Squamous Cell Carcinoma of the Anal CanalPhase 2TIRANUSNCT05661188
Tiraglolumab Atezolizumab and Chemoradiotherapy in Localized Anal Carcinoma (TIRANUS)
A Phase 2 study testing Atezolizumab plus Tiraglolumab in people with Squamous Cell Carcinoma of the Anal Canal, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 13 sites in Spain.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Squamous Cell Carcinoma of the Anal Canal
- What is being tested?
- Atezolizumab plus Tiraglolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 13 sitesSpain
- Study dates
- 14 Feb 2023to 25 Sep 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female subjects ≥ 18 years old.
- Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Histologically confirmed squamous cell carcinoma of the anal canal. This may include non-keratinizing histological subtypes (i.e. basaloid, transitional, spheroidal and cloacogenic).
- Locoregional squamous cell carcinoma of the anal canal with no distant metastasis: stages I, II, IIIA, and IIIB according to the American Joint Cancer Committee (AJCC) Cancer Staging Handbook Seventh Edition (T1-4, N0-1, M0). Patients with well differentiated Stage I anal margin cancer are not eligible.
- Mandatory archival or recent paraffin-fixed (FFPE) tumor biopsy available at baseline for translational purposes. Fine-needle biopsy is acceptable.
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- Note: If there is no archival tumor tissue or not enough tissue available from the biopsy at diagnosis, another biopsy may be requested before treatment begins (after signing the informed consent).
- At least one evaluable lesion.
- Patients should meet the criteria for radical chemoradiotherapy for squamous cell carcinoma of the anal canal following international guidelines.
- Normal life expectancy, excluding cancer mortality risk
- Patients with adequate normal organ and marrow function assessed within 14 days prior to start of the study treatment as defined below:
- Hemoglobin ≥ 9.0 g/dL (Patients may be transfused to meet this criterion).
- Absolute neutrophil count (ANC) > 1500 per mm3.
- Platelet count ≥ 100,000 per mm3.
- Serum total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology); however, they will be allowed only in consultation with their physician if total bilirubin ≤ 3 × ULN.
- Serum transaminases: alanina aminotransferase (ALT), aspartato aminotransferase (AST) and fosfatase alcalina (ALP) ≤ 2.5X ULN.
- Serum albumin ≥ 25 g/L (2.5 g/dL).
- Creatinine ≤ 1.5 mg/dL or measured creatinine clearance (CL) > 60 mL/min or Calculated creatinine CL > 60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for the determination of creatinine clearance:
- Males:
- Creatinine CL (mL/min) = (Weight (kg) × (140 - Age))/ 72 x serum creatinine (mg/dL)
- Females:
- Creatinine CL (mL/min) = ((Weight (kg) × (140 - Age) ×0.85))/72 x serum creatinine (mg/dL)
- Absence of active infection that requires systemic antibiotics.
- Female subjects of childbearing potential (WOCBP) must provide a negative urine pregnancy test at screening, and must agree to use a medically accepted and highly effective birth control method (i.e. those with a failure rate less than 1%) for the duration of the study treatment and for 90 days after the final dose of tiragolumab, 5 months after the final dose of atezolizumab, and 6 months after the final dose of cisplatin / 5-fluorouracil (5-FU).
- A woman is considered of childbearing potential ( i.e. fertile) following menarche and until becoming post-menopausal unless permanently sterile. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Amenorrheic for ≥1 year in the absence of chemotherapy and/or hormonal treatments
- Luteinizing hormone (LH) and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range
- Radiation induced oophorectomy with last menses >1 year ago
- Chemotherapy induced menopause with >1 year interval since last menses
- Surgical sterilization (bilateral oophorectomy or hysterectomy)
- Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
- Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- For both male and female patients/partners: Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study treatment and for 90 days after the final dose of tiragolumab, and 6 months after the final dose of cisplatin / 5-FU.
- A sterile male is defined as:
- One for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility.
- Males with known "low sperm counts" (consistent with "sub-fertility") are not to be considered sterile for purposes of this study.
