Tiraglolumab Atezolizumab and Chemoradiotherapy in Localized Anal Carcinoma (TIRANUS)

NCT05661188 | Recruiting Phase 2

• 1 other identifier: GEMCAD - 2103 // MO44170
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 15

Brief 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 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. 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. 2.To evaluate safety of the intended treatment regimen and Health-related quality of life (HRQoL) in this treatment regimen

Conditions

Squamous Cell Carcinoma of the Anal Canal

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  End of consolidation phase (week 26)

Secondary Outcomes (16)

• Locoregional failure rate (LFR)1

  1-year after the first dose of study treatment

• Locoregional failure rate (LFR)2

  2 years after the first dose of study treatment

• Locoregional failure rate (LFR)3

  3 years after the first dose of study treatment

• Locoregional failure rate (LFR)5

  at the end of study, approximately 5 years after the first dose of study treatment.

• Disease-free survival (DFS)1

  1 year after the first dose of study treatment.

Other Outcomes (2)

• Health-related quality of life (HRQoL)

  concomitant phase (week1); consolidation phase (week 7) and after the end of treatment (week 24)

• Determination of the most frequent molecular alterations in this pathology

  During the screening, and after the end of treatment (Week 26).

Study Arms (1)

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).

Drug: Atezolizumab plus Tiraglolumab

Interventions

Atezolizumab plus Tiraglolumab DRUG

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).

atezolizumab and tiragolumab in concomitancy with standard chemoradiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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:
• 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:
• i. Rash must cover \< 10% of body surface area.
• ii. Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• iii. 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.

Sponsors & Collaborators

• Grupo Espanol Multidisciplinario del Cancer Digestivo: lead
• Hoffmann-La Roche: collaborator

Study Sites (15)

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

RECRUITING

Institut Català d'Oncologia (ICO) Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital Arnau de Vilanova

Lleida, Barcelona, 25198, Spain

RECRUITING

Hospital Sant Joan Despí

Martorell, Barcelona, 08970, Spain

RECRUITING

Consorcio Corporación Sanitaria Parc Taulí

Sabadell, Barcelona, 08024, Spain

RECRUITING

Hospital General Universitario de Toledo

Toledo, Castille-La Mancha, 45007, Spain

RECRUITING

HU Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08024, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08024, Spain

RECRUITING

Hospital General de Ciudad Real

Ciudad Real, 13005, Spain

RECRUITING

Complejo Asistencial Universitario de León

León, 24071, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Consorcio Hospital General Universitario de Valencia

Valencia, 46014, Spain

RECRUITING

Hospital Universitario y Politécnico la Fe de Valencia

Valencia, 46026, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

RECRUITING

MeSH Terms

Interventions

atezolizumab

Study Officials

• Jaume Capdevila

  Hospital Vall d'Hebron

  STUDY CHAIR

Central Study Contacts

A responsible person Designated by the Sponsor

CONTACT

+34 93 434 44 12; investigacion@mfar.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: December 22, 2022
• Study Start: February 14, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15)