Phase II Study of Atezolizumab Plus Tiraglolumab in Combination With Chemoradiotherapy in Localized Squamous Cell Carcinoma of the Anal Canal (TIRANUS)

NCT05661188 Phase 2 RECRUITING

The peculiarity of anal cancers, with well-established radical chemoradiotherapy that allows tumor-neoantigen formation with platinum-based chemotherapy and radiotherapy with radio-sensitizing chemotherapy could create the perfect environment for immunotherapy in this setting, not only to increase the probability of pathological complete response (CCR) but also creating neoantigen exposure and immune-prevention to reduce the relapse after surgery. TIRANUS trial is a Phase II, single-arm, open-label, non randomized, non controlled recruiting treatment-naive localized squamous cell carcinoma of the anal canal and are candidates for radical chemoradiotherapy. The trial hypothesizes that the addition of immunotherapy (atezolizumab and tiragolumab) to standard chemoradiotherapy in localized squamous cell carcinoma of the anal canal may improve the CCR at the end of consolidation phase. The study will assess, as the primary endpoint, the CCR, defined as the percentage of patients who have achieved complete response (CR), disappearance of all target lesions and no presence of residual disease assessed by biopsy at the end of consolidation phase. Secondary objectives include survival, safety of the combination, patient reported quality of life, and a substudy of molecular biomarkers determined in tumor biopsy and blood samples. The main question\[s\] it aims to answer are: 1. To determine the efficacy of atezolizumab plus tiragolumab concomitantly with chemoradiotherapy in patients with localized squamous cell carcinoma of the anal canal evaluating the clinical response to treatment. 2. To evaluate safety of the intended treatment regimen and Health-related quality of life (HRQoL) in this treatment regimen All patients will receive atezolizumab plus tiragolumab for 2 cycles in concomitance with the 6 weeks of standard scheduled chemoradiotherapy. (cisplatin, 5-Fluorouracil and radiotherapy). After the concomitant phase, patients will enter a consolidation phase and will receive atezolizumab in combination with tiragolumab up to 24 weeks. Patients will discontinue treatment in case of confirmed progression, toxicity, patient criteria, or physician criteria.

Details

Lead sponsor	Grupo Espanol Multidisciplinario del Cancer Digestivo
Phase	Phase 2
Status	RECRUITING
Enrolment	45
Start date	2023-02-14
Completion	2028-06

Conditions

• Squamous Cell Carcinoma of the Anal Canal

Interventions

• Atezolizumab plus Tiraglolumab

Primary outcomes

• Clinical complete response (CCR) — End of consolidation phase (week 26)
  Clinical complete response (CCR), defined as the percentage of patients who have achieved complete response (CR), disappearance of all lesions according to RECIST 1.1 criteria (locally assessed by the PI) and no presence of residual disease assessed by biopsy at the end of consolidation phase (week 26).
• Clinical complete response (CCR) rate — End of consolidation phase (week 26)
  Clinical response rate: Patients will be classified as responders (complete or partial responders) and non-responders based on: 1) the presence of residual disease on tumor biopsy and 2) CT or MRI scans post-treatment (week 26). The binomial proportion and its 95% confidence interval will be used to estimate the CCR rate. Logistic regression analysis will be used to evaluate the effect of baseline characteristics and other covariates with response rate.

Countries

Spain