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A randomized phase II study of PX-12, an inhibitor of thioredoxin in patients with advanced cancer of the pancreas following progression after a gemcitabine-containing combination
- Source :
- Cancer chemotherapy and pharmacology. 67(3)
- Publication Year :
- 2010
-
Abstract
- This study evaluated PX-12, a novel small molecule inhibitor of the proto-oncogene (Trx-1), in patients with previously treated advanced pancreatic cancer (APC).PX-12 (54 or 128 mg/m²) was administered by 3-hour IV infusion daily × 5 days every 21 days (n = 17). Patients were randomized to either 54 or 128 mg/m² and then stratified based on CA 19-9 level (≥ 1,000 vs.1,000 U/ml) and SUV values on PET scans (≥ 7.0 vs.7.0). The primary endpoint was based on a progression-free survival (PFS) at 4 months in ≥ 40% of patients, and required 40 patients in each arm. An amendment required elevated Trx-1 levels (18 ng/ml) as an entry criteria after the first 17 patients were accrued.Plasma Trx-1 levels were elevated in 3/28 (11%) patients screened for study. The grade of the expired metabolite odor was higher in the 128 mg/m² arm. Therapy was well tolerated, and Grade ≥ 3 adverse events were uncommon. The best response was stable disease in 2 patients. There was no consistent decrease in SUV, Trx-1 levels or CA 19-9 levels with therapy. No patients had a PFS of4 months. Median PFS and survival were 0.9 months (95% CI 0.5-1.2) and 3.2 months (95% CI 2.4-4.2), respectively.Due to the lack of significant antitumor activity and unexpectedly low baseline Trx-1 levels, the study was terminated early. PX-12 does not appear to be active in unselected patients with previously treated APC.
- Subjects :
- Adult
Male
Cancer Research
medicine.medical_specialty
Pancreatic disease
Survival
medicine.drug_class
Phases of clinical research
Antineoplastic Agents
Toxicology
Antimetabolite
Gastroenterology
Deoxycytidine
Proto-Oncogene Mas
Disease-Free Survival
Thioredoxins
Pancreatic cancer
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Pharmacology (medical)
Disulfides
Adverse effect
Infusions, Intravenous
Aged
Pharmacology
Aged, 80 and over
Dose-Response Relationship, Drug
business.industry
Imidazoles
Cancer
Middle Aged
medicine.disease
Gemcitabine
Pancreatic Neoplasms
Dose–response relationship
Endocrinology
Treatment Outcome
Oncology
Disease Progression
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 14320843
- Volume :
- 67
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cancer chemotherapy and pharmacology
- Accession number :
- edsair.doi.dedup.....2311814963f5c4f270572ab46ae1408d