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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
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 iii cutaneous squamous cell carcinoma of the head and neck