Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Control-radiotherapy/cisplatin Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent cisplatin 100 mg/m2 every 3 weeks for 3 cycles (7 weeks) |
Radiation: Radiation therapy
70 Gy in 33-35 fractions
Other Names:
Drug: Cisplatin
100 mg/m2 Weeks 1, 4, and 7.
Other Names:
|
| Experimental: Experimental-Radiotherapy/pembrolizumab Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent and adjuvant pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles |
Drug: Pembrolizumab
Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles
Other Names:
Radiation: Radiation therapy
70 Gy in 33-35 fractions
Other Names:
|
Outcome Measures
Primary Outcome Measures
- progression-free survival (PFS) [3 years]
time from randomization to progression/relapse or death from any cause.
Secondary Outcome Measures
- 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 Outcome Measures
- PD-L1 expression correlations [3 years]
compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression.
Eligibility Criteria
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.
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Any medical or psychiatric illness, which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment;
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Psychiatric/social situations that would limit compliance with study requirements
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Hypersensitivity to pembrolizumab or any of its excipients.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Arizona Cancer Center | Tucson | Arizona | United States | 85719 |
| 2 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
| 3 | Yale Cancer Center | New Haven | Connecticut | United States | 06520 |
| 4 | H. Lee Moffitt Cancer Center & Research Facility | Tampa | Florida | United States | 33612 |
| 5 | Washington University School of Medicine, Siteman Cancer Center | Saint Louis | Missouri | United States | 63110 |
| 6 | University of Cincinnati Medical Center | Cincinnati | Ohio | United States | 45219 |
| 7 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Loren Mell, MD
- Merck Sharp & Dohme LLC
Investigators
- Principal Investigator: Loren Mell, MD, University of California, San Diego
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 170862