Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively

Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.

Pembrolizumab (immunotherapy)

* Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.

Therefore, the total prescription dose will be:

* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles

Quad-shot palliative radiotherapy

Study Nurse

Mercedes Porosnicu, MD

This is a single-arm, non-randomized pilot study to evaluate the efficacy and tolerability of combination quad-shot palliative radiotherapy with immunotherapy for advanced/recurrent/metastatic head and neck cancer.

Primary Objective: Measure the overall response rate for immunotherapy given with quad-shot radiotherapy.

Secondary Objective(s)

* Measure the response rate at the target lesion.
* Measure the response rate at non-target sites in patients with non-target sites.
* Evaluate the durability of response at the target lesion.
* Evaluate progression-free survival.
* Evaluate overall survival.
* Assess the tolerability of the combination of quad-shot radiotherapy with immunotherapy in order to assess the feasibility of this treatment regimen.

Exploratory Objective: Evaluate the effect of quad- shot administration on increasing the immune activation by treatment with pembrolizumab and investigate possible mechanisms.

OUTLINE: Patients receive standard of care pembrolizumab intravenously (IV) over 30 minutes every 3 weeks. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo quad-shot radiation therapy twice daily (BID) on 2 consecutive days between cycles 2-3 or 3-4, 6-7, and 11-12 of pembrolizumab treatment and in the last week of pembrolizumab treatment.

After completion of study treatment, patients are followed up at 1 and 2 months for adverse events monitoring. Patients will be followed until death for monitoring survival study endpoints. Frequency of visits will be established by the treating physician and will be done in person or over the phone.

Quad Shot Radiotherapy in Combination With Immune Checkpoint Inhibition

Quad-Shot Radiotherapy in Combination With Immune Checkpoint Inhibition for Advanced/Recurrent Head and Neck Cancer

Overall response will be measured according to RECIST 1.1 criteria to determine the percentage of participants with either a partial or complete response and the corresponding 95% Clopper-Pearson exact confidence interval. The best overall response is the best response recorded from the start of the treatment across all time points.

Response rate will be measured as the following:

Complete: Disappearance (or decrease to the point at which measurement is not possible) of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

Partial: At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase.

Stable Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase.

Response rate will be measured using RECIST 1.1:

Complete: Disappearance (or decrease to the point at which measurement is not possible) of all non-target lesions. All lymph nodes must be non-pathological in size (\< 10 mm short axis).

Partial: Non-complete response/Non-progressive disease: Persistence of 1 or more non-target lesion(s).

Progressive Disease: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Stable Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase.

For the duration of response, among participants investigators will estimate both the mean duration and the corresponding 95% confidence intervals for the mean and inter-quartile range for the median.

For the duration of response, among participants investigators will estimate the median duration and the corresponding 95% confidence intervals for the mean and inter-quartile range for the median.

For progression-free survival investigators will estimate Kaplan Meier survival curves and the median time to progression-free survival.

For time to event measure of overall survival investigators will estimate Kaplan Meier survival curves and the median time to overall survival.

Tolerability of intervention will be assessed using Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Event (PRO CTCAE). Investigators will estimate the percentage of patients with different adverse events using a 95% Clopper Pearson exact confidence level.

National Cancer Institute (NCI)

Wake Forest University Health Sciences

Neoplasm Metastasis

Fluorodeoxyglucose F18

Panitumumab

Patients receive panitumumab IV, 89Zr panitumumab IV, and undergo PET/CT on study

Zirconium Zr 89 Panitumumab

Positron Emission Tomography

Computed Tomography

Electronic Health Record Review

Vanderbilt-Ingram Services for Timely Access

Vanderbilt-Ingram Service for Timely Access

Michael Topf, MD

The goal of this phase I clinical trial is to evaluate the usefulness of an imaging test (zirconium Zr 89 panitumumab \[89Zr panitumumab\]) with positron emission tomography (PET)/computed tomography (CT) for diagnosing the spread of disease from where it first started (primary site) to other places in the body (metastasis) in patients with head and neck squamous cell carcinoma. Traditional PET/CT has a low positive predictive value for diagnosing metastatic disease in head and neck cancer. 89Zr panitumumab is an investigational imaging agent that contains radiolabeled anti-EGFR antibody which is overexpressed in head and neck cancer. The main question this study aims to answer is the sensitivity and specificity of 89Zr panitumumab for the detection of indeterminate metastatic lesions in head and neck cancer.

