Capecitabine-based Chemoradiotherapy in Combination With the IL-1 Receptor Antagonist Anakinra for Rectal Cancer Patients — ACO/ARO/AIO-21  

Rectal Cancer Clinical Trial

Official title: Capecitabine-based Chemoradiotherapy in Combination With the IL-1 Receptor Antagonist Anakinra for Rectal Cancer Patients. A Phase I Trial of the German Rectal Cancer Study Group

Status Active, not recruiting

Clinical Trial Summary

The ACO/ARO/AIO-21 investigator-driven, open-labeled, phase I drug re-purposing trial will assess whether the IL-1 receptor antagonist Anakinra can be safely combined with fluoropyrimidine-based chemoradiotherapy (CRT) in patients with rectal cancer.

Clinical Trial Description

Preoperative fluoropyrimidine-based chemoradiotherapy (CRT) and total mesorectal excision (TME) surgery 6-10 weeks thereafter, followed by optional adjuvant chemotherapy, has been the standard multimodal treatment for patients with UICC stage II and III rectal cancer during the last two decades. With this, pathological complete response rates (pCR) are in the range of 10%, 3 year-local failure rates in the range of 5%, distant recurrences occur in 25-30% of patients, and 3 years disease-free survival (DFS) amounts to 70%. More recently, total neoadjuvant treatment (TNT) with either 5x5 Gy or fluoropyrimidine-CRT, followed by consolidation chemotherapy with fluorouracil (or capecitabine) and oxaliplatin (FOLFOX/CAPOX), and TME, has significantly improved pCR and DFS compared to standard preoperative FU-CRT (+/- adjuvant chemotherapy) in recent phase 3 trials for patients with high-risk rectal cancer and has recently been accepted as standard treatment for this patient subgroup. In contrast, it remains unclear whether patients with intermediate risk rectal cancer benefit from TNT (currently under investigation in trials), whereas elderly and frail patients are not eligible for TNT and are rather be treated with 5x5 Gy or capecitabine-CRT alone. IL-1 is an inflammatory cytokine that plays a key role in tumor formation, progression and therapy resistance. Extensive studies of our group have showed that IL-1 mediates CRT resistance and disease progression in rectal cancer. Thus, blockade of IL-1 signaling using Anakinra constitutes an attractive option to significantly improve prognosis. The ACO/ARO/AIO-21 phase I drug re-purposing trial will assess whether the IL-1RA Anakinra can be safely combined with CRT in patients with rectal cancer. ;

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

• NCT number: NCT04942626
• Study type: Interventional
• Source: Goethe University
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 20, 2021
• Completion date: December 31, 2025