A Phase I Study of Intravenous CCI-779 in Combination With Bryostatin-1 in Solid Tumors (10038414)
I. Determine the maximum tolerated dose and recommended phase II dose of temsirolimus when
given together with bryostatin 1 in patients with unresectable or metastatic solid tumors.
II. Determine the dose-limiting toxic effects of this regimen in these patients.
I. Correlate the extent and duration of inhibition of p70^S6kinase phosphorylation in
peripheral blood mononuclear cells with tumor growth or reduction in these patients.
II. Correlate the phosphorylation total and phospho-AKT and total and phospho ribosomal S6
protein (indicators of mTOR activation) with antitumor effects of this regimen in these
III. Correlate tumor expression of phospho-ERK1 and -ERK2 with antitumor effects of this
regimen in these patients.
IV. Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is a dose-escalation study of temsirolimus.
Patients receive bryostatin 1 IV over 1 hour on days 1, 8, 15, and 22 and temsirolimus IV
over 30 minutes once on days 8, 15, and 22 during course 1. On subsequent courses patients
receive bryostatin 1 and temsirolimus once on days 1, 8, and 15. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of CCI-779 and Bryostatin-1 administered in combination, graded according to NCI Common Toxicity Criteria, Version 3.0
A dose-limiting toxicity is defined as a toxicity that is >= grade 3 and drug-related.
Fox Chase Cancer Center
United States: Food and Drug Administration
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