Cancer, Cancer, Advanced, Cancer, Metastatic, Cancer of Head and Neck, Head and Neck Squamous Cell Carcinoma, Oral Cancer, Oropharyngeal Cancer, Oropharynx Cancer, Oropharynx Cancer, Metastatic, Oropharynx Cancer, Recurrent, Oropharynx Cancer, Stage III, Tumor, Tumor Metastasis, Tumor Neck, Tumor Recurrence
Conditions
Keywords
cancer, Head and Neck, Pembrolizumab, Cisplatin, Radiotherapy, Head and Neck Squamous Cell Carcinoma, p16+, immunotherapy, pd-1, chemotherapy, T1, T2, T3, N2, M0, T4, N3, N1
Brief summary
The purpose of this study is to compare any good or bad effects of using pembrolizumab (an experimental drug) and radiation therapy (RT), compared to using cisplatin chemotherapy and radiation therapy (RT) in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).
Detailed description
This study is a prospective, multi-institutional, open-label, randomized phase II trial that will evaluate the efficacy of concurrent and adjuvant pembrolizumab with radiation therapy (RT) versus RT plus cisplatin in intermediate/high-riskp16-positive locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The primary endpoint is progression-free survival (PFS).
Interventions
DRUGPembrolizumab
Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles
RADIATIONRadiation therapy
70 Gy in 33-35 fractions
DRUGCisplatin
100 mg/m2 Weeks 1, 4, and 7.
Sponsors
Merck Sharp & Dohme LLC
Loren Mell, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* p16-positive squamous cell carcinoma of the pharynx, larynx or oral cavity * High-Intermediate Risk Disease, defined as: * T1-T3 N2 M0 or T3 N1 M0 or any stage III (T4 or N3) p16+ squamous cell carcinoma of the oropharynx (AJCC 8th edition staging system) * T1-2 N1-3 M0 or T3-4 N0-3 M0 (stage III-IVB) p16+ squamous cell carcinoma of the hypopharynx or larynx * T1-2 N2-3 M0 or T3-4 N0-3 M0 (stage III-IVB) p16+ squamous cell carcinoma of the nasopharynx * Inoperable T4 N0-3 M0 (stage IVA-IVB) p16+ squamous cell carcinoma of the oral cavity * Measurable disease based on RECIST 1.1 * Adequate hematologic function within 28 days prior to registration * Adequate renal and hepatic function * Female subject of childbearing potential should have a negative pregnancy test * Female subjects of childbearing potential must agree to use an adequate method of contraception for the course of the study * Male subjects must agree to use an adequate method of contraception for the course of the study
Exclusion criteria
* Prior malignancy within the past 3 years (except non-melanomatous skin cancer and early stage treated prostate cancer); * Prior head and neck radiation, chemotherapy, or immunotherapy; * Prior oncologic (radical) surgery to the primary site; * Documented evidence of distant metastases; * Severe, active co-morbidity defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; * Transmural myocardial infarction within the last 6 months; * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration; * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. * Any medical or psychiatric illness, which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment; * Psychiatric/social situations that would limit compliance with study requirements * Hypersensitivity to pembrolizumab or any of its excipients. * Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Known history of, or any evidence of active, non-infectious pneumonitis. * Active infection requiring systemic therapy. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. * Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Has received a live vaccine within 30 days of planned start of study therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| progression-free survival (PFS) | 3 years | time from randomization to progression/relapse or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall survival | 3 years | time from randomization to death from any cause |
| Acute toxicity | 3 months | Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires |
| Late toxicity | 3 years | Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires |
| Patterns of failure | 3 years | Local and regional and distant recurrence of cancer and causes of death from competing events |
Other
| Measure | Time frame | Description |
|---|---|---|
| PD-L1 expression correlations | 3 years | compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression. |
Countries
United States
Outcome results
None listed