A Phase I Study of Intravenous CCI-779 in Combination With Bryostatin-1 in Solid Tumors (10038414)
Overview
- Phase
- Phase 1
- Intervention
- bryostatin 1
- Conditions
- Recurrent Melanoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- MTD of CCI-779 and Bryostatin-1 administered in combination, graded according to NCI Common Toxicity Criteria, Version 3.0
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This phase I trial is studying the side effects and best dose of temsirolimus when given together with bryostatin 1 in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as temsirolimus and bryostatin 1, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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 patients. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed solid tumor, including melanoma or renal cell carcinoma
- •Metastatic or unresectable disease
- •Must have evidence of residual, recurrent, or metastatic disease by radiography
- •Measurable disease
- •At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (CT scan, MRI, or x-ray) OR ≥ 10 mm by spiral CT scan
- •Must show clear evidence of disease progression within the lesion if the only site of measurable disease is within a previously irradiated volume
- •Standard curative or palliative measures do not exist OR are no longer effective
- •No history of or known brain metastases
- •Performance status - ECOG 0-1
- •At least 3 months
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (bryostatin, 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.
Intervention: bryostatin 1
Treatment (bryostatin, 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.
Intervention: temsirolimus
Outcomes
Primary Outcomes
MTD of CCI-779 and Bryostatin-1 administered in combination, graded according to NCI Common Toxicity Criteria, Version 3.0
Time Frame: 28 days
A dose-limiting toxicity is defined as a toxicity that is \>= grade 3 and drug-related.
Secondary Outcomes
- Changes in sum of RECIST measurements(Baseline up to 30 days after completion of study treatment)
- AKT activity, measured by immunohistochemistry (IHC), classified as none, weak, moderate, or strong(Up to 30 days after completion of study treatment)