Pembrolizumab in HNSCC With Residual Disease After Radiation

NCT02892201 | Terminated Phase 2 Results DMC

• 2 other identifiers: 20000280471602017275
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II study for patients with squamous cell carcinoma of the head and neck who have residual disease following definitive therapy with radiation (with or without systemic therapy). Patients must be diagnosed with residual disease within 24 weeks of completion of radiation therapy. Residual disease must be biopsy proven before the patient can consent to the trial, and can be either from lymph nodes in the neck, or from the primary tumor site. Prior to beginning study therapy patients are evaluated by an ENT to determine if they have disease amenable to surgical resection. Both resectable and unresectable patients will be eligible for participation in the study.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  To determine the overall response rate based on RECIST 1.1 to pembrolizumab for patients with residual disease following radiation with or without systemic therapy for squamous cell carcinoma of the head and neck. For lesions considered too small for measurement by RECIST 1.1 a modified response criteria will be used. RECIST categories used for the target lesion are complete response (CR), partial response (PR), stable disease (NR/SD), and progressive disease (PD). Upon entry of results, the time frame was corrected to 12 weeks (see attached protocol).

  12 weeks

Secondary Outcomes (4)

• Change in PD-L1 Expression

  Up to 4 weeks

• Median Progression Free Survival

  Up to 168 weeks

• Overall Survival

  168 weeks

• Median Overall Survival

  Up to 168 weeks

Other Outcomes (3)

• Count of Participants With Immune Related Adverse Events

  12 weeks

• Count of Those With Distant Metastases

  168 Weeks

• Overall Response Rate

  168 weeks

Study Arms (1)

All subjects

EXPERIMENTAL

for patients with squamous cell carcinoma of the head and neck who have residual disease following definitive therapy with radiation Pembrolizumab will be given at a constant dose of 200 mg every three weeks, for four cycles. Patients with resectable disease can then go on to surgery, and patients with unresectable disease can continue on pembrolizumab until progression or for up to 1 year.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

a constant dose of 200 mg every three weeks, for four cycles.

Also known as: Keytruda, MK-3475

All subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be =\> 18 years of age on day of signing informed consent.
• Biopsy proven residual disease.
• Be willing to provide tissue from a newly obtained core biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1 and following completion of RT/CRT.
• Have a performance status of 0 or 1 or 2 on the ECOG Performance Scale.
• Demonstrate adequate organ function. Labs value need to be assessed within 14 days of study treatment.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Patients must have a history of Stage I-IVB SCC of the head and neck arising from the oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx and must have been treated with definitive intent radiation (with or without systemic therapy)
• Patients must be at least 6 weeks (42 days) and no more than 24 weeks (168 days) from completion of radiation with or without systemic therapy at the time of biopsy confirming residual disease. Patients must receive the first dose of study medication no more than 28 weeks following completion of radiation.
• Patients must have pathological evidence of persistent lymph node disease or persistent disease at the primary tumor site with viable tumor cells confirmed by a biopsy within 24 weeks of study treatment and no evidence of metastatic disease following primary radiation with or without systemic therapy confirmed by a CT scan within 4 weeks of study treatment. If a biopsy confirming residual disease has not been performed, this can be performed after obtaining consent during the screening procedures.
• Persistent lymph node disease with viable tumor cells will be determined by the histological determination of tumor viability.
• All persistent disease must have received at least 66 Gy in 1.8-2Gy fractions of radiotherapy to the area of residual disease (or a biologically equivalent dose given by the linear quadratic equation: biologically equivalent dose (BED) = nd (1 + d/( α/β), where n is the number of fractions, d dose per fraction and the α/β ratio for tumor is 10. Previous radiation records will be obtained to confirm adequate dosing.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving supraphysiologic doses of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. A physiologic dose of steroids is defined as up to 10mg of prednisone daily (or its equivalent).
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from acute, non-hematological adverse events due to agents administered more than 4 weeks earlier, unless otherwise approved by the Principal Investigator.
• Note: Subjects with ≤ Grade 2 neuropathy, any grade dysphagia, ≤ Grade 2 pain, ≤ Grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any grade xerostomia, and any grade dysgeusia, are an exception to this criterion and may qualify for the study. Also please note that the presence of a feeding tube to aid with nutrition does not disqualify patients from study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first protocol treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from acute, non-hematological adverse events due to a previously administered agent, unless otherwise approved by the Principal Investigator.
• Note: Subjects with ≤ Grade 2 neuropathy, any grade dysphagia, ≤ Grade 2 pain, ≤ Grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any grade xerostomia, and any grade dysgeusia, are an exception to this criterion and may qualify for the study. Also please note that the presence of a feeding tube to aid with nutrition does not disqualify patients from study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has 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.
• Has known history of non-infectious pneumonitis that required steroids, or current pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Yale University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

University of Texas Southwestern Medical Center (UTSW)

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Barbara Burtness, MD
• Organization: Yale School of Medicine

arbara.burtness@yale.edu

(203) 200-4622

Study Officials

• Barbara Burtness, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: September 8, 2016
• Study Start: September 8, 2016
• Primary Completion: February 1, 2020
• Study Completion: March 1, 2020
• Last Updated: July 29, 2025
• Results First Posted: November 18, 2023

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)