- Willingness and ability of patients to comply with the protocol for the duration of the study including undergoing treatment as well as availability for scheduled visits and examinations including follow up.
Who cannot join
- Previous or pre-planned potentially curative surgery for the anal carcinoma for the duration of the study. Major surgery (i.e. cystectomy) less than 28 days prior to the first dose of study treatment.
- Prior treatment for the control of the squamous cell carcinoma of the anal canal. Prior radiotherapy, chemotherapy or treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies are not allowed.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the tiragolumab or atezolizumab formulation.
- History of allogeneic stem cell or solid organ transplant.
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis.
- Note: Subjects with the following are not excluded:
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- Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
- Rash must cover < 10% of body surface area.
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
- There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
- Subjects that have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment, with the exceptions:
- Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study
- Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
- Treatment with investigational therapy within 42 days prior to initiation of study treatment. Observational studies are permitted.
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2) within 28 days or 5 drug-elimination half-lives (whichever is longer) prior to first study treatment administration.
- Not stable treatment with anticoagulant therapies.
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety. Active tuberculosis, Epstein-Barr virus(EBV), Hepatitis C virus (HCV), Hepatitis B virus (HBV), or Human immunodeficiency virus (HIV). Current treatment with antiviral therapy for HBV.
- Note: HIV-positive patients may be eligible if they are stable as defined by (a) CD4+ count ≥ 300/μL. (b) Undetectable viral load per standard of care assay. (c) Receiving antiretroviral therapy (ART/HAART) for at least 4 weeks prior to study enrollment, and having not experienced any HIV-related opportunistic infection for at least 4 weeks prior to study enrollment.
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.
- Note: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
- Vaccination within 4 weeks of the first dose of study treatment, or anticipation of need for such a vaccine while on trial, and 5 months after last dose of atezolizumab and/or 90 days after last dose of tiragolumab is prohibited except for administration of inactivated vaccines (i.e. SARS-CoV-2 and Influenza vaccines will be permitted).
- Subject has a history of another uncontrolled malignancy before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy..
- Presence of the following conditions within the past 6 months:
- Uncontrolled diabetes
- Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
- New York Heart Association class II-IV congestive heart failure
- Cerebrovascular accident
- Transient ischemic attack
- Uncontrolled hypertension
- Unstable angina
- Myocardial infarction
- Grade ≥ 2 peripheral neuropathy as defined by NCI CTCAE v5.0 criteria
- Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage procedures
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis.
- Women pregnant or breastfeeding. Fertile and sexually active patients who are not willing to use the appropriate highly effective contraceptive methods.
- Any underlying medical or psychiatric disorder, which, in the opinion of the investigator, makes the administration of atezolizumab or tiragolumab unsafe or interferes with the informed consent process or trial procedures.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Spain13 sites
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08024
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona, 08024
Hospital General de Ciudad Real
Ciudad Real, Ciudad Real, 13005
Institut Català d'Oncologia (ICO) Hospitalet
L'Hospitalet de Llobregat, Barcelona, 08908
Complejo Asistencial Universitario de León
León, León, 24071
Hospital Arnau de Vilanova
Lleida, Barcelona, 25198
Hospital Universitario 12 de Octubre
Madrid, Madrid, 28041
HU Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Hospital Universitario Son Espases
Palma de Mallorca, Balearic Islands, 07120
Consorcio Corporación Sanitaria Parc Taulí
Sabadell, Barcelona, 08024
Hospital General Universitario de Toledo
Toledo, Castille-La Mancha, 45007
Hospital Universitario y Politécnico la Fe de Valencia
Valencia, Valencia, 46026
Hospital Universitario Miguel Servet
Zaragoza, Zaragoza, 50009
About this study
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.
Read more
The main question[s] it aims to answer are:
- 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.
- 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.
Read the detailed description
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.
