NCT04719988

Anti-PD-1 and mDCF Followed by Chemoradiotherapy in Patients With Stage III Squamous Cell Anal Carcinoma.

Ezabenlimab (BI 754091) and mDCF (Docetaxel, Cisplatin and 5-fluorouracil) Followed by Chemoradiotherapy in Patients With Stage III Squamous Cell Anal Carcinoma. A Phase II Study

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Sponsor: Centre Hospitalier Universitaire de Besancon · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Squamous cell carcinoma of the anus (SCCA) is a rare cancer, however its incidence is increasing worldwide. SCCA is mostly induced by human papillomavirus (HPV) infections (high-risk types such as HPV-16 and -18) and HPV-related oncoproteins (E6 and E7) are expressed in more than 90% of cases. T stage and N stage are recognized prognostic factors for local and/or distant recurrence in SCCA patients treated by CRT. In fact, ≥T3 or ≥N1 anal cancers are associated with as high as 50% disease recurrence rate at 2 years. Since 1996 when concomitant radiotherapy and MMC (mytomicin C) and 5-FU-based chemotherapy demonstrated superiority to radiotherapy alone, no significant progress has been achieved in patients with locally advanced SCCA. Still, phase III study by James et al. reported in 2013 showed that prognosis of SCCA patients treated with this regimen can be improved probably due to a better tumor classification, more precise radiological methods, known as "Will Rogers phenomenon". Based on the above, investigators have designed this phase II trial assessing the feasibility and efficacy of Ezabenlimab (BI 754091) and mDCF chemotherapy combination followed by: * standard chemoradiotherapy in case of low response to induction treatment (\<30% by RECIST criteria) or * additional 2 cycles of mDCF and 1 cycle of Ezabenlimab (BI 754091) followed by hypofractionated radiotherapy in case of high response (≥ 30% by RECIST criteria) in SCCA patients with high-risk locally advanced (stage III) disease. In summary, the first innovative aspect of this research program is to provide a valuable proof of concept study evaluating the feasibility to combine radiotherapy, chemotherapies (docetaxel, cisplatin and 5-fluorouracil) and Ezabenlimab (BI 754091) in patients with stage III squamous cell anal carcinoma. INTERACT-ION study will provide evidence that Ezabenlimab (BI 754091) acts in synergy with mDCF to improve complete response rate, and both with hypofractionated radiotherapy to improve the disease-free survival enhancing TH1 and CD8 T cell immunity.

Conditions

• Squamous Cell Carcinoma of the Anus Stage III

Interventions

Type	Name	Description
BIOLOGICAL	Blood sample collection	A total of 9 EDTA (ethylenediaminetetraacetic acid) tubes will be collected at each time point to perform: PBMC collection: 6 EDTA tubes of 6 ml of peripheral blood mononuclear cell \[PBMC\] will be sent to the central laboratory (Biomonitoring Platform of Besançon, CHRU de Besançon located at Etablissement Français du Sang) at room temperature within 24 hours via an approved carrier for their processing, storage and immunomonitoring analysis. A sending sheet of the samples will be attached to each single sample. Plasma collection: One 6 ml EDTA tube should be frozen in each investigation center for plasma collection. Plasma for circulating tumoral DNA (ctDNA) collection: Two 4 ml EDTA tube should be frozen in each investigation center for ctDNA collection.
PROCEDURE	Biopsy	A tumor biopsy will be performed at 2 months after enrollment.

Timeline

• Start date: 2022-01-04
• Primary completion: 2024-11-21
• Completion: 2026-07-05
• First posted: 2021-01-22
• Last updated: 2024-12-20

Locations

10 sites across 1 country: France