Randomised phase II trial of gemcitabine and nab-paclitaxel with necuparanib or placebo in untreated metastatic pancreas ductal adenocarcinoma
| Autor: | David P. Ryan, Eileen M. O'Reilly, Kenneth H. Yu, James M. Roach, Donald A. Richards, Spencer H. Shao, Julie Wolf, Tanios Bekaii-Saab, Diletta Barone, Keith T. Flaherty, Devalingam Mahalingam, Molly Rosano, Silva Krause |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Paclitaxel medicine.drug_class Low molecular weight heparin Placebo Deoxycytidine Gastroenterology Article 03 medical and health sciences Subcutaneous injection 0302 clinical medicine Double-Blind Method Albumins Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Data monitoring committee Aged Aged 80 and over business.industry Hazard ratio Middle Aged Prognosis Interim analysis Gemcitabine Confidence interval Pancreatic Neoplasms Survival Rate 030104 developmental biology Oncology 030220 oncology & carcinogenesis Female Heparitin Sulfate business Carcinoma Pancreatic Ductal Follow-Up Studies medicine.drug |
| Zdroj: | Eur J Cancer |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2020.03.005 |
| Popis: | Background Necuparanib, a rationally engineered low-molecular-weight heparin, combined with gemcitabine/nab-paclitaxel showed an encouraging safety and oncologic signal in a phase Ib trial. This randomised multicentre phase II trial evaluates the addition of necuparanib or placebo to gemcitabine/nab-paclitaxel in untreated metastatic pancreatic ductal adenocarcinoma (PDAC). Patients and methods Eligibility included 18 years, histologically or cytologically confirmed metastatic PDAC, measurable disease and Eastern Co-Operative Oncology Group performance status of 0–1. Patients were randomly assigned to necuparanib (5 mg/kg subcutaneous injection once daily) or placebo (subcutaneous injection once daily) and gemcitabine/nab-paclitaxel on days 1, 8 and 15 of 28-day cycles. The primary end-point was median overall survival (OS), and secondary end-points included median progression-free survival, response rates and safety. Results One-hundred ten patients were randomised, 62 to necuparanib arm and 58 to placebo arm. The futility boundary was crossed at a planned interim analysis, and the study was terminated by the Data Safety Monitoring Board. The median OS was 10.71 months (95% confidence interval [CI]: 7.95–11.96) for necuparanib arm and 9.99 months (95% CI: 7.85–12.85) for placebo arm (hazard ratio: 1.12, 95% CI: 0.66–1.89, P-value: 0.671). The necuparanib arm had a higher incidence of haematologic toxicity relative to placebo patients (83% and 70%). Conclusion The addition of necuparanib to standard of care treatment for advanced PDAC did not improve OS. Safety was acceptable. No further development of necuparanib is planned although targeting the coagulation cascade pathway remains relevant in PDAC. NCT01621243 |
| Databáze: | OpenAIRE |
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