Squamous Cell Carcinoma of the Anal Canal Clinical Trial
Official title:
Phase II Study of Atezolizumab Plus Tiraglolumab in Combination With Chemoradiotherapy in Localized Squamous Cell Carcinoma of the Anal Canal
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.
The TIRANUS trial is a Phase II, single-arm, open-label, non randomized, non controlled, proof-of-concept clinical trial of atezolizumab and tiragolumab in concomitancy with standard chemoradiotherapy (RT, 5-Fluorouracil, and Cisplatin) as first-line in localized squamous cell carcinoma of the anal canal. 1. Objectives 1.1 Primary Objectives To determine if atezolizumab plus tiragolumab in concomitancy with chemoradiotherapy is effective in achieving complete remission in patients with localized squamous cell carcinoma of the anal canal assessed by means of 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 and no presence of residual disease assessed by biopsy at the end of consolidation phase (week 26). 1.2. Secondary Objectives Efficacy secondary objectives: - To evaluate the locoregional failure rate (LFR), defined as the percentage of patients who present progression/relapse of disease in the anal canal and/or regional organs and/or regional lymph nodes. Locoregional failure rate will be estimated using the appropriate logistic regression model at 1-year, 2-years, and 3-years after the first dose of study treatment and end of study. - To evaluate the disease-free survival (DFS) of patients with localized squamous cell carcinoma of the anal canal, defined as the time elapsed from the first dose of study treatment to progression, relapse, or death from any cause, whichever occurs first. The investigators will assess the DFS rate at 1, 2, and 3 years. The 1-year, 2-years, and 3-years DFS rates are defined as the rate of patients alive and free of relapse or progression at 1, 2, and 3 years after the first dose of study treatment respectively, estimated by Kaplan-Meier. - To evaluate the colostomy-free survival (CFS) of patients with localized squamous cell carcinoma of the anal canal, defined as the time elapsed from the first dose of study treatment to the date the colostomy was required or death from any cause, whichever occurs first. The 1-year, 2-years, and 3-years CFS rates are defined as the rate of patients alive and free of colostomy at 1, 2, and 3 years after the first dose of study treatment respectively, estimated by Kaplan-Meier. - To determine the overall survival (OS) of patients with localized squamous cell carcinoma of the anal canal, defined as the time elapsed from the first dose of study treatment until death from any cause. The investigators will assess the OS rate at 3 and 5 years. The 3-years and 5-years OS rates are defined as the rate of patients alive at 3 and 5 years after the first dose of study treatment respectively, estimated by Kaplan-Meier. Safety secondary objectives - To evaluate safety of the intended treatment regimen based on the frequency and severity of adverse events and Treatment-emergent adverse events (TEAEs) assessed by NCI CTCAE v5.0. - Health-related quality of life (HRQoL), assessed through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) version 3. Exploratory objectives - To determine molecular or clinical predictive biomarkers of clinical complete response. - To evaluate the relationship between the treatment activity and the expression of: - Immune checkpoint proteins (including but not limited to PD-1, PD-L1, CD28, OX40, CD40) - Presence of infiltrating T cell lymphocytes and immune infiltrate characterization (including but not limited to CD45, CD3, CD8, CD4, CD56, IFNbeta, STAT1, CD 163, H2AX) - T-cell clonality (TCR) by multiplex PCR-based clonality (polymerase chain reaction amplification based clonality) // NGS (Next-Generation Sequencing) - Tumor mutational burden (TMB) by means of a gene panel with >300 genes. - Presence of infections: poliovirus receptor (PVR) and human papillomavirus (HPV) - Presence of potential molecular biomarkers in ctDNA (including but not limited to HPV, KRAS, or TP53) ;
| Status | Clinical Trial | Phase | |
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| Completed |
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| Active, not recruiting |
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Phase 3 |