A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression Journal Article
| Authors: | Li, D.; Pant, S.; Ryan, D. P.; Laheru, D.; Bahary, N.; Dragovich, T.; Hosein, P. J.; Rolfe, L.; Saif, M. W.; Lavalle, J.; Yu, K. H.; Lowery, M. A.; Allen, A.; O'Reilly, E. M. |
| Article Title: | A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression |
| Abstract: | Background Nucleotide transporters such as human equilibrative nucleoside transporter-1 (hENT1) play a major role in transporting gemcitabine into cells. CO-1.01 (gemcitabine-5′-elaidate) is a novel cytotoxic agent consisting of a fatty acid derivative of gemcitabine, which is transported intracellularly independent of hENT1. CO-1.01 was postulated to have efficacy as a second-line treatment in gemcitabine-refractory pancreatic adenocarcinoma in patients with negative tumor hENT1 expression. Methods Eligibility criteria included patients with either a newly procured or archival biopsy tumor confirming the absence of hENT1 and either gemcitabine-refractory metastatic pancreas adenocarcinoma or with progression of disease following resection during or within 3 months of adjuvant gemcitabine therapy. Patients were treated with intravenous infusion of CO-1.01 dosed at 1250 mg/m2 on Days 1, 8, and 15 of a 4-week cycle. The primary end point was disease control rate (DCR). Results Nineteen patients were enrolled of which 18 patients were evaluable for efficacy assessment. Thirteen patients (68%) had liver metastases, 6 (32%) had lymph node metastases, and 10 (53%) had lung metastases. Two of 18 patients (11%) achieved disease control. The median survival time was 4.3 (95% CI 2.1-8.1) months. All patients experienced at least one treatment-related adverse event with the majority of events being mild or moderate. Conclusion This study did not meet its primary endpoint and no efficacy signal was identified for CO-1.01 in treating progressive metastatic pancreas adenocarcinoma. |
| Keywords: | adult; cancer chemotherapy; cancer survival; clinical article; controlled study; human tissue; aged; cancer surgery; overall survival; fatigue; neutropenia; ascites; cancer growth; drug dose reduction; drug efficacy; drug safety; drug withdrawal; monotherapy; gemcitabine; adjuvant therapy; cancer adjuvant therapy; cancer patient; pancreas resection; outcome assessment; lymph node metastasis; cancer grading; cancer immunotherapy; progression free survival; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; gene expression; anemia; blood toxicity; leukopenia; thrombocytopenia; vomiting; deep vein thrombosis; patient assessment; cancer mortality; abdominal pain; asthenia; backache; drug fever; dyspnea; hyperglycemia; lymphocytopenia; pneumonia; lung embolism; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; confusion; hypoalbuminemia; hyponatremia; hypotension; survival time; liver metastasis; lung metastasis; biomarker; multicenter study; patient safety; pancreas adenocarcinoma; sepsis; open study; cancer control; drug dose increase; drug tolerance; hemolytic uremic syndrome; tachycardia; hypocalcemia; immunologic agent; equilibrative nucleoside transporter 1; cholangitis; spine fracture; human; male; female; article; co-1.01; disease-control rate; gemcitabine-refractory; hent1; gemcitabine elaidate |
| Journal Title: | Pancreatology |
| Volume: | 14 |
| Issue: | 5 |
| ISSN: | 1424-3903 |
| Publisher: | Karger |
| Date Published: | 2014-09-01 |
| Start Page: | 398 |
| End Page: | 402 |
| Language: | English |
| DOI: | 10.1016/j.pan.2014.07.003 |
| PROVIDER: | scopus |
| PUBMED: | 25278310 |
| PMCID: | PMC4461049 |
| DOI/URL: | |
| Notes: | Export Date: 1 December 2014 -- Source: Scopus |
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