Active — Not RecruitingPhase 2

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

France55 participantsStarted 2022-01-04

Plain-language 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.

Who can participate

Age range18 Years

SexALL

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Inclusion Criteria: * Signed and dated informed consent, * Age ≥18 years, * Ability to comply with the study protocol in the Investigator's judgment, * Performance status ECOG-WHO ≤ 1, * Histologically proved squamous cell anal carcinoma, * Locally advanced disease defined as: * Stage III (TxN1 or T4N0). Lymph node can be considered positive if one of the following criteria is satisfied: * Enlargement (largest short-axis diameter \> 1 cm for mesorectal nodes, and \> 1.5 cm for other nodes) OR, * Heterogeneity or necrosis OR, * Irregular contours OR, * Strong enhancement at magnetic resonance imaging (MRI) OR, * Positivity on positron emission tomography (PET) scan, * Patient eligible to the mDCF regimen, * Computed tomography (CT) scan performed within 30 days prior inclusion, * MRI of pelvis performed within 30 days prior inclusion, * PET scan performed within 30 days prior inclusion, * Adequate hematologic and end-organ function: defined by the following laboratory test results obtained within 7 days prior to initiation of study treatment: * Absolute neutrophil count (ANC) ≥ 1.5 X 109/L (1500/µL), * Platelet count ≥ 100 X 109/L (100.000/µL) without transfusion, * Hemoglobin ≥ 90 g/L (9g/dL); previous transfusion is allowed, * Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 X upper limit of normal (ULN), (≤ 5 X upper limit of normal (ULN) if known liver metastases) * Serum bilirubin ≤ 2.5 X ULN (except patients with known G…

What they're measuring

Clinical complete response (cCR) at 10 months

Timeframe: 10 months

Trial details

NCT IDNCT04719988

SponsorCentre Hospitalier Universitaire de Besancon

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-11-21