| Autor: |
J. Lee, A. Dean, T. Price, K. Sjoquist, V. Gebski, J. Mumford, F. Day, S. Yip, K. Wilson, C. Jackson, S. Padinharakam, B. Lee, M. Burge, D. Siu, C. Karapetis, L. Chantrill, Z.W. Wong, R. Jennens, C. Lomma, A. Franscesconi, S. Ackland, J. Lynam, S. Wahlroos, J. So, M. Jameson, N. Tebbutt, S. Gill, D. Grimes, C. Steer, M. Harris |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
ESMO Gastrointestinal Oncology, Vol 1, Iss , Pp 3-8 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2949-8198 |
| DOI: |
10.1016/j.esmogo.2023.07.001 |
| Popis: |
Background: The dense stroma of pancreatic ductal adenocarcinoma (PDAC) is thought to impede tumour drug delivery. LSTA1, a novel cyclic tumour-penetrating peptide internalising arginylglycylaspartic acid, promotes tumour-specific drug delivery. In the phase Ib setting, LSTA1 3.2 mg/kg with gemcitabine and nab-paclitaxel showed a 92% disease control rate at 16 weeks and was well tolerated. Methods/design: This is a multicentre, phase II, double-blinded, placebo-controlled, randomised trial evaluating the activity and safety of LSTA1 in combination with gemcitabine and nab-paclitaxel in untreated advanced PDAC. Initially, participants were randomised 2 : 1 to receive gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2 and LSTA1 3.2 mg/kg or placebo. The trial design was updated in a protocol amendment (v4.0) to include a second placebo-controlled cohort which receives a second dose of LSTA1/placebo 4 h following chemotherapy. Treatment is administered on days 1, 8, and 15 of each 28-day cycle until progression (progressive disease). The sample size is 155 based on a clinically worthwhile increase in 6-month progression-free survival (PFS) of 16%-63% with 80% power and 95% confidence to exclude the null hypothesis. The recruitment period is 22 months and follow-up 18 months. Study endpoints are: (1) PFS; (2) objective response rate (RECIST 1.1), safety (Common Terminology Criteria for Adverse Events v5.0), overall survival, participant-reported outcomes; (3) predictive/prognostic biomarkers via archival tissue, and to assess whether a second dose of LSTA1 warrants further evaluation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
