Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery. Beginning 6 weeks after surgery, patients with residual disease undergo standard of care radiation therapy and receive atezolizumab IV over 30-60 minutes on day 1. Treatment with atezolizumab repeats every 21 days for up to 15 cycles in the absence of disease progression and unacceptable toxicity.

Radiation Therapy

Therapeutic Conventional Surgery

Arnaud Bewley

This phase II trial tests whether atezolizumab works to shrink tumors before surgery in patients with head and neck squamous cell cancer with an unknown or historic primary site that has spread to other places in the lymph nodes (regionally metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab before surgery may reduce the size of the tumor.

PRIMARY OBJECTIVE:I. Evaluate the rate of pathologic complete response (pCR) at the time of surgery following neo-adjuvant atezolizumab in patients with regionally metastatic head and neck cutaneous squamous cell carcinoma (HNSCCC).

SECONDARY OBJECTIVES:I. Further characterize the oncologic response to neo-adjuvant atezolizumab and adjuvant atezolizumab in combination with radiation therapy in patients with regionally metastatic HNSCCC:Ia. Determine the rate of major pathologic response (mPR) at the time of surgery.Ib. Evaluate the 2-year event free survival (EFS) after completion of adjuvant therapy.

II. Investigate the utility of conventional imaging and novel biomarkers in predicting and assessing response to neoadjuvant atezolizumab therapy.IIa. Investigate associations between pre-treatment tumor fludeoxyglucose F-18 (FDG) avidity and response to neoadjuvant immunotherapy.IIb. Evaluate the ability of fine-cut contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the head and neck to assess response to neoadjuvant immunotherapy prior to surgery.IIc. Evaluate the capabilities of serial liquid biopsy analysis of tumor-associated exosomes to predict neoadjuvant immunotherapy response.

III. Evaluate the safety and tolerability of anti-PD-L1 with atezolizumab neo-adjuvant therapy in resectable regional metastatic HNCSCC.IIIa. Quantify toxicity (adverse events) determined by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.

OUTLINE:Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery. Beginning 6 weeks after surgery, patients with residual disease undergo standard of care radiation therapy and receive atezolizumab IV over 30-60 minutes on day 1. Treatment with atezolizumab repeats every 21 days for up to 15 cycles in the absence of disease progression and unacceptable toxicity.After completion of study treatment, patients are followed up every 3 months for up to 3 years.

Atezolizumab Before Surgery for the Treatment of Regionally Metastatic Head and Neck Squamous Cell Cancer With an Unknown or Historic Primary Site

Neo-Adjuvant Atezolizumab Prior to Definitive Surgical Resection of Regionally Metastatic Head &Amp; Neck Cutaneous Squamous Cell Carcinoma With an Unknown or Historic Primary Site: A Window Trial

pCR is defined as having no residual invasive squamous cell carcinoma within the primary tumor and all resected lymph nodes as assessed by the pathologist at the time of primary resection. The rate of pCR is defined as the proportion of patients demonstrating pCR.

mPR is defined as having =\< 10% residual invasive squamous cell carcinoma within the primary tumor and all resected lymph nodes as assessed by the pathologist at the time of primary resection. The rate of mPR is defined as the proportion of patients demonstrating mPR.

A non-parametric Kaplan-Meier (KM) method will be used to estimate the 2-year EFS curve. Participants who do not experience recurrence or disease progression at the time of their last follow-up will be censored. Recurrence, all-cause death and disease-specific death will be likewise examined using the KM method to determine estimates of 2-yr disease-free survival, overall survival and disease-specific survival.

FDG avidity of nodal sites will be quantified according to standardized uptake value (SUV). The SUV is the ratio of the image derived radioactivity concentration of the lesion of interest and the whole body concentration of the injected radioactivity. Standard of care staging positron emission tomography (PET)/computed tomography (CT) will be performed prior to initiation of treatment and as a post-treatment scan 3 months after completion. The association of the SUV of the regionally metastatic focus of disease to the pathologic response to neoadjuvant therapy at the time of surgery will be examined. A t-test (or nonparametric counterpart) and multiple regression will be used to compare mean SUV between patients who experience cPR to the mean SUV of those with residual disease after neoadjuvant therapy, where the latter will adjust patient characteristics and potential confounders. In addition, the mean SUV of additional sites of regionally metastatic disease will be studied.

