Abstract | PURPOSE: METHODS: A two-stage, single-arm Phase II trial was conducted in patients with previously treated metastatic PDA. RO4929097 was administered at a dose of 20 mg daily on days 1-3, 8-10 and 15-17 of 21-day cycles. The primary endpoint was survival at 6 months. Secondary endpoints included overall survival (OS), response rate, toxicities, pharmacokinetic and pharmacodynamic analyses. RESULTS: Eighteen patients were recruited, 17 in the first stage and one in the 2nd stage. It was decided to stop further enrollment after RO4929097 was discontinued by the sponsor and was no longer a development candidate. Three (25 %) of 12 evaluable patients achieved stable disease. The 6-month survival rate was 27.8 % (95 % CI 9.7-53.5). The median OS was 4.1 months (95 % CI 2.7-5.8 months) and median progression-free survival was 1.5 months (95 % CI 1.3-1.6 months). Pharmacokinetic properties of RO4929097 in patients (n = 5) with PDA was similar to that previously reported in other patient populations. There was a trend towards a decrease in HeyL (p = 0.08) gene expression in three patients following study drug administration. CONCLUSIONS:
RO4929097 was well-tolerated in patients with previously treated PDA. Development of RO4929097 has been discontinued, but development of other notch-targeting agents in pancreatic cancer is continuing.
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Authors | Ana De Jesus-Acosta, Daniel Laheru, Anirban Maitra, John Arcaroli, Michelle A Rudek, Arvind Dasari, Patrick J Blatchford, Kevin Quackenbush, Wells Messersmith |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 32
Issue 4
Pg. 739-45
(Aug 2014)
ISSN: 1573-0646 [Electronic] United States |
PMID | 24668033
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
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Chemical References |
- Antineoplastic Agents
- Benzazepines
- Enzyme Inhibitors
- Amyloid Precursor Protein Secretases
- 2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide
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Topics |
- Adenocarcinoma
(drug therapy, metabolism)
- Aged
- Aged, 80 and over
- Amyloid Precursor Protein Secretases
(antagonists & inhibitors, metabolism)
- Antineoplastic Agents
(pharmacokinetics, therapeutic use)
- Benzazepines
(pharmacokinetics, therapeutic use)
- Disease-Free Survival
- Enzyme Inhibitors
(therapeutic use)
- Female
- Humans
- Male
- Middle Aged
- Pancreatic Neoplasms
(drug therapy, metabolism)
- Survival Rate
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