Head and Neck Cancer
Conditions
Brief summary
The purpose of this research study is to test the safety and the benefit of adding pembrolizumab (a therapy that activates the immune system to fight cancer) to standard of care treatment for head and neck cancer. The standard of care treatment will include surgery followed by radiation for 6 weeks. Some patients may also receive cisplatin as standard of care once a week for 6 weeks if the cancer is found to be "high risk". High risk includes cancer that was not completely removed (positive margins) or cancer that has invaded through the outer lining of your lymph nodes.
Interventions
DRUGPembrolizumab
Pembrolizumab administered one week prior to surgery and then every three weeks in the adjuvant setting for a total of 7 doses.
PROCEDURESurgery
gross total surgical resection
RADIATIONRadiation Therapy
60-66 Gy over 6 weeks
DRUGCisplatin
Weekly during radiation therapy for 6 doses only for patients with high risk pathological features
Sponsors
Trisha Wise-Draper
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients eligible for resection with one or more of the following 1. Any T stage with ≥ N2 disease; 2. T4 disease, any N stage; 3. T3 Oral Cavity, any N stage; or 4. Clinical evidence of extra-capsular extension on scans. * Must be willing to undergo definitive resection with neck dissection. * Performance status 0 or 1 on Eastern Cooperative Oncology Group Performance Scale. * Adequate labs * Appropriate staging imaging.
Exclusion criteria
* Diagnosis of immunodeficiency or receiving systemic steroid therapy or immunosuppressive therapy within 7 days prior to planned first dose of trial treatment. * Nasopharyngeal or sinonasal carcinoma * Confirmed metastatic disease * Human Papillomavirus (HPV)+ disease of the oropharynx * Known history of active tuberculosis (TB), autoimmune disease, pneumonitis, infection, HIV, Hepatitis B, or Hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Related Adverse Effects | All adverse events were recorded from the time the consent form is signed through 30 days following cessation of treatment. Any AE related to study drug after 30 days post treatment, subjects were followed until resolution. | Number of participants with treatment related adverse effects as assessed using CTCAE v4.0 of pembrolizumab when combined with radiation alone and chemoradiation. Compared as percentage of grade 3 and 4 adverse events with historical control percentages. |
| Disease Free Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation | 1 year | • High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins. |
| Disease Free Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation | 1 year | • Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Immune Response to Pembrolizumab as Defined by PD-L1 CPS in the Baseline Tumor Tissue | 1 week between receiving a pre-surgery dose of pembrolizumab and surgery when the biopsy was taken | Change in distribution of the tumor immune microenvironment after Pembrolizumab administration in tumor biopsy tissue using markers of T cells and T cell activation using PD-L1 CPS. PD-L1 CPS is defined as the PD-L1 combined positive score. PD-L1 CPS is defined as Combined positivity score (CPS) was calculated by summing the numbers of PD-L1-positive tumor cells and immune cells and dividing by the total number of viable tumor cells. Additionally, PD-L1 is a protein that helps the body immune system remain in control. The denominator in this case is 72 subjects that were evaluable. Evaluable means the subject had a pre-surgery pembrolizumab and a biopsy taken. The numerators are explained below. |
| Overall Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation | 1 year | • Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins |
| Overall Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation | 1 year | • High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTrisha Wise-Draper, MD, PhD
University of Cincinnati
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Pembrolizumab in combination with standard of care surgery followed by radiation therapy with or without cisplatin
Pembrolizumab: Pembrolizumab administered one week prior to surgery and then every three weeks in the adjuvant setting for a total of 7 doses.
Surgery: gross total surgical resection
Radiation Therapy: 60-66 Gy over 6 weeks
Cisplatin: Weekly during radiation therapy for 6 doses only for patients with high risk pathological features | 92 |
| Total | 92 |
Baseline characteristics
| Characteristic | Pembrolizumab |
|---|---|
| Age, Continuous | 59 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 87 Participants |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 20 / 96 |
| other Total, other adverse events | 92 / 96 |
| serious Total, serious adverse events | 43 / 96 |
Outcome results
Primary
Disease Free Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation
• High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins.
Time frame: 1 year
Population: • High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Disease Free Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation | 66 percentage of high risk participants |
Primary
Disease Free Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation
• Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins.
Time frame: 1 year
Population: • Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Disease Free Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation | 96 percentage of intermediate participants |
Primary
Number of Participants With Treatment Related Adverse Effects
Number of participants with treatment related adverse effects as assessed using CTCAE v4.0 of pembrolizumab when combined with radiation alone and chemoradiation. Compared as percentage of grade 3 and 4 adverse events with historical control percentages.
Time frame: All adverse events were recorded from the time the consent form is signed through 30 days following cessation of treatment. Any AE related to study drug after 30 days post treatment, subjects were followed until resolution.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants With Treatment Related Adverse Effects | 78 Participants |
Secondary
Overall Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation
• High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins.
Time frame: 1 year
Population: • High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Overall Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation | 93 percentage of high risk participants |
Secondary
Overall Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation
• Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins
Time frame: 1 year
Population: • Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Overall Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation | 100 percentage of intermediate participants |
Secondary
Tumor Immune Response to Pembrolizumab as Defined by PD-L1 CPS in the Baseline Tumor Tissue
Change in distribution of the tumor immune microenvironment after Pembrolizumab administration in tumor biopsy tissue using markers of T cells and T cell activation using PD-L1 CPS. PD-L1 CPS is defined as the PD-L1 combined positive score. PD-L1 CPS is defined as Combined positivity score (CPS) was calculated by summing the numbers of PD-L1-positive tumor cells and immune cells and dividing by the total number of viable tumor cells. Additionally, PD-L1 is a protein that helps the body immune system remain in control. The denominator in this case is 72 subjects that were evaluable. Evaluable means the subject had a pre-surgery pembrolizumab and a biopsy taken. The numerators are explained below.
Time frame: 1 week between receiving a pre-surgery dose of pembrolizumab and surgery when the biopsy was taken
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab | Tumor Immune Response to Pembrolizumab as Defined by PD-L1 CPS in the Baseline Tumor Tissue | PD-L1 CPS in Baseline tumor tissue was zero | 20 Participants |
| Pembrolizumab | Tumor Immune Response to Pembrolizumab as Defined by PD-L1 CPS in the Baseline Tumor Tissue | PD-L1 CPS in Baseline tumor tissue was ≥1 | 52 Participants |