Phase I/Ib study of crenolanib with ramucirumab and paclitaxel as second-line therapy for advanced esophagogastric adenocarcinoma.
Cancer Chemother Pharmacol
; 89(2): 255-265, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-35066693
ABSTRACT
PURPOSE:
Paclitaxel plus ramucirumab is a standard second-line regimen for patients with advanced gastric adenocarcinoma, but clinical benefit remains modest. One potential resistance mechanism to VEGFR2 inhibition is activation of the PDGF/PDGFR pathway, which can be blocked by the selective inhibitor crenolanib. Therefore, we performed a phase I/Ib study of crenolanib in combination with paclitaxel/ramucirumab.METHODS:
Patients with metastatic esophagogastric adenocarcinoma refractory to first-line therapy received escalating doses of crenolanib [60 mg twice daily (BID) to 100 mg three times daily (TID)] in combination with paclitaxel 80 mg/m2 intravenously on days 1, 8 and 15 and ramucirumab 8 mg/kg intravenously on days 1 and 15 of a 28-day cycle. The primary objective was to determine the maximally tolerated dose (MTD) of crenolanib. Additional patients were enrolled in the dose expansion cohort to assess 6-month progression-free survival (PFS) at the MTD.RESULTS:
We enrolled 19 patients in the dose escalation phase and 8 patients in the dose expansion phase at the MTD of crenolanib 100 mg BID. Common grade 3/4 treatment-emergent adverse events included leukopenia (19%), anemia (11%) and neutropenia (11%). In the 14 patients treated at the MTD, 6-month PFS was 43% [95% confidence interval (CI) 23-78%] and the objective response rate (ORR) was 42% (95% CI 15-72%). The trial was terminated early due to withdrawal of crenolanib by the sponsor.CONCLUSIONS:
The addition of crenolanib to paclitaxel/ramucirumab is safe and well-tolerated at a dose level up to 100 mg BID. CLINICAL TRIAL REGISTRATION NCT03193918. June 19, 2017.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Neoplasias Esofágicas
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Adenocarcinoma
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Protocolos de Quimioterapia Combinada Antineoplásica
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos