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
Abstract
Purpose 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). Methods 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. 18 ng/ml) as an entry criteria after the first 17 patients were accrued. Results 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 of >4 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. Conclusions 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.
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A phase II trial of PX-12 in patients with advanced pancreatic cancer was terminated early due to lack of significant efficacy.
“However, a phase II trial of PX-12 in patients with advanced pancreatic cancer was terminated early due to lack of significant efficacy (Ramanathan et al., 2011).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Ramanathan et al., 2011
Clinical evaluation of PX-12 failed to demonstrate beneficial effects on VEGF suppression or tumor progression.
“clinical evaluation of PX-12 failed to demonstrate beneficial effects on VEGF suppression or tumor progression [359,360]”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [359]
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“However, a phase II trial of PX-12 in patients with advanced pancreatic cancer was terminated early due to lack of significant efficacy (Ramanathan et al., 2011).”
BackgroundTargeting the Thioredoxin System for Cancer Therapy
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Self-citationHIF inhibition: Current strategies and clinical challenges
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“However, clinical evaluation of PX-12 failed to demonstrate beneficial effects on VEGF suppression or tumor progression [359,360] and no active clinical trials are currently ongoing.”
- Authors
- Ramanathan, R. K., Abbruzzese, J., Dragovich, T., Kirkpatrick, L., Guillen, J. M., Baker, A. F., Pestano, L. A., Green, S., & Von Hoff, D. D.
- Affiliations
- Translational Genomics Research Institute (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Arizona (US)
- Corresponding author
- Ramanathan, Ramesh K.
- Venue
- Cancer Chemotherapy and Pharmacology
- Published
- 2010-05-12
- Volume
- 67
- Issue
- 3
- Pages
- 503-509
- ISSN
- 0344-5704 (ISSN-L)
- 1432-0843
- OpenAlex
- W2056660135
- Cited by
- 122
- References
- 0
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 3 · 2021: 8 · 2020: 12 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 13 · 2015: 10 · 2014: 5 · 2013: 1 · 2012: 10
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Chemotherapy and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R44CA075923, P01CA109552)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- PX-12, advanced pancreatic cancer, gemcitabine-refractory disease, progression-free survival, CA19-9, drug tolerability, anticancer activity
- MeSH terms
- Proto-Oncogene Mas, Gemcitabine, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Deoxycytidine, Disulfides, Dose-Response Relationship, Drug, Female, Humans, Imidazoles, Infusions, Intravenous, Male, Middle Aged, Pancreatic Neoplasms, Survival, Thioredoxins, Treatment Outcome, Disease Progression, Disease-Free Survival
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