Measured by CT or magnetic resonance imaging (MRI) of the head and neck per immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria.

Determined by Common Terminology Criteria for Adverse Events version 5. Safety and tolerability will be assessed by clinical review of all relevant parameters including adverse events, laboratory tests, and vital signs. Descriptive statistics will be provided for adverse events.

National Cancer Institute (NCI)

Genentech, Inc.

Arnaud Bewley, MD

Principal Investigator

Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery. Beginning 6 weeks after surgery, patients with residual disease undergo standard of care radiation therapy and receive atezolizumab IV over 30-60 minutes on day 1. Treatment with atezolizumab repeats every 21 days for up to 15 cycles in the absence of disease progression and unacceptable toxicity.

Atezolizumab: Given IV

Radiation Therapy: Undergo radiation therapy

Therapeutic Conventional Surgery: Undergo surgery

Treatment (Atezolizumab, Surgery, Radiation Therapy)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

One participant was enrolled in study prior to termination. Enrollment in the clinical trial did not reach the target number of participants needed to achieve target power and was insufficient to produce statistically reliable results.

Pathologic Complete Response (pCR)

Major Pathologic Response (mPR)

Number of Participants With Recurrence or Disease Progression

Baseline SUV

Month 3 SUV

Standardized Uptake Value (SUV) of Primary Lesion Assessed at Baseline and 3 Months After Completion of Treatment

Number of Participants With Overall Response

Plasma exosome level was not measured as the study was terminated early due to low accrual and only 1 evaluable participant was enrolled.

Plasma Exosome Levels

Number of Adverse Events

Overall Study

Symptoms and General Pathology

Recurrence

Cemiplimab

Patients receive cemiplimab IV over 30 minutes every 3 weeks. Cycles repeat every 3 weeks for up to 6 weeks with or without radiation therapy at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity.

Neil D Gross, MD

Neil D. Gross

This phase II trial studies how well cemiplimab works before surgery in treating patients with stage II-IV head and neck cutaneous squamous cell cancer that has come back (recurrent) and can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. To determine the overall response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria to neoadjuvant cemiplimab (REGN2810) in patients with stage II-IV cutaneous squamous cell carcinoma (cSCC) of the head and neck who are planned for definitive local surgery with or without radiation.

SECONDARY OBJECTIVES:

I. To determine the pathologic response rate to neoadjuvant REGN2810 in patients with stage II-IV cSCC of the head and neck.

II. To determine the safety and tolerability of neoadjuvant REGN2810 in patients with stage II-IV cSCC of the head and neck who are planned for definitive local surgery and radiation.

III. To estimate the 2-year disease-specific (DSS), disease-free (DFS) and overall survival (OS) compared to historical controls.

IV. To determine the time to recurrence and patterns of failure.

V. To evaluate the effects of neoadjuvant REGN2810 on the expression of PD-1 and potential related immune regulating targets in cSCC of the head and neck.

OUTLINE:

Patients receive cemiplimab intravenously (IV) over 30 minutes every 3 weeks. Cycles repeat every 3 weeks for up to 6 weeks with or without radiation therapy at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then periodically for up to 5 years.

Cemiplimab in Treating Patients With Recurrent and Resectable Stage II-IV Head and Neck Cutaneous Squamous Cell Cancer Before Surgery

Phase II Study of REGN2810 Prior to Surgery in Patients With Stage II-IV Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck

Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

Summary statistics will be provided for continuous variables.

Frequency tables will be used to summarize categorical variables.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Atezolizumab Before Surgery for the Treatment of Regionally Metastatic Head and Neck Squamous Cell Cancer With an Unknown or Historic Primary Site	NCT05110781	Locally Advance... Resectable Cuta... Stage III Cutan...	Atezolizumab Radiation Thera... Therapeutic Con...	18 Years -	University of California, Davis
Cemiplimab in Treating Patients With Recurrent and Resectable Stage II-IV Head and Neck Cutaneous Squamous Cell Cancer Before Surgery	NCT03565783	Recurrent Cutan... Resectable Cuta... Stage II Cutane... Stage III Cutan... Stage IV Cutane...	Cemiplimab	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for resectable cutaneous squamous cell carcinoma of the head and neck