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
- 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.
- Advanced, recurrent or metastatic head and neck squamous cell carcinoma, as defined by
clinical or pathological diagnosis of any of the following:
- Locally advanced head and neck squamous cell carcinoma not suitable for curative local
- Locally recurrent head and neck squamous cell carcinoma not suitable for curative
local treatment within or outside a previously irradiated tissue.
- Metastatic head and neck squamous cell carcinoma.
- Target site in the head and neck region amenable to quad-shot palliative radiotherapy,
for which palliative radiotherapy is recommended, as determined by the treating
- Age 18 years or greater at time of registration.
- ECOG Performance Status of 0-2.
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
- Ability to understand and the willingness to sign an IRB-approved informed consent
document (either directly or via a legally authorized representative).
- Willingness to provide blood and saliva samples for exploratory research purposes.
- Organ and Marrow Function as defined below: Absolute neutrophil count (ANC) ≥ 1.5 x
109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, serum bilirubin ≤ 1.5 x
ULN (institutional upper limit of normal), AST and ALT ≤ 2.5 x ULN (institutional
upper limit of normal), serum creatinine CL>40 mL/min by the Cockcroft-Gault formula
(Cockcroft and Gault 1976) or by 24-hour urine collection for determination of
MALES: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) (divided by) 72 x serum
FEMALES: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 (divided by) 72 x serum
- Radiation therapy to the head and neck region within 30 days of registration.
- Prior radiotherapy to the head and neck that precludes safe delivery of study
radiotherapy, as determined by the treating radiation oncologist.
- Active medical conditions that are contraindications to study radiotherapy (i.e.
scleroderma), as determined by the treating radiation oncologist.
- Pregnant or lactating women are excluded from this study because radiotherapy is
contraindicated in pregnancy and because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with
- Participation in another clinical study with an investigational product during the
last 3 months.
- Any previous treatment with a PD1 or PD-L1 inhibitor.
- Any anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted
therapy, biologic therapy, tumor embolization, monoclonal antibodies, other
investigational agent) within the last 30 days.
- Mean QT interval corrected for heart rate (QTc) ≥470 ms except for patients with
pacemaker who have a paced ventricular rhythm.
- Current or prior use of immunosuppressive medication within 30 days, with exceptions
of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological
doses, which are not to exceed 10 mg/day of prednisone, or an equivalent
- Any unresolved toxicity (>CTCAE grade > 2) from previous anti-cancer therapy. Subjects
with irreversible toxicity that is not reasonably expected to be exacerbated by the
investigational product may be included (e.g., hearing loss, peripherally neuropathy).
- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE >Grade 1.
- Active or prior documented autoimmune disease within the past 2 years, NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
- History of primary immunodeficiency.
- History of allogeneic organ transplant.
- History of hypersensitivity to any excipient in pembrolizumab.
- History of pneumonitis or interstitial lung disease.
- Subjects with uncontrolled seizures.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, uncontrolled cardiac arrhythmia, active peptic ulcer disease or
gastritis, active bleeding diatheses, evidence of acute or chronic hepatitis B,
hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social
situations that would limit compliance with study requirements or compromise the
ability of the subject to give written informed consent.
- Known history of active tuberculosis.
- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving pembrolizumab.
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results.