Randomized, Open-Label Study of the Biological Effects of BLP25 Liposome (L-BLP25) Immunotherapy in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy: Sprint Study Design
(2012) ESMO Congress 2012
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- Background Neoadjuvant chemoradiotherapy (NCR) followed by radical resection is the standard of care for patients with stage II-III rectal cancer. L-BLP25 (Stimuvax®) is an antigen-specific cancer immunotherapeutic agent targeting the mucin 1 (MUC1) antigen. It may act by inducing the proliferation of interferon (IFN)-γ secreting MUC1-specific CD4+ T-cells and the generation of cytotoxic T lymphocytes capable of killing MUC1-expressing tumours. In the SPRINT (Stimuvax® [L-BLP25] in Rectal cancer In Neoadjuvant chemoradioTherapy) study, we will evaluate immune responses to L-BLP25 in patients with rectal cancer undergoing NCR. Study design SPRINT is a phase II, multi-centre, open-label study in which patients (n = 24/arm) with resectable stage II-III rectal cancer are randomized to NCR (capecitabine 825 mg/m2 twice-daily for 5–7 d/wk; 45–52 Gy in fractions of 1.8/2 Gy for ≥5 wk) alone, NCR + L-BLP25, or NCR + L-BLP25 + cyclophosphamide (CPA). L-BLP25 is administered as 8 consecutive weekly subcutaneous doses (930 µg) beginning on the first day of NCR, followed by a final injection 7–9 d before surgery. CPA (300 mg/m2; maximum 600 mg) is given as a single intravenous infusion 3 d before the first L-BLP25 dose. Surgery will be performed 6–8 wk after the end of NCR. The primary objective is to assess L-BLP25-induced changes in immune response profile. The intra-tumoural response will be evaluated based on analysis of tumour-infiltrating lymphocytes (especially CD8+ and CD45RO+). Peripheral antigen-specific response will be assessed by measuring IFN-γ secretion by peripheral blood mononuclear cells (ELIspot assay) in response to MUC1 and carcinoembryonic antigen (CEA) as a test for ‘antigen spreading’. Secondary objectives include the assessment of additional immunological changes and correlation of intratumoural, peripheral and skin delayed-type hypersensitivity responses. Safety and pathological anti-tumour responses in resection specimens will be evaluated.
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Ruers, T. J. M., Aust, D., Van den Eynde, M., Folprecht, G., Carrasco, J., Fuchs, M., Smit, J. M., Victor, A., & Quaratino, S. (2012). Randomized, Open-Label Study of the Biological Effects of BLP25 Liposome (L-BLP25) Immunotherapy in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy: Sprint Study Design. Annals of Oncology, 23(9), ix211. https://doi.org/10.1016/s0923-7534(20)33092-1 (Original work published 2012)