Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Cisplatin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Intensity Modulated Radiation Therapy (IMRT)

Pembrolizumab, 200 mg IV during cycle visits every 3-weeks for up to 6 cycles, or until toxicities are no longer tolerable

Eligible participants will receive Intensity Modulated Radiation Therapy daily x 7 weeks

Intensity Modulated Radiation Therapy

Jared Weiss, MD

This study is being done to evaluate the efficacy of Pembrolizumab, concomitant with and following standard of care definitive radiation, for locally advanced squamous cell carcinoma of the head and neck patients who are not good candidates for Cisplatin.

This open label, phase II trial will enroll 29 subjects in order to evaluate the efficacy of Pembrolizumab, concomitant with and following standard of care definitive radiation for locally advanced squamous cell carcinoma head and neck patients who are not good candidates for Cisplatin. Objectives include estimating progression free survival and overall survival, response rates, safety and toxicity, and quality of life in these patients. Correlative studies, based on serial blood collections and tumor samples, may be done under a separate protocol based on availability of archival diagnostic tissue.

Pembrolizumab + Radiation for Locally Adv SCC of the Head and Neck (SCCHN) Not Eligible Cisplatin

Pembrolizumab and Radiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) Not Eligible for Cisplatin Therapy

the proportion of patients who are alive and free of progression from disease at 20 weeks from the start of treatment

the proportion of patients who are alive and free of progression from disease atoneyears from the start of treatment

the proportion of patients who are alive and free of progression from disease at two years from the start of treatment

Progression Free survival is defined as the time from D1 of treatment to progression or death from any cause.

the proportion of patients who are alive at one year after Day 1 of treatment

the proportion of patients who are alive at two years after Day 1 of treatment

Evaluate the safety of the proposed regimen by Estimating the proportion of patients who receive \<95% of the intended dose of radiation (i.e., \<67 Gray)

Safety was assessed by documenting clinically relevant adverse events, defined as events reported by both the clinician and participant related to concurrent radiation plus pembrolizumab. Clinicians classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). The grading (severity) scale for each AE term: Grade (G) 1 Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; G 2 Moderate; G 3 Severe or medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated; disabling; G 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. Patient assessed toxicity were classified based on the Patient-Reported Outcome version of the CTCAE (PRO-CTCAE) which measures the severity, interference, and frequency of events on a 5 point likert scale (0-4) with a higher score indicating worse or more bothersome event

Overall response rate will be determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) which defines Complete Response (CR) as Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects.

complete response rate will be determined using RECIST 1.1 and is defined as the percentage of participants who achieve a Complete response (CR)-Disappearance of all target lesions. Any pathological lymph node (LN) (whether target or non-target) must have decreased in short axis to \<10mm.

Time to locoregional recurrence is defined from Day 1 of treatment until the first locoregional progression

Time to distant metastasis is defined as the time from day 1 of treatment to progression of disease at a distant site; deaths or other progressions will be censored

The FACT-HN is the FACT-General (FACT-G) and a head and neck cancer specific (HNC) subscale given at baseline, at end of treatment, and at first follow-up visit. The FACT-G is a measure of general QOL with Items rated by patients on a Likert scale from 0 to 4, assessing function in 4 domains: physical well-being (PWB) (7 items, score range 0-28), social-family well-being (SFWB) (7 items, score range 0-28), emotional well-being (EWB) (6 items, score range 0-24) and functional well-being (FWB) (7 items, score range 0-28). The HNC subscale has 12 items and a score range from 0 to 48. Higher scores represent better QOL.

Merck Sharp & Dohme LLC

UNC Lineberger Comprehensive Cancer Center

All patients will receive Intensity Modulated Radiotherapy Treatments (IMRT) as per standard of care. The total dose will be 70 Gray(Gy) at 2Gy/fraction, 35 fractions, Monday to Friday, for 7 weeks.

Starting on the first day of radiotherapy, patients will be treated with pembrolizumab 200 milligrams (mg) intravenous (IV) every 3 weeks for 6 doses.

Pembrolizumab Concomitant With and Post 7 Weeks of Radiation

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Smoking status

For former/current smokers, an estimate of how much they have smoked.

Smoking pack years

East Coast Oncology Group (ECOG) Performance status: 0-5 scale to describe a patient's level of functioning in terms of selfcare ability and activity level (lower score means higher functioning) 0-Fully active

1. Restricted in strenuous activity but ambulatory and able to carry out light work
2. Ambulatory, capable of all selfcare but unable to carry out any work; up and about more than 50% of waking hours
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4. Completely disabled; can't carry on any selfcare; totally confined to bed or chair
5. Dead

Performance status

Reason for cisplatin ineligibility

The Charlson Comorbidity Index is a method of categorizing comorbidities of patients in which each category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient ranging from 0 (no comorbidities) to 24. The higher the score, the more likely the predicted outcome will result in mortality or higher resource use.

