Abstract 509TiP
Background
Angiogenesis is associated with tumor progression, and antiangiogenic molecules have become a cornerstone in the treatment of advanced colorectal cancer (CRC). Regorafenib is a multi-kinase inhibitor targeting VEGFR1, 2, 3, TIE2, KIT, RET, RAF-1, BRAF, BRAFV600E, PDGFR, FGFR, and is an effective option in 20-25% of heavily pre-treated patients. Other therapies target the tumoral micro-environment, as metronomic chemotherapy (CT), with continuous low dose administration of a cytotoxic agent. This allows an anti-tumor effect, an anti-angiogenic activity, a stimulation of the immune system, and a better tolerance. A recent study performed in 66 metastatic CRC patients showed that aspirin and metronomic capecitabine administration was safe and induced promising clinical outcomes in a heavily pre-treated cohort (Giampieri et al, 2017). Following these clinico-biological observations, the REPROGRAM-01 study has been initiated.
Trial design
This is a French multi-center single-arm phase II study. Patients with metastatic CRC in progression after previous standard treatments, or who are not considered candidates for them, receive regorafenib with metronomic CT. Regorafenib is delivered according to the REDOS schedule (80 mg for week 1, 120 mg for week 2 and 160 mg for week 3 of the first cycle) and is administered 3 weeks out of 4, until progression. Metronomic CT is the association of capecitabine (625mg/m2 twice daily continuously for 6 months) with cyclophosphamide (50 mg daily for 6 months). Aspirin (75 mg once daily) is added until progression. The primary endpoint is overall response rate. Secondary endpoints are overall survival, progression-free survival, health related quality of life, toxicity, and the evaluation of exploratory biomarkers. A thorough monitoring of biological and radiological parameters will be undertaken to characterize the impact of this association on the reprogramming of immunological responses and on the stroma. Assuming a significance level of 5% and a power of 80%, a sample size of 49 patients is needed. The enrollment is ongoing,12 patients have already been recruited.
Clinical trial identification
2020-002344-23.
Editorial acknowledgement
Legal entity responsible for the study
Centre Hospitalier Régional et Universitaire Jean Minjoz, Besançon, France.
Funding
Partially supported by Bayer.
Disclosure
All authors have declared no conflicts of interest.