Comparing immunotherapy and radiation to chemotherapy and radiation for head and neck cancer

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)

This study is testing if a new immunotherapy drug combined with radiation can help people with head and neck cancer live longer without their cancer getting worse compared to the usual chemotherapy and radiation treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 114 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Diego (Academic / other)
• Drugs / interventions: pembrolizumab, chemotherapy, immunotherapy, radiation
• Locations: 7 sites (Tucson, Arizona and 6 other locations)
• Trial ID: NCT03383094 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of pembrolizumab, an experimental immunotherapy drug, combined with radiation therapy, against the standard treatment of cisplatin chemotherapy and radiation therapy in patients with intermediate to high-risk head and neck squamous cell carcinoma. It is a multi-institutional, open-label, randomized phase II trial focusing on progression-free survival as the primary endpoint. The trial aims to determine if the immunotherapy approach can provide better outcomes than traditional chemotherapy.

Who should consider this trial

Good fit: Ideal candidates are patients with p16-positive squamous cell carcinoma of the pharynx, larynx, or oral cavity who are classified as high-intermediate risk.

Not a fit: Patients with inoperable or non-p16-positive head and neck squamous cell carcinoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a more effective treatment option for patients with head and neck cancer, potentially improving survival rates.

How similar studies have performed: Other studies have shown promising results with immunotherapy approaches in cancer treatment, suggesting potential success for this novel combination.

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.

Where this trial is running

Tucson, Arizona and 6 other locations

• University of Arizona Cancer Center — Tucson, Arizona, United States (Recruiting)
• UC San Diego Moores Cancer Center — La Jolla, California, United States (Recruiting)
• Yale Cancer Center — New Haven, Connecticut, United States (Recruiting)
• H. Lee Moffitt Cancer Center & Research Facility — Tampa, Florida, United States (Recruiting)
• Washington University School of Medicine, Siteman Cancer Center — Saint Louis, Missouri, United States (Recruiting)
• University of Cincinnati Medical Center — Cincinnati, Ohio, United States (Recruiting)
• Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Loren Mell, MD — University of California, San Diego
• Study coordinator: Loren Mell, MD

Conditions Head and Neck Squamous Cell Carcinoma; Cancer; Cancer of Head and Neck; Cancer, Advanced; Cancer, Metastatic; Tumor; Tumor Recurrence; Tumor Neck