A Phase I Study of Antisense Bcl-2 Oligonucleotide (G3139) in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumors
I. To determine the maximum tolerated dose (MTD) of G3139 in combination with carboplatin
II. To determine the quantitative and qualitative nature of toxicities of G3139 with
carboplatin and paclitaxel.
III. To measure G3139 activity in peripheral blood lymphocytes by quantitating Bcl-2/Bax
expression and transcription, as well as T-cell functioning and signaling.
IV. To measure G3139 activity in tumor biopsy specimens by quantitating Bcl-2/Bax expression
V. To determine the pharmacokinetics of carboplatin, paclitaxel, and G3139, as well as
intratumoral G3139 levels.
VI. To screen various signal transduction pathways that may be affected by Bcl-2
down-regulation in PBMC and tumor biopsy specimens in order to better understand the
mechanism of G3139 chemosensitization.
VII. To seek preliminary evidence of antitumor activity for the combination of G3139,
carboplatin, and paclitaxel.
OUTLINE: This is a dose-escalation study of oblimersen.
Patients receive oblimersen IV continuously on days 1-7 and paclitaxel IV over 3 hours and
carboplatin IV over 30 minutes on day 4. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
An additional cohort of 12-15 patients receives treatment as above with oblimersen at the
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) defined as the highest safely tolerated dose where at most 1 patient experiences a dose-limiting toxicities (DLT) and the next higher dose having at least 2 patients who experience DLT
University of Wisconsin Hospital and Clinics
United States: Food and Drug Administration
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