Participants will receive 89Zr panitumumab infusion and undergo 89Zr panitumumab PET/CT 1 to 5 days after infusion. Participants will otherwise receive standard of care evaluation and treatment for their indeterminate lesions.

Researchers will compare the 89Zr panitumumab to standard of care imaging modalities (magnetic resonance imaging (MRI), CT, and/or PET/CT).

PRIMARY OBJECTIVE:

- Determine the sensitivity and specificity of zirconium Zr 89 panitumumab (89Zrpanitumumab) for the detection of indeterminate metastatic lesions in head and neck squamous cell carcinoma.

SECONDARY OBJECTIVE:

- Compare sensitivity and specificity of standard of care imaging modalities (magnetic resonance imaging \[MRI\], CT and/or fludeoxyglucose F-18 \[18F\]-PET/CT) to 89Zr-panitumumab-PET/CT for detection of indeterminate metastatic lesions in head and neck squamous cell carcinoma.

EXPLORATORY OBJECTIVE:

- Determine rate of intervention (e.g., biopsy or other invasive procedures) versus (vs) non-intervention (e.g., serial imaging, observation) by treatment team in subjects with indeterminate metastatic lesions on standard of care imaging.

OUTLINE:

Patients receive panitumumab intravenously (IV), 89Zr panitumumab IV, and undergo PET/CT on study.

(89Zr Panitumumab) With PET/CT for Diagnosing Metastases in Patients With Head and Neck Squamous Cell Carcinoma

Study Evaluating 89Zr Panitumumab for Assessment of Indeterminate Metastatic Lesions on 18F-FDG-PET/CT in Head and Neck Squamous Cell Carcinoma

The total number of head and neck squamous cell carcinoma lesions accurately detected by 89Zr-panitumumab using positron emission tomography (PET)/computed tomography (CT) imaging (test) will be compared with lesions identified as positive during the 36 +/- 6 month follow-up period (gold standard). Significance will be assessed at an alpha level of 0.05 and, to assess uncertainty, 95% confidence intervals will be provided for all estimates.

The total number of head and neck squamous cell carcinoma lesions accurately detected by 89Zr-panitumumab using PET/CT imaging (test) will be compared with lesions identified as positive during the 36 +/- 6 month follow-up period (gold standard). Significance will be assessed at an alpha level of 0.05 and, to assess uncertainty, 95% confidence intervals will be provided for all estimates.

The sensitivity of 89Zr-panitumumab will be compared to the sensitivity of standard of care imaging modalities, including magnetic resonance imaging (MRI), CT, and/or fludeoxyglucose F-18 (18F-FDG) PET/CT. Will use the matched pair Durkalski's test, accounting for the cluster-correlation within subjects, for the sensitivity comparisons.

The specificity of 89Zr-panitumumab will be compared to the specificity of standard of care imaging modalities, including MRI, CT, and/or 18F-FDG PET/CT. Will use the matched pair Durkalski's test, accounting for the cluster-correlation within subjects, for the specificity comparisons.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Quad Shot Radiotherapy in Combination With Immune Checkpoint Inhibition	NCT04454489	Advanced Head a... Recurrent Head ... Metastatic Head... Stage III Cutan... Locally Advance... Stage IV Cutane...	Pembrolizumab (... Quad-shot palli...	18 Years -	Wake Forest University Health Sciences
(89Zr Panitumumab) With PET/CT for Diagnosing Metastases in Patients With Head and Neck Squamous Cell Carcinoma	NCT05747625	Head and Neck S... Metastatic Head... Stage IV Cutane...	Panitumumab Zirconium Zr 89... Positron Emissi... Computed Tomogr... Electronic Heal...	19 Years -	Vanderbilt-Ingram Cancer Center
Quad Shot Radiotherapy in Combination With Immune Checkpoint Inhibition	NCT04454489	Advanced Head a... Recurrent Head ... Metastatic Head... Stage III Cutan... Locally Advance... Stage IV Cutane...	Pembrolizumab (... Quad-shot palli...	18 Years -	Wake Forest University Health Sciences

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