- 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)
- Being tested
- Atezolizumab plus Tiraglolumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atezolizumab plus TiraglolumabDrug
All patients receive atezolizumab (1200mg) plus tiragolumab (600 mg) for 2 cycles (Q3W) in concomitance with the 6 weeks of standard scheduled chemoradiotherapy (cisplatin: 60 mg/m² on days 1 and 29; 5-FU: 1000 mg/m² per day on days 1-4 and 29-32; radiotherapy: 1.8 Gy per day / total dose 54 Gy). After the concomitant phase, patients receive atezolizumab and tiragolumab for 6 additional cycles (consolidation phase).
| Study group | Role | What they receive |
|---|---|---|
| atezolizumab and tiragolumab in concomitancy with standard chemoradiotherapy | Experimental | TIRANUS is a Phase II, single-arm, open-label, non-randomized, multicenter clinical trial of atezolizumab and tiragolumab in concomitance with standard chemoradiotherapy as first-line in treatment-naïve, localized squamous cell carcinoma of the anal canal who are candidates for radical chemoradiotherapy. Patients with well differentiated stage I anal margin cancer or previously treated with immunotherapy are not eligible.
All patients receive atezolizumab (1200mg) plus tiragolumab (600 mg) for 2 cycles (Q3W) in concomitance with the 6 weeks of standard scheduled chemoradiotherapy (cisplatin: 60 mg/m² on days 1 and 29; 5-FU: 1000 mg/m² per day on days 1-4 and 29-32; radiotherapy: 1.8 Gy per day / total dose 54 Gy). After the concomitant phase, patients receive atezolizumab and tiragolumab for 6 additional cycles (consolidation phase). Receives: Drug: Atezolizumab plus Tiraglolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical complete response (CCR)
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).
Measured: End of consolidation phase (week 26)
Clinical complete response (CCR) rate
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.
Measured: End of consolidation phase (week 26)
Secondary outcomes (16)
Locoregional failure rate (LFR)1
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
Measured: 1-year after the first dose of study treatment
Locoregional failure rate (LFR)2
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
Measured: 2 years after the first dose of study treatment
Locoregional failure rate (LFR)3
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
Measured: 3 years after the first dose of study treatment
Locoregional failure rate (LFR)5
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
Measured: at the end of study, approximately 5 years after the first dose of study treatment.
Disease-free survival (DFS)1
Disease-free survival (DFS): 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 median DFS and the DFS rate at 1, 2, and 3 years, at the end of study (approximately 5 years after the first dose of study treatment). 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. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment.
Measured: 1 year after the first dose of study treatment.
Disease-free survival (DFS)2
Disease-free survival (DFS): 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 median DFS and the DFS rate at 1, 2, and 3 years, at the end of study (approximately 5 years after the first dose of study treatment). 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. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment.
Measured: 2 years after the first dose of study treatment.
Disease-free survival (DFS)3
Disease-free survival (DFS): 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 median DFS and the DFS rate at 1, 2, and 3 years, at the end of study (approximately 5 years after the first dose of study treatment). 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. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment.
Measured: 3 years after the first dose of study treatment.
Disease-free survival (DFS)5
Disease-free survival (DFS): 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 median DFS and the DFS rate at 1, 2, and 3 years, at the end of study (approximately 5 years after the first dose of study treatment). 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. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment.
Measured: And at the end of study, approximately 5 years after the first dose of study treatment.
Colostomy-free survival (CFS)1
Colostomy-free survival (CFS): 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 investigators will assess the median CFS and the CFS rate at 1, 2, and 3 years, and at the end of study (approximately 5 years after the first dose of study treatment). 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. Patients alive and free of events at the date of the analysis will be censored at their last known contact.
Measured: 1-year after the first dose of study treatment
Colostomy-free survival (CFS)2
Colostomy-free survival (CFS): 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 investigators will assess the median CFS and the CFS rate at 1, 2, and 3 years, and at the end of study (approximately 5 years after the first dose of study treatment). 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. Patients alive and free of events at the date of the analysis will be censored at their last known contact.
Measured: 2-year after the first dose of study treatment
Colostomy-free survival (CFS)3
Colostomy-free survival (CFS): 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 investigators will assess the median CFS and the CFS rate at 1, 2, and 3 years, and at the end of study (approximately 5 years after the first dose of study treatment). 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. Patients alive and free of events at the date of the analysis will be censored at their last known contact.
