
This study is a Phase I trial in two parts. In part 1, an MTD to the combination of
perifosine and sunitinib malate will be determined. In some previous trials with perifosine
and other biologic agents, doses determined in Phase I studies are not as well tolerated in
larger groups of patients when response is an endpoint. Thus in part 2, with the MTD as a
starting point, a group of patients will be accrued with the goal of ensuring that they will
be able to tolerate at least two courses of therapy, which would make them evaluable for
response in a Phase II study. As a secondary endpoint, the effects of the combination of
perifosine and sunitinib malate will be evaluated for response rate and time to progression.
The pharmacokinetics of the combination of the study drugs will be measured.
For the purposes of this study, one cycle of therapy will be defined as 6 weeks. Patients
will take one 50 mg tablet of perifosine one to three times a day and sunitinib malate once
a day for 4 out of 6 weeks. Patients may need anti-emetics and/or anti-diarrheals.
Patients will be evaluated for progression or response at 12-week intervals.
Patients who experience toxicity may continue on treatment with doses delayed or reduced.
All patients should continue therapy unless disease progression is documented on two
occasions at least four weeks apart.
Part 1 of this Phase I study will accrue from six to 24 patients depending on the number of
dose levels evaluated. Up to six patients will be treated at each dose level. A dose
limiting toxicity (DLT) will be defined as:
- Grade 3 or greater non-hematologic toxicity
- Grade 4 hematologic toxicity
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
every 6 weeks
United States: Food and Drug Administration