Preoperative Immunotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAlain Algazi
About this trial
To determine the effect of neoadjuvant atezolizumab alone or in combination with other immune modulating agents on T-cell infiltration in advanced SCCHN. To determine the impact of neo-adjuvant immunotherapy on surgical outcomes.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have clinically suspected SCCHN that is amenable to surgical resection with therapeutic intent
Be willing and able to provide written informed consent/assent for the trial
Be >=18 years of age on day of signing informed consent.
Agree to research analysis of an existing pre-treatment biopsy available that was obtained within 90 days prior to the day of consent or agree to a new biopsy for research (or clinical diagnosis) within the screening window. Needle biopsies must be at least 20 Gauge in diameter
Disqualifiers
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Participants who have received acute and/or low-dose systemic immunosuppressive medications (e.g., a one-time dose of dexamethasone for nausea or chronic use of <=10 mg/day of prednisone or dose-equivalent corticosteroid) may be enrolled in the study after discussion with and approval by the Sponsor. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed
Has a known history of active Bacillus tuberculosis (TB).
Has an acute primary infection or reactivation of Epstein-Barr virus (EBV).
Trial design
Design model
Sequential
Treatments tested in this trial
Atezolizumab
Biological/VaccineGiven intravenously (IV)
Tocilizumab
Biological/VaccineGiven IV
Tiragolumab
Biological/VaccineGiven IV
Treatment groups
55 Participants
are divided into 4 treatment groupsGroup A: Atezolizumab MonotherapyExperimental treatment 1 intervention
Group B: Atezolizumab (Adjuvant)Experimental treatment 1 intervention
Group C: Atezolizumab + TiragolumabExperimental treatment 2 interventions
Group D: Atezolizumab + TocilizumabExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Proportion of subjects with a >= 40% increase in the cluster of differentiation 3 (CD3) counts
Intratumoral CD3+ T-cells will be identified by immunohistochemistry in pre- and post-treatment tumor specimens. The analysis population for the primary outcome will be all patients who received at least 2 weeks of neoadjuvant therapy with pre- and post-treatment tumor specimens that are evaluable for CD3+ T-cells. The proportion of patients with a \>= 40% increase (from pre- to post-treatment) will be calculated. The exact 95% confidence intervals (CIs) using the Pearson-Clopper method and an exact binomial test will be used as an exploratory purpose. The change from pre-treatment to post-treatment CD3 count per mm\^3 as a continuous measure will also be summarized.
Time frame
Up to 2 years2
R0 resection rate
Patients who undergo surgery will be evaluable for R0 resection rate. R0 resection rate will be described by point estimate and 95% CI using the Pearson-Clopper method.
Time frame
Up to 2 yearsSecondary outcomes
1
Changes in immune parameters using mass cytometry (CyTOF), histology and gene expression
The study will describe immune parameters at each time point by median and interquartile range (IQR) and compare the change between pre-treatment and surgical specimens by Wilcoxon singed rank test. Diversity of T-cell repertoires at each time point will be evaluated by clonality and compared by Wilcoxon singed ranked test. Moristas' distance will also be used to assess the change of T-cell repertoires.
Time frame
Up to 2 years2
Changes in peripheral immune responses using CyTOF
The study will describe immune parameters at each time point by median and IQR and compare the change between pre-treatment and surgical specimens by Wilcoxon singed rank test.
Time frame
Up to 1 year post surgery3
Number of participants with treatment-related adverse events
Treatment-related adverse events will be classified according to Common Terminology Criteria for Adverse Events version 5. Evaluation of Safety Analyses will be performed for all patients having received at least one dose of treatment on study.
Time frame
Up to 30 days post-treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Alain Algazi
Lead sponsor
University of California, San Francisco
Sponsor institution
Genentech, Inc.
Collaborator
American Head and Neck Society
Collaborator
Source ClinicalTrials.gov