A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis

Javier Rodriguez, Eduardo Castañón, Jose Luis Perez-Gracia, Inmaculada Rodriguez, Antonio Viudez, Carlos Alfaro, Carmen Oñate, Guiomar Perez, Fernando Rotellar, Susana Inogés, Ascensión López-Diaz de Cerio, Leyre Resano, Mariano Ponz-Sarvise, Maria E Rodriguez-Ruiz, Ana Chopitea, Ruth Vera, Ignacio Melero, Javier Rodriguez, Eduardo Castañón, Jose Luis Perez-Gracia, Inmaculada Rodriguez, Antonio Viudez, Carlos Alfaro, Carmen Oñate, Guiomar Perez, Fernando Rotellar, Susana Inogés, Ascensión López-Diaz de Cerio, Leyre Resano, Mariano Ponz-Sarvise, Maria E Rodriguez-Ruiz, Ana Chopitea, Ruth Vera, Ignacio Melero

Abstract

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival -DFS-) 25.26 months, 95% CI 8.74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32-18.88).

Keywords: Colon cancer; Dendritic cell; Randomized clinical trial; Relapse prevention; Vaccine.

Conflict of interest statement

Ethics approval and consent to participate

All patients provided informed consent approved as the clinical trial protocol by the CEIC of the local Government of Navarra (CEIC). The IMPD dossier and the clinical trial protocol were approved by Agencia Española del Medicamento y productos sanitarios (AEMPS). This was an investigator initiated clinical trial sponsored by UNAV and fulfills requirements by spanish law (Real Decreto 1090/2015).

Consent for publication

Informed consent included consent for publication and patients are coded and made anonym according to good clinical practices.

Competing interests

IM served as an advisor to BMS, Roche, AstraZeneca, Genmab, Alligator, Tusk, Bioncotech, Merck-Serono.

IM receives research grants from BMS, Roche and Alligator.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Clinical trial design and treatment generation scheme. a Graphical summary of patient accrual, randomization and treatment. b Schematic representation of production of dendritic-cell vaccines loaded with autologous tumor lysate in patients undergoing complete surgical resection of colon cancer liver metastasis
Fig. 2
Fig. 2
Disease-Free survival curves. Kaplan-Meier curves represent disease-free survival of vaccination versus observation arms. Ticks in the curve represent censored data. Recurrences were documented by CT-Scan and number of subjects at risk are in the table below the graphs. Probability of the difference calculated by log-rank test is given together with the estimation of median DFS of both arms

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