Charleson comorbidity index score

Primary site

Anatomic stage is the American Joint Committee on Cancer (AJCC) system, which is based on:

Size of primary tumor (T) and whether it has grown into nearby areas. Spread to regional lymph nodes (N). Spread (metastasis; M) to other organs of the body. Once the T, N, and M categories have been determined, this information is combined into a prognostic stage group. Higher Roman numerals mean the cancer is more advanced.

Stage

The percent of tumor with membrane-specific staining was directly estimated at four intensity levels \[negative (\<1), low (1+), moderate (2+), and high (3+)\] and reported as a percentage quantitatively as any one of the following: 0%, 1%, 2%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 93%, 95%, 99%, or 100%. To calculate MPS, the percents of tumor staining at low, moderate, and high levels were summed. The potential range of the scale is from 0 to 100 with a higher score indicating higher PD-L1.

Programmed cell Death Ligand-1 (PD-L1) Modified Percent Score (MPS)

The percent of tumor with membrane-specific staining was directly estimated at four intensity levels \[negative (\<1), low (1+), moderate (2+), and high (3+)\] and reported as a percentage quantitatively. To calculate MHS, the percent of membrane staining at low levels was multiplied by a factor of 1, the percent of staining at moderate levels was multiplied by 2, and the percent of staining at high levels was multiplied by 3; the three products were then summed to arrive at a final MHS. Potential range of scale is 0 to 300, with a higher score indicating higher expression of PD-L1.

Programmed cell Death Ligand-1 (PD-L1) modified H-score (MHS)

The abundance of TILs present was noted as a number between 0-3 with 0 being the absence of TILs and 3 indicating high profusion of TILs.

Tumor-Infiltrating Lymphocytes (TIL)

Robin V. Johnson

20 Week Progression Free Survival Rate

One Year Progression Free Survival Rate

Two Year Progression Free Survival Rate

Median Progression Free Survival

One Year Overall Survival Rate

Two Year Overall Survival Rate

Proportion of Participants Who Received <95% of Intended Dose of Radiation

Pain

Decreased appetite

Swallowing difficulty

Dry mouth

Fatigue

Number of Participants With Clinically Relevant Adverse Events

Two participants did not complete follow-up radiographic measurements to assess for response

Overall Response Rate

Complete Response Rate

Time to Locoregional Recurrence

Time to Distant Metastasis

SFWB

Baseline Quality of life Measurements

All patients will receive Intensity Modulated Radiotherapy Treatments (IMRT) as per standard of care. The total dose will be 70 Gray(Gy) at 2Gy/fraction, 35 fractions, Monday to Friday, for 7 weeks.

Starting on the first day of radiotherapy, patients will be treated with pembrolizumab 200 milligrams (mg) intravenous (IV) every 3 weeks for 6 doses.

Baseline Assessment - Pembrolizumab Concomitant With and Post 7 Weeks of Radiation

Week 10 Quality of life Measurements

All patients will receive Intensity Modulated Radiotherapy Treatments (IMRT) as per standard of care. The total dose will be 70 Gray(Gy) at 2Gy/fraction, 35 fractions, Monday to Friday, for 7 weeks.

Starting on the first day of radiotherapy, patients will be treated with pembrolizumab 200 milligrams (mg) intravenous (IV) every 3 weeks for 6 doses.

Week 10 Assessment - Pembrolizumab Concomitant With and Post 7 Weeks of Radiation

Week 20 Quality of life Measurements

All patients will receive Intensity Modulated Radiotherapy Treatments (IMRT) as per standard of care. The total dose will be 70 Gray(Gy) at 2Gy/fraction, 35 fractions, Monday to Friday, for 7 weeks.

Starting on the first day of radiotherapy, patients will be treated with pembrolizumab 200 milligrams (mg) intravenous (IV) every 3 weeks for 6 doses.

Week 20 Assessment - Pembrolizumab Concomitant With and Post 7 Weeks of Radiation

Three subjects did not complete the FACT assessments and are therefore not included

Spots Global Cancer Trial Database for Pembrolizumab + Radiation for Locally Adv SCC of the Head and Neck (SCCHN) Not Eligible Cisplatin

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial