Clinical trial NCT03383094: Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
Official title: Phase II Randomized Trial of Radiotherapy With Concurrent and Adjuvant Pembrolizumab (Keytruda®) Versus Concurrent Chemotherapy in Patients With Advanced/Intermediate-Risk p16+ Head and Neck Squamous Cell Carcinoma (KEYCHAIN)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Cancer
Cancer of Head and Neck
Cancer, Advanced
Cancer, Metastatic
Tumor
Tumor Recurrence
Tumor Neck
Tumor Metastasis
Oral Cancer
Oropharyngeal Cancer
Oropharynx Cancer
Oropharynx Cancer, Stage III
Oropharynx Cancer, Recurrent
Oropharynx Cancer, Metastatic
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
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-12-26
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: progression-free survival (PFS)
timeFrame: 3 years
Secondary outcomes:
measure: overall survival
timeFrame: 3 years
measure: Acute toxicity
timeFrame: 3 months
measure: Late toxicity
timeFrame: 3 years
measure: Patterns of failure
timeFrame: 3 years
Other outcomes:
measure: PD-L1 expression correlations
timeFrame: 3 years
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Facility
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Siteman Cancer Center
state: Missouri
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: University of California, San Diego
name: Loren Mell, MD
role: PRINCIPAL_INVESTIGATOR
References: