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

Rare Diseases

Laryngeal Cancer

Hypopharyngeal Cancer

Cisplatin

Patients who already underwent surgical resection undergo IMPT for 18 sessions (Monday-Friday) over 24 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care.

Patients undergo surgical resection and then IMPT for 15 sessions (Monday-Friday) over 19 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care.

Intensity-Modulated Proton Therapy

Quality-of-Life Assessment

Questionnaire Administration

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Biospecimen Collection

Clinical Trials Referral Office

Lisa A. McGee, M.D.

Scott C. Lester, M.D.

This clinical trial tests whether intensity modulated proton therapy after surgery works to shrink tumors in patients with head and neck cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors.

PRIMARY OBJECTIVE:

I. The primary goal is to evaluate the local-regional control among subjects in both arms at 2 years after study registration.

SECONDARY OBJECTIVES:

I. To determine overall survival progression free survival local, regional, distant recurrence risks, and infield and outfield recurrence in the trial at 2 years after study registration.

II. To determine the rate and duration of grade 3+ acute adverse events from treatment start to 30 days after radiation completion date).

III. To determine the incidence of secondary acute effects attributable to radiotherapy (e.g. percutaneous endoscopic gastrostomy \[PEG\] tube placement, duration and dose of narcotic analgesia required, weight loss, and hospitalization days).

IV. To determine the impact of treatment on patient reported quality of life. V. To objectively quantify the severity of oral mucositis during and following radiotherapy.

EXPLORATORY OBJECTIVES:

I. To estimate direct and indirect costs of the study regimen and compare these with standard of care treatment techniques.

II. To correlate histopathologic, molecular, and tumor genetic/epigenetic alterations with clinical outcomes.

III. To correlate circulating biomarkers (microribonucleic acid \[miRNA\], circulating tumor deoxyribonucleic acid \[ctDNA\]) with clinical outcomes.

IV. To determine adverse events and patient reported outcomes related to abbreviated concomitant chemotherapy.

V. To determine incidence and severity of late effects attributable to radiotherapy at 1-3 years after treatment.

VI. To qualitatively evaluate patient beliefs regarding tradeoffs of cancer control, treatment time, cost, acute side effects, and late side effects.

VII. To determine cancer out comes, adverse events, and patient reported outcomes and compare across head and neck subsites, between those aged 65 to those age \< 65 at date of enrollment, between male and female, and in the adjuvant population between time to total package completion (\< 9 weeks vs weeks, surgery day 0) and by treatment with and without chemotherapy.

VIII. To evaluate the predictive relationship of linear energy transfer (LET) weighted modeling using an relative biologic enhancement (RBE) based model and RBE independent model with grade 3+ acute and late toxicity.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM A: Patients who already underwent surgical resection undergo intensity modulated proton therapy (IMPT) for 18 sessions (Monday-Friday) over 24 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin intravenously (IV) over 1-2 hours per standard of care. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT or PET/MRI during screening and follow-up. Patients may optionally undergo blood sample collection throughout the trial.

ARM B: Patients undergo surgical resection and then IMPT for 15 sessions (Monday-Friday) over 19 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care. Patients undergo CT or MRI and PET/CT or PET/MRI during screening and follow-up. Patients may optionally undergo blood sample collection throughout the trial.

After completion of study treatment, patients are followed up within 21 days, every 3 months for 2 years, and then every 6-12 months for 5-10 years.

HEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers

The 2-year LRF rate will be estimated by counting the number of patients with a local or regional failure and dividing by the total number of eligible patients.

The maximum grade for each type of acute adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

The maximum grade for each type of late adverse event will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

The electronic health record will be reviewed for treatments related to secondary acute effects such as PEG tube placement, duration and dose of narcotic analgesia required, weight loss, and hospitalization days.

MD Anderson Dysphagia Inventory (MDADI) will be utilized to assess patient reported quality-of-life and financial burden. Changes from baseline to end of therapy as well as repeated measures mixed models will be utilized to assess effect of treatment. The QOL measurements will be summarized at each time point as mean +/- standard deviation and median (minimum value, maximum value). Changes in the QOL measurements from baseline will be determined at each follow-up measurement. These will be displayed as spaghetti plots. The assessment of the changes at each time point will be done with a paired t-test or Wilcoxon signed rank test, whichever is appropriate. Scale of 0 being least and 10 being greatest effect.

European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L) will be utilized to assess patient reported quality-of-life and financial burden. Changes from baseline to end of therapy as well as repeated measures mixed models will be utilized to assess effect of treatment. The QOL measurements will be summarized at each time point as mean +/- standard deviation and median (minimum value, maximum value). Changes in the QOL measurements from baseline will be determined at each follow-up measurement. These will be displayed as spaghetti plots. The assessment of the changes at each time point will be done with a paired t-test or Wilcoxon signed rank test, whichever is appropriate. Scale of 0 being least and 10 being greatest effect.

Oral Mucositis Weekly Questionnaire (OMWQ-HN) will be utilized to assess patient reported quality-of-life and financial burden. Changes from baseline to end of therapy as well as repeated measures mixed models will be utilized to assess effect of treatment. The QOL measurements will be summarized at each time point as mean +/- standard deviation and median (minimum value, maximum value). Changes in the QOL measurements from baseline will be determined at each follow-up measurement. These will be displayed as spaghetti plots. The assessment of the changes at each time point will be done with a paired t-test or Wilcoxon signed rank test, whichever is appropriate. Scale of 0 being least and 10 being greatest effect.

The regional head and neck cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.). The competing risks will be local/distant head and neck cancer recurrence and death.

The local head and neck cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.). The competing risks will be regional/distant head and neck cancer recurrence and death.

The distant head and neck cancer recurrence cumulative incidence will be estimated using a competing risks method (Gooley et al.). The competing risks will be local/regional head and neck cancer recurrence and death.

The DFS will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals.

The OS will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals.

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
HEADLIGHT: Hypofractionated Proton Therapy for Head and Neck Cancers	NCT05075980	Head and Neck C... Head and Neck C... Hypopharyngeal ... Laryngeal Carci... Metastatic Mali... Nasal Cavity Ca... Oral Cavity Car... Oropharyngeal C... Paranasal Sinus... Salivary Gland ... Cutaneous Squam... Locally Advance...	Cisplatin Intensity-Modul... Quality-of-Life... Questionnaire A... Computed Tomogr... Magnetic Resona... Positron Emissi... Biospecimen Col...	18 Years -	Mayo Clinic

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