NCT04942626

Capecitabine-based Chemoradiotherapy in Combination With the IL-1 Receptor Antagonist Anakinra for Rectal Cancer Patients

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: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Goethe University · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Rectal Cancer

Interventions

Type	Name	Description
DRUG	Kineret 100 MG in 0.67 ML Prefilled Syringe	Anakinra 100 mg s.c. (Kineret) will be administered from day -10 (i.e. 10 days before initiation of RT) to the last day of RT.
DRUG	Capecitabine	Capecitabine will be administered using a 3+3 dose escalation design (500 mg/m2 bid, 650 mg/m2 bid and 825 mg/m2 bid po, respectively) from day 1 to day 40 of RT including weekends.
RADIATION	Radiotherapy	PTV: 1.8 Gy to 45 Gy (#28 fractions) to the primary tumor and pelvic lymph nodes; followed by a sequential boost of 1.8 Gy to 9 Gy (#5 fractions) to the gross tumor volume
PROCEDURE	Watch and Wait (cCR) or TME surgery (non-cCR)	Restaging to evaluate tumor response will be conducted 10 weeks after completion of CRT. For patients achieving a clinical complete response (cCR), a Watch and Wait (W\&W) option with close follow-up is scheduled. In case of non-cCR, immediate total mesorectal excision (TME) surgery is recommended. According to the current German S3-guidelines, adjuvant chemotherapy is optional.

Timeline

• Start date: 2021-08-20
• Primary completion: 2024-12-31
• Completion: 2024-12-31
• First posted: 2021-06-28
• Last updated: 2025-02-21

Locations

1 site across 1 country: Germany