Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Anus Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Anal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anticoagulants

Docetaxel

Fluorouracil

Capecitabine

Cisplatin

Immunomodulating Agents

Mitomycins

Mitomycin

Edetic Acid

Pentetic Acid

Induction treatment

* Modified DCF: every 2 weeks for 8 cycles Docetaxel (40 mg/m², day 1), Cisplatin (40 mg/m², day 1) , 5-FU (1200 mg/m²/day for 2 days)
* Ezabenlimab: 240 mg intravenous, every 3 weeks for 3 cycles

In case of tumor response:

* Two additional cycles of mDCF and one additional cycle of Ezabenlimab (Q3W).
* Hypofractionated radiotherapy
* Ezabenlimab: 240 mg intravenous, every 3 weeks for 7 cycles

In absence of tumor response:

o Chemoradiotherapy (Intensity-Modulated Radiation Therapy \[IMRT\]) treatment: Chemoradiotherapy using IMRT will begin 3-4 weeks following the last cycle of induction phase, in the absence of toxicities of grade 1 and/or management of toxicities. It will last 7 weeks and will consist of:

• Standard dose of 45 Gy in 25 fractions over 5 weeks followed by a sequential boost of 14.4 Gy in 8 sessions,

Concomitantly given with:

* Capecitabine (825 mg/m²/orally twice daily) from Monday to Friday,
* Mitomycin C (10 mg/m² Day 1)

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.

Blood sample collection

A tumor biopsy will be performed at 2 months after enrollment.

Biopsy

Stefano KIM, Pr

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.

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

The primary endpoint is the Clinical complete response (cCR) 10 months from the treatment initiation (the best time to evaluate the local response is 26 weeks from the commencement of standard CRT. In this protocol, with the neoadjuvant treatment, additional 14 weeks are necessary; ie 10 months). cCR rate at 10 months is defined as the number of patients alive without clinically detectable lesion and no residual disease by MRI or CT scan assessment at 10 months divided by the overall number of patients evaluable for cCR status at 10 months.

A patient is evaluable for cCR status at 10 months if he dies during the 10 months of follow up or if he is alive with a RECIST evaluation available at 10 months.

Boehringer Ingelheim

Centre Hospitalier Universitaire de Besancon

Spots Global Cancer Trial Database for squamous cell carcinoma of the anus stage iii