Preoperative Immunotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck

NCT03708224 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 177018NCI-2018-01992ML40180
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer; Carcinoma; Squamous Cell Carcinoma; Head and Neck Cancer

Keywords

Cancer; Non-Virally Associated Squamous Cell Carcinoma; Head and Neck

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 2 years

• 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.

  Up to 2 years

Secondary Outcomes (3)

• Changes in immune parameters using mass cytometry (CyTOF), histology and gene expression

  Up to 2 years

• Changes in peripheral immune responses using CyTOF

  Up to 1 year post surgery

• Number of participants with treatment-related adverse events

  Up to 30 days post-treatment

Study Arms (4)

Atezolizumab Monotherapy

EXPERIMENTAL

Participants will receive 840mg of atezolizumab over 15 days prior to definitive surgery.

Biological: Atezolizumab

Atezolizumab (Adjuvant)

EXPERIMENTAL

Participants will receive 840mg of atezolizumab over 15 days prior to definitive surgery. The first 9 participants in Arm A (atezolizumab monotherapy) will also receive adjuvant atezolizumab 16 weeks after standard of care surgery and radiation, or chemoradiation therapy, at a fixed dose of 1200 mg IV every 3 weeks for an additional 12 cycles.

Biological: Atezolizumab

Atezolizumab + Tiragolumab

EXPERIMENTAL

Participants will receive 840 mg of atezolizumab IV and 600 mg of Tiragolumab during the 15-day neoadjuvant period prior to definitive surgery.

Biological: Atezolizumab; Biological: Tiragolumab

Atezolizumab + Tocilizumab

EXPERIMENTAL

Participants will receive 840 mg of atezolizumab IV and 6 mg/kg of Tocilizumab during the 15-day neoadjuvant period prior to definitive surgery.

Biological: Atezolizumab; Biological: Tocilizumab

Interventions

Atezolizumab BIOLOGICAL

Given intravenously (IV)

Also known as: Tecentriq

Atezolizumab (Adjuvant); Atezolizumab + Tiragolumab; Atezolizumab + Tocilizumab; Atezolizumab Monotherapy

Tocilizumab BIOLOGICAL

Given IV

Also known as: Actemra

Atezolizumab + Tocilizumab

Tiragolumab BIOLOGICAL

Given IV

Also known as: anti-TIGIT

Atezolizumab + Tiragolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Demonstrate adequate organ function as defined below. All screening labs should be performed within 14 days of treatment initiation
• Absolute neutrophil count (ANC) \>=1,500 /microliter (mcL)
• Platelets \>=100,000 / mcL
• Hemoglobin \>= 9 g/dL
• Lymphocyte count \>= 500/mcL
• White blood count \>=3,000/mcL or \<=14,000/mcL
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR ≥50 mL/min creatinine clearance by Cockcroft-Gault formula for participants in whom, in the Investigator's judgment, serum creatinine levels do not adequately reflect renal function. \* Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) \[serum glutamic-oxaloacetic transaminase (SGOT)\] and alanine aminotransferase (ALT) \[serum glutamate pyruvate transaminase (SGPT)\] =\< 3 x ULN
• Albumin \>= 2.5 mg/dL

You may not qualify if:

• 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).
• Known allergy or hypersensitivity to any of the study drugs or their excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent or radiation therapy
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, low-grade thyroid cancer and prostate cancer that is in remission under androgen deprivation-therapy for \> 2 years or under watchful waiting with Prostate-specific antigen (PSA) doubling time \> 6 months. Additional malignancies may be permitted after consultation with the Principal Investigator. Other exceptions may apply and require discussion between the Investigator and the Sponsor
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis requiring corticosteroids
• Patient has known history of stage 2 or higher chronic obstructive pulmonary disease (COPD). Stage 2 COPD is defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) \< 70%; 50% \< FEV1 \< 80% predicted, with dyspnea on exertion
• Patient has asthma requiring systemic corticosteroids at the time of screening. Inhaled corticosteroids for the treatment of asthma are permitted
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known medical, psychiatric or substance abuse disorders/conditions that in the opinion of the principal investigator would interfere with cooperation or interfere with safe completion of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

Sponsors & Collaborators

• Alain Algazi: lead
• Genentech, Inc.: collaborator
• American Head and Neck Society: collaborator

Study Sites (1)

University of San Francisco, California

San Francisco, California, 94143, United States

RECRUITING

Related Publications (1)

• Rahim MK, Okholm TLH, Jones KB, McCarthy EE, Liu CC, Yee JL, Tamaki SJ, Marquez DM, Tenvooren I, Wai K, Cheung A, Davidson BR, Johri V, Samad B, O'Gorman WE, Krummel MF, van Zante A, Combes AJ, Angelo M, Fong L, Algazi AP, Ha P, Spitzer MH. Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell. 2023 Mar 16;186(6):1127-1143.e18. doi: 10.1016/j.cell.2023.02.021.

  PMID: 36931243 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Interventions

atezolizumab; tocilizumab; Tiragolumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Neoplasms by Site

Study Officials

• Alain Algazi, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF HDFCCC Cancer Immunotherapy Program (CIP)

CONTACT

(877) 827-3222; HDFCCC.CIP@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 17, 2018
• Study Start: March 8, 2019
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 28, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)