Pre-operative Atezolizumab in Patients With Resectable, Human Papillomavirus Related Oropharyngeal Carcinoma

NCT06254911 | Suspended Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00004678NCI-2023-01367WINSHIP5730-22P30CA138292
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well atezolizumab works in treating patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma that is able to be removed with surgery (resectable). Immunotherapy with atezolizumab, may include changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

Conditions

Oropharynx Cancer, Stage I

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment-emergent adverse events

  From the first dose of study drug to 30 days after the last dose of the study drug

• Pathologic response

  Defined as human papillomavirus (HPV) circulating tumor deoxyribonucleic acid (ctDNA) level by interval change in pre- versus post-treatment HPV ctDNA level.

  After cycle 2 (each cycle is 21 days) and prior to surgery (for ctDNA changes) and on final pathologic analysis 14 days after surgery

• Event-free survival (EFS)

  Defined as the time from the first administration of 2 doses of single agent atezolizumab to the date of recurrence or death due to any cause, and patients who did not experience recurrence or death will be censored at the last evaluable disease assessment. The EFS distribution will be estimated by constructing a Kaplan-Meier curve with estimation of 2-year EFS rate and 95% CI.

  From the first administration of atezolizumab to date of recurrence, death or up to 2 years

Secondary Outcomes (1)

• Association of biomarkers with pathological response status

  Up to 2 years

Study Arms (1)

Treatment (Atezolizumab)

EXPERIMENTAL

Patients receive atezolizumab IV while on study. Patients undergo CT scan and MRI throughout the study. Patients may undergo tumor biopsy while on study.

Biological: Atezolizumab; Procedure: Transoral Surgery with cervical lymphadenctomy (neck dissection); Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (Atezolizumab)

Transoral Surgery with cervical lymphadenctomy (neck dissection) PROCEDURE

Undergo definitive surgical treatment to remove cancer from the tonsil or tongue base combined with removal of the at risk lymph nodes in the neck

Treatment (Atezolizumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (Atezolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (Atezolizumab)

Eligibility Criteria

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

You may qualify if:

• The subject is \>= 18 years old on the day of consent
• Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 5 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 5 months after the last dose of study drug(s).
• Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
• A male participant must agree to use a contraception as detailed in this protocol during the treatment period and for at least during the active treatment plus an additional 90 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose\] after the last dose of study treatment and refrain from donating sperm during this period.
• The subject has a histologic or cytologic diagnosis of squamous cell carcinoma of the oropharynx, Stage 1 (T1/2 N1) Squamous Cell Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a clinical laboratory improvement act (CLIA) approved laboratory.
• Patients must not have evidence of extensive or "matted/ fixed" pathologic adenopathy on preoperative imaging.
• The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT scan as appropriate, within 28 days before the first dose of therapy
• The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
• Criteria related to comparator drug or background therapy, if applicable: No prior radiation above the clavicles. Patients with a history of a curatively treated malignancy must be disease-free for at least two years prior to entry on study except for carcinoma in situ of cervix, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer
• Age \>= 18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol
• Histologically or cytologically confirmed p16+ HPV-driven OPSCC
• Availability of a representative tumor specimen for exploratory biomarker research
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (1500/GL) without granulocyte colony-stimulating factor support obtained within 14 days prior to initiation of study treatment

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• 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, with the following exceptions:
• 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 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
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Active tuberculosis
• History of leptomeningeal disease
• 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 recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX) are allowed.

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

atezolizumab; Neck Dissection; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Lymph Node Excision; Surgical Procedures, Operative; Otorhinolaryngologic Surgical Procedures; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Nabil F. Saba, MD, FACP

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: February 12, 2024
• Study Start: October 27, 2023
• Primary Completion (Estimated): December 16, 2026
• Study Completion (Estimated): December 16, 2026
• Last Updated: January 27, 2026

Record last verified: 2026-01

Locations

US (1)