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Pembrolizumab in Treating Patients With High Risk Oral Intraepithelial Neoplasia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02882282
Recruitment Status : Active, not recruiting
First Posted : August 29, 2016
Last Update Posted : April 18, 2023
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This randomized phase II trial studies how well pembrolizumab works in treating patients with high risk oral intraepithelial neoplasia. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Condition or disease Intervention/treatment Phase
Oral Cavity Carcinoma Oral Intraepithelial Neoplasia Other: Laboratory Biomarker Analysis Other: Patient Observation Biological: Pembrolizumab Phase 2

Detailed Description:


I. To determine oral cancer-free survival of patients with high risk oral intra-epithelial neoplasias (IEN) treated with pembrolizumab versus observation.


I. To determine the safety and tolerability of pembrolizumab for patients with oral IEN.

II. To determine the histologic and clinical response rates (in the subgroup of patients with clinically evident measurable oral IEN lesions) to pembrolizumab.

III. To characterize the immune infiltrate in oral IEN lesions before and after treatment with pembrolizumab.


I. To assess predictive, tissue-and blood-based, biomarkers of benefit from pembrolizumab in oral IEN.

II. To determine the presence of neo-antigens in IEN lesions before and after treatment, and their correlation with oral cancer-free survival and immune infiltrate characteristics.

III. To evaluate the oral micro-biome before and after treatment with pembrolizumab and its association with neo-antigens and benefit from treatment.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo observation.

ARM B: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6, 9, 12, 18, 24, 30, and 36 months and then periodically thereafter.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Personalized, Randomized, Phase 2 Study of Pembrolizumab (MK-3475) for High Risk Oral Intra-Epithelial Neoplasias
Actual Study Start Date : June 14, 2017
Estimated Primary Completion Date : March 1, 2024
Estimated Study Completion Date : March 1, 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Arm A (observation)
Patients undergo observation.
Other: Patient Observation
Undergo observation
Other Names:
  • Active Surveillance
  • deferred therapy
  • expectant management
  • Observation
  • watchful waiting

Experimental: Arm B (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Primary Outcome Measures :
  1. Oral cancer-free survival [ Time Frame: From randomization to the development of histologically confirmed oral cancer or death of any cause, whichever occurs first, assessed up to 7 years ]
    Will be estimated by Kaplan-Meier method.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histological evidence of oral intra-epithelial neoplasia within 12 months prior to enrollment; subjects with a history or clinical diagnosis suggestive of oral intra-epithelial neoplasia, or patients with a history of invasive oral cancer are eligible, but must have a confirmed histological diagnosis of oral intra-epithelial neoplasia before randomization; histological evidence of oral intraepithelial neoplasia on an invasive oral cancer resection specimen is acceptable; a visible, measurable, clinical lesion (such as leukoplakia and/or erythroplakia) is not required; only individuals with high risk profiles will be considered eligible for randomization; high risk profiles are defined as patients without a prior oral cancer and have loss of heterozygosity (LOH) at 3p14 and/or 9p21 plus at least at one additional chromosomal site (4q,8p,11p,13q, or 17p) or patients with a prior oral cancer history and have LOH at 3p14 and/or 9p21; all high risk patients must also meet the additional eligibility criteria
  • Be willing and able to provide written informed consent
  • Be greater than or equal to 18 years of age on day of signing informed consent for the trial
  • Be willing to provide tissue from a newly obtained oral biopsy
  • Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 75,000/mcL
  • Serum total bilirubin =< 1.5 X upper limit of normal (ULN) or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN
  • Female subject of childbearing potential should have a negative urine or serum pregnancy test < 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 study therapy through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses > 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 the study therapy

Exclusion Criteria:

  • Is currently participating and receiving study therapy with potential anti-neoplastic activity, or has participated in a study of an investigational agent and received study therapy with potential anti-neoplastic activity within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • 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 2 at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 2 or at baseline) from adverse events due to a previously administered agent; Note: If the 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 other than adjuvant hormonal therapy; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin or in situ cervical cancer
  • 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has a known history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant, or breastfeeding, or expecting to conceive or father children within the projected duration of treatment with pembrolizumab, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02882282

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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Renata Ferrarotto M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02882282    
Other Study ID Numbers: 2016-0193
NCI-2017-00479 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0193 ( Other Identifier: M D Anderson Cancer Center )
First Posted: August 29, 2016    Key Record Dates
Last Update Posted: April 18, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma in Situ
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action