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Tiraglolumab Atezolizumab and Chemoradiotherapy in Localized Anal Carcinoma (TIRANUS)

ConditionSquamous Cell Carcinoma of the Anal Canal
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGrupo Espanol Multidisciplinario del Cancer Digestivo

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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).

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • 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).

Treatment groups

45 Participants
are divided into 1 treatment group
Group A: atezolizumab and tiragolumab in concomitancy with standard chemoradiotherapyExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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).

Time frame
End of consolidation phase (week 26)
2

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.

Time frame
End of consolidation phase (week 26)

Secondary outcomes

1

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

Time frame
1-year after the first dose of study treatment
2

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

Time frame
2 years after the first dose of study treatment
3

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

Time frame
3 years after the first dose of study treatment
4

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

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

Other outcomes

1

Health-related quality of life (HRQoL)

The EORTC QLQ-C30 questionnaire is a specific questionnaire validated for cancer that is composed of 30 questions or items. The questionnaire is structured in 5 functional scales (physical functioning, daily activities, emotional functioning, cognitive functioning and social functioning), 3 symptom scales (fatigue, pain and nausea, vomiting), 1 global health status scale, and 6 independent items (dyspnea, insomnia, anorexia, constipation, diarrhea and economic impact). Values between 1 and 4 (1: not at all, 2: a little, 3: quite, 4: a lot) are assigned according to the patient's responses to the item, only in items 29 and 30 are they evaluated with a score of 1 to 7 (1: dreadful, 7: excellent). The scores obtained are standardized and a score between 0 and 100 is obtained, which determines the level of impact of the cancer on the patient on each of the scales. A higher score indicating a better HRQoL.

Time frame
concomitant phase (week1); consolidation phase (week 7) and after the end of treatment (week 24)
2

Determination of the most frequent molecular alterations in this pathology

Percentage of patients presenting alterations or deregulation in any of the following (composite endpoint) * The expression of immune checkpoint proteins (PD-1, PD-L1, CD28, OX40, CD40, or others) in blood and tumor samples. * The expression of potential molecular biomarkers (HPV, KRAS, TP53) in liquid biopsy (ctDNA) and tumor samples. * The expression of poliovirus receptor (PVR) and HPV status. * The presence of infiltrating T cell lymphocytes (CD45, CD3, CD8, CD4, CD56, IFNbeta, STAT1,CD 163, H2AX, or others) in tumor samples. * The T-cell clonality (TCR) in blood samples * The presence of ctDNA in blood samples

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Grupo Espanol Multidisciplinario del Cancer Digestivo

Lead sponsor

Hoffmann-La Roche

Collaborator

Source ClinicalTrials.gov
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