Summary

This randomized phase II trial studies how well pembrolizumab works in treating patients with stage III-IVB head and neck squamous cell cancer that has come back. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Objectives

PRIMARY OBJECTIVE:
I. Progression free survival (PFS).

SECONDARY OBJECTIVES:
I. PFS, in gene expression profile (GEP) positive patients.
II. PFS, in PD-L1 > 10% positive patients.
III. Overall survival (OS), in the overall patient population, and in gene expression signature (GES) positive or PD-L1 positive (>= 10%) patients.

EXPLORATORY OBJECTIVES:
I. Gene expression profile, head and neck cancer (HNC) intrinsic subtype determination, and broader ribonucleic acid sequencing (RNAseq) analysis: correlation with recurrence.
II. Gene expression profile evaluation in blood at baseline and 3-4 week after pembrolizumab treatment and correlation with recurrence.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive placebo IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 12-16 weeks for 2 years.

Eligibility

1. Patients must have histologically confirmed head and neck cancer (squamous cell histology), and may be poorly differentiated, stages IVA, IVB, and select cases of stage III or any stage that meets criterion * Human papilloma virus (HPV) status is required prior to randomization for oropharyngeal primary tumors, other anatomic sites will be classified as HPV- unless requested per the treating physician * Epstein Barr virus (EBV) status is required prior to randomization for nasopharyngeal primary tumors, other anatomic sites will be classified as HPV- unless requested per the treating physician
2. Completed curative intent therapy, without additional standard of care curative intent therapy feasible within 20 weeks prior to study enrollment
3. After prior curative intent treatment for HNC have estimated risk of recurrence >= 40-50% and fall into one of the below categories (A, OR B, OR C, OR D, OR E, OR F); while exact estimation of the risk of recurrence can be difficult the following categories will be included reflecting patients at substantial risk for tumor recurrence or already with early evidence of recurrence: * A: Any of the below HNC patients are eligible for treatment on this protocol AFTER completion of curative intent therapy: ** HPV(-) HNC: N2C, N3, bulky N2B disease (>= 5 cm LN/tumor conglomerate) ** HPV(+) HNC: N2C, N3, AND >= 10 pack years of tobacco use ** HPV(+) HNC with multilevel nodal involvement, AND bulky N2B disease (>= 5 cm LN/tumor conglomerate), AND >= 10 pack years of tobacco use ** EBV(+) nasopharyngeal carcinoma (NPC) may be eligible if other criteria under A, or alternative criteria B, or C, or D, or E are met ** HNC with supraclavicular or mediastinal nodal involvement (either HPV+/- or EBV+/-) at the time of curative intent treatment and were treated as part of curative intent therapy (e.g. inclusion in the radiation field) ** Residual mass in area of prior tumor that on biopsy does not show residual tumor, is equivocal/not highly-suspicious on imaging (e.g. positron emission tomography/ computed tomography/magnetic resonance imaging [PET/CT/MRI]), but remains of concern, requires close follow-up AND is not resected/amenable to resection OR immediate palliative treatment ** Non-responders to induction chemotherapy (progressive disease [PD] on induction, or lack of tumor shrinkage (< 15% per Response Evaluation Criteria in Solid Tumors [RECIST]) ** Interrupted treatment course or lower than intended radiation dose – i.e. interruption of radiation by >= 3 weeks (cumulative), or delivery of =< 50 Gy as part of a radiation based treatment (that was NOT a de-escalation approach) * B: Patient treated with salvage treatment (i.e. salvage surgery or re-irradiation) for residual or recurrent tumor after prior radiation based therapy (either HPV+ or HPV- or EBV+) AND not a candidate for additional curative intent therapy (for various reasons including poor performance status, comorbidities, refusal of patient, prior radiation or re-irradiation, etc); positive margins or residual tumor may still be acceptable); patients should also not be appropriate for systemic palliative therapy (e.g. in the case of overt disease) * C: Mx or indeterminate distant lesions that are not appropriate for either local radiation/stereotactic body radiation therapy (SBRT) treatment and also not appropriate for initiation of palliative system therapy (e.g. in the setting of overt metastatic disease); such lesions should be negative/equivocal by PET imaging and if amenable negative by biopsy, but remain of concern and require close follow-up * D: Oligometastatic disease treated with SBRT or other curative-intent therapy (e.g. surgery or radiofrequency ablation (RFA), etc) for oligometastatic disease * E: Microscopic or very low volume residual tumor after surgery or radiation based treatment (including salvage treatment or SBRT for oligometastatic disease), AND not a candidate for either additional curative intent therapy (for various reasons including feasibility, poor performance status, comorbidities, refusal of patient, prior radiation or re-irradiation, etc) AND also not a candidate for systemic palliative therapy (for various reasons including microscopic/non-[RECIST] measurable low volume disease); very low volume disease is defined as non-RECIST measurable) * F: Patients with multiple recurrences or multiple primaries: specifically patients who had malignant or pre-malignant tumors/changes (with severe dysplasia present), who have undergone surgery >= 2 times, and currently do not have an indication for additional (adjuvant) treatment such as radiation, or surgery, or other treatment; this may include multiple recurrences/incidences of early stage tumors or premalignant lesions, however at least one lesion needs to show squamous cell carcinoma on pathology * There may be additional scenarios for patients that are considered very high risk for disease recurrence and not appropriate for either curative or standard of care palliative therapy; such patients can be considered for enrollment after discussion and approval by the lead principal investigator (PI) and/or co-PI
4. Availability of tumor tissue (>= 10 slides) for PD-L1, gene expression profiling (GEP), and additional testing
5. Be willing and able to provide written informed consent/assent for the trial
6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale; an ECOG performance status of 2 is acceptable if the patient was ECOG 0/1 prior to curative intent therapy and is in the midst of recovery from curative intent therapy
7. Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 10 days of treatment initiation)
8. Platelets >= 100,000/mcL (performed within 10 days of treatment initiation)
9. Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 10 days of treatment initiation)
10. Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance [CrCl]) =< 2.0 x upper limit of normal (ULN) OR >= 40 mL/min for subject with creatinine levels > 2.0 x institutional ULN (performed within 10 days of treatment initiation)
11. Serum total bilirubin =< 2 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 2 ULN (performed within 10 days of treatment initiation)
12. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (performed within 10 days of treatment initiation)
13. International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
14. Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
15. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
16. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
17. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Treatment Sites in Georgia