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 larynx cancer. The standard of care treatment will include chemotherapy and radiation for 7 weeks.
Detailed description
This study is an open label, single arm study which will enroll patients with locally advanced squamous cell carcinomas of the larynx. Positive tumor PDL1 expression by IHC will not be required for enrollment. All patients with receive Pembrolizumab and cisplatin in combination with radiation. Pembrolizumab 200 mg flat dose given Q21 days will begin 3 weeks prior to initiation of chemoradiation and continued through the 21-day cycle until completion of chemoradiation. Cisplatin will be given 100 mg/m2 every 21 days during radiation as per standard of care. Pembrolizumab has well defined toxicities as single agent and has non-overlapping mechanisms of action with cisplatin and radiation. The safety of these agents used in combination has not been previously described, therefore the study will begin with a safety run-in phase 1 followed by the phase II design. See statistical section for details.
Interventions
DRUGPembrolizumab
200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses
RADIATIONRadiation Therapy
70 Gy in 35 fractions over 7 weeks
DRUGCisplatin
100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.
Sponsors
Merck Sharp & Dohme LLC
Vinita Takiar
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
* Biopsy-proven, previously untreated stage III or IV squamous cell carcinoma of the larynx, Primary tumor stage (T2, T3) and nodal stage (N0, N1, N2, N3). * Measurable disease based on RECIST 1.1. * Performance status 0 or 1 on Eastern Cooperative Oncology Group Performance Scale. * Anticipated survival minimum of 12 months. * Adequate labs
Exclusion criteria
* Patients with T1 primary tumor or T4 large volume tumor that has resulted in larynx dysfunction at baseline (for example tumor largely penetrating into base of tongue and resulting in inability to swallow at baseline) * Prior radiation therapy to the larynx area or involved neck. * Distant metastasis * 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 Grade 3 or 4 Adverse Events as Assessed by CTCAE V4.0 | 30 days following completion of treatment for the first 6 participants | Greater than 2 grade 3 or 4 adverse events that are definitely, probably or possibly related to the pembrolizumab in the first cohort of 6 participants |
| Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma | 18 months | This is the number of subjects that are laryngectomy-free at 18 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma | 12 months | This is the number of subjects that are laryngectomy-free at 12 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Pembrolizumab every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin
Pembrolizumab: 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses
Radiation Therapy: 70 Gy in 35 fractions over 7 weeks
Cisplatin: 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Pembrolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 54 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 3 / 9 |
Outcome results
Primary
Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma
This is the number of subjects that are laryngectomy-free at 18 months.
Time frame: 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma | 9 Participants |
Primary
Number of Participants With Treatment-Related Grade 3 or 4 Adverse Events as Assessed by CTCAE V4.0
Greater than 2 grade 3 or 4 adverse events that are definitely, probably or possibly related to the pembrolizumab in the first cohort of 6 participants
Time frame: 30 days following completion of treatment for the first 6 participants
Population: These are the first six participants that completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Number of Participants With Treatment-Related Grade 3 or 4 Adverse Events as Assessed by CTCAE V4.0 | 2 Participants |
Secondary
Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma
This is the number of subjects that are laryngectomy-free at 12 months.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma | 9 Participants |