Measured: 3-year after the first dose of study treatment
Colostomy-free survival (CFS)5
Colostomy-free survival (CFS): 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 investigators will assess the median CFS and the CFS rate at 1, 2, and 3 years, and at the end of study (approximately 5 years after the first dose of study treatment). 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. Patients alive and free of events at the date of the analysis will be censored at their last known contact.
Measured: At the end of study, approximately 5 years after the first dose of study treatment.
Overall survival (OS)3
Overall survival (OS): defined as the time elapsed from the first dose of study treatment until death from any cause. The investigators will assess the median OS and 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. Patients alive and free of events at the date of the analysis will be censored at their last known contact.
Measured: 3-years after the first dose of study treatment
Overall survival (OS)5
Overall survival (OS): defined as the time elapsed from the first dose of study treatment until death from any cause. The investigators will assess the median OS and 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. Patients alive and free of events at the date of the analysis will be censored at their last known contact.
Measured: 5-years after the first dose of study treatment
Incidence of adverse events (AEs)
To evaluate safety of the intended treatment regimen based on the frequency and severity of adverse events (AE) assessed by NCI CTCAE v5.0. Incidence of adverse events (AEs) evaluated as percentage of patients experiencing an adverse event.
Measured: Throughout the study period, approximately 5 years per patient
Incidence of Treatment-emergent adverse events (TEAEs)
To evaluate safety of the intended treatment regimen based on the frequency and severity of Treatment-emergent adverse events (TEAEs) assessed by NCI CTCAE v5.0. Incidence of Treatment-emergent adverse events (TEAEs) evaluated as percentage of patients experiencing an treatment-emergent adverse events.
Measured: Throughout the study period, approximately 5 years per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2022
- Study start14 Feb 2023
- Primary completion25 Sep 2026
- Study completion25 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of the Anal CanalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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-FU, and Cisplatin) as first-line in localized squamous cell carcinoma of the anal canal.
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol Multidisciplinario del Cancer Digestivo
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Jaume Capdevila, Study chair, Hospital Vall d'Hebron
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05661188
- Sponsor's protocol ID
- GEMCAD - 2103 // MO44170
- Acronym
- TIRANUS
- Status last verified
- Oct 2026
- First submitted
- 30 Nov 2022
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The individual participant data (IPD) anonymized could be shared upon request if the use is within the scope and protection level authorized by the patients by the signature of the informed consent
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Atezolizumab Plus Tiraglolumab in Combination With Chemoradiotherapy in Localized Squamous Cell Carcinoma of the Anal Canal
- ClinicalTrials.gov ID
- NCT05661188
- Acronym / sponsor ID
- TIRANUS / GEMCAD - 2103 // MO44170
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Grupo Espanol Multidisciplinario del Cancer DigestivoUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 14 Feb 2023 (actual)
- Primary completion
- 25 Sep 2026 (actual)
- Study completion
- 25 Sep 2026 (actual)
- First posted
- 22 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
Detailed description
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.
- 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)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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-FU, and Cisplatin) as first-line in localized squamous cell carcinoma of the anal canal.
| Arm | Type | Receives |
|---|---|---|
| atezolizumab and tiragolumab in concomitancy with standard chemoradiotherapy | Experimental | Drug: Atezolizumab plus TiraglolumabTIRANUS is a Phase II, single-arm, open-label, non-randomized, multicenter clinical trial of atezolizumab and tiragolumab in concomitance with standard chemoradiotherapy as first-line in treatment-naïve, localized squamous cell carcinoma of the anal canal who are candidates for radical chemoradiotherapy. Patients with well differentiated stage I anal margin cancer or previously treated with immunotherapy are not eligible. All patients receive atezolizumab (1200mg) plus tiragolumab (600 mg) for 2 cycles (Q3W) in concomitance with the 6 weeks of standard scheduled chemoradiotherapy (cisplatin: 60 mg/m² on days 1 and 29; 5-FU: 1000 mg/m² per day on days 1-4 and 29-32; radiotherapy: 1.8 Gy per day / total dose 54 Gy). After the concomitant phase, patients receive atezolizumab and tiragolumab for 6 additional cycles (consolidation phase). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Male or female subjects ≥ 18 years old.
- Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Histologically confirmed squamous cell carcinoma of the anal canal. This may include non-keratinizing histological subtypes (i.e. basaloid, transitional, spheroidal and cloacogenic).
- Locoregional squamous cell carcinoma of the anal canal with no distant metastasis: stages I, II, IIIA, and IIIB according to the American Joint Cancer Committee (AJCC) Cancer Staging Handbook Seventh Edition (T1-4, N0-1, M0). Patients with well differentiated Stage I anal margin cancer are not eligible.
Key exclusion criteria (39 listed)
- Previous or pre-planned potentially curative surgery for the anal carcinoma for the duration of the study. Major surgery (i.e. cystectomy) less than 28 days prior to the first dose of study treatment.
- Prior treatment for the control of the squamous cell carcinoma of the anal canal. Prior radiotherapy, chemotherapy or treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies are not allowed.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the tiragolumab or atezolizumab formulation.
- History of allogeneic stem cell or solid organ transplant.
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atezolizumab plus TiraglolumabAll patients receive atezolizumab (1200mg) plus tiragolumab (600 mg) for 2 cycles (Q3W) in concomitance with the 6 weeks of standard scheduled chemoradiotherapy (cisplatin: 60 mg/m² on days 1 and 29; 5-FU: 1000 mg/m² per day on days 1-4 and 29-32; radiotherapy: 1.8 Gy per day / total dose 54 Gy). After the concomitant phase, patients receive atezolizumab and tiragolumab for 6 additional cycles (consolidation phase). | Drug | atezolizumab and tiragolumab in concomitancy with standard chemoradiotherapy |
Primary outcome
Clinical complete response (CCR)
Time frame: 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
Time frame: 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.
16 secondary outcomes
Locoregional failure rate (LFR)1
Time frame: 1-year after the first dose of study treatment
Locoregional failure rate (LFR)2
Time frame: 2 years after the first dose of study treatment
Locoregional failure rate (LFR)3
Time frame: 3 years after the first dose of study treatment
Locoregional failure rate (LFR)5
Time frame: at the end of study, approximately 5 years after the first dose of study treatment.
Disease-free survival (DFS)1
Time frame: 1 year after the first dose of study treatment.
Disease-free survival (DFS)2
Time frame: 2 years after the first dose of study treatment.
Disease-free survival (DFS)3
Time frame: 3 years after the first dose of study treatment.
Disease-free survival (DFS)5
Time frame: And at the end of study, approximately 5 years after the first dose of study treatment.
Colostomy-free survival (CFS)1
Time frame: 1-year after the first dose of study treatment
Colostomy-free survival (CFS)2
Time frame: 2-year after the first dose of study treatment
Colostomy-free survival (CFS)3
Time frame: 3-year after the first dose of study treatment
Colostomy-free survival (CFS)5
Time frame: At the end of study, approximately 5 years after the first dose of study treatment.
Overall survival (OS)3
Time frame: 3-years after the first dose of study treatment
Overall survival (OS)5
Time frame: 5-years after the first dose of study treatment
Incidence of adverse events (AEs)
Time frame: Throughout the study period, approximately 5 years per patient
Incidence of Treatment-emergent adverse events (TEAEs)
Time frame: Throughout the study period, approximately 5 years per patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Individual participant dataSharing planned: No. The individual participant data (IPD) anonymized could be shared upon request if the use is within the scope and protection level authorized by the patients by the signature of the informed consent
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaume Capdevila study chair
Hospital Vall d'Hebron
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atezolizumab plus Tiraglolumab in people with Squamous Cell Carcinoma of the Anal Canal, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 13 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical complete response (CCR) (time frame: End of consolidation phase (week 26)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.