Abstract
Purpose: This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Patients and methods: Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m 2. Pharmacokinetic studies were performed in patients at all dose levels. Result: Twentyeight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m 2. One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m 2, and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m 2. Six patients were treated at the 18 mg/m 2 dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t1/2) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m 2 was 2,768 ng•h/ mL. Conclusion: A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m 2 may be a tolerable dose of TTI-237.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 266-272 |
| Number of pages | 7 |
| Journal | Investigational New Drugs |
| Volume | 30 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 1 2012 |
| Externally published | Yes |
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Keywords
- Anti-tubulin drugs
- Phase I study
- TTI-237
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Oncology
Cite this
A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors. / Wang-Gillam, Andrea; Arnold, Susanne M.; Bukowski, Ronald M.; Rothenberg, Mace L.; Cooper, Wendy; Wang, Kenneth K.; Gauthier, Eric; Lockhart, Albert.
In: Investigational New Drugs, Vol. 30, No. 1, 01.02.2012, p. 266-272.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors
AU - Wang-Gillam, Andrea
AU - Arnold, Susanne M.
AU - Bukowski, Ronald M.
AU - Rothenberg, Mace L.
AU - Cooper, Wendy
AU - Wang, Kenneth K.
AU - Gauthier, Eric
AU - Lockhart, Albert
PY - 2012/2/1
Y1 - 2012/2/1
N2 - Purpose: This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Patients and methods: Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m 2. Pharmacokinetic studies were performed in patients at all dose levels. Result: Twentyeight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m 2. One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m 2, and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m 2. Six patients were treated at the 18 mg/m 2 dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t1/2) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m 2 was 2,768 ng•h/ mL. Conclusion: A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m 2 may be a tolerable dose of TTI-237.
AB - Purpose: This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Patients and methods: Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m 2. Pharmacokinetic studies were performed in patients at all dose levels. Result: Twentyeight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m 2. One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m 2, and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m 2. Six patients were treated at the 18 mg/m 2 dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t1/2) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m 2 was 2,768 ng•h/ mL. Conclusion: A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m 2 may be a tolerable dose of TTI-237.
KW - Anti-tubulin drugs
KW - Phase I study
KW - TTI-237
UR - http://www.scopus.com/inward/record.url?scp=84856528207&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856528207&partnerID=8YFLogxK
U2 - 10.1007/s10637-010-9506-3
DO - 10.1007/s10637-010-9506-3
M3 - Article
C2 - 20697774
AN - SCOPUS:84856528207
VL - 30
SP - 266
EP - 272
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 1
ER -