Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Pembrolizumab (MK-3475) for High Risk Oral Intra-Epithelial Neoplasias

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02882282
Recruitment Status : Recruiting
First Posted : August 29, 2016
Last Update Posted : January 28, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE August 24, 2016
First Posted Date  ICMJE August 29, 2016
Last Update Posted Date January 28, 2019
Actual Study Start Date  ICMJE June 14, 2017
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2016)
Oral Cancer-Free Survival of Patients with High Risk Oral Intra-Epithelial Neoplasias (IEN) Treated with Pembrolizumab Versus Observation [ Time Frame: 7 years ]
Oral cancer-free survival defined as time from randomization to the development of histologically confirmed oral cancer or death of any cause, whichever occurs first.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02882282 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) for High Risk Oral Intra-Epithelial Neoplasias
Official Title  ICMJE Personalized, Randomized, Phase 2 Study of Pembrolizumab (MK-3475) for High Risk Oral Intra-Epithelial Neoplasias
Brief Summary

The goal of this clinical research study is to compare pembrolizumab to standard of care observation (no treatment) in controlling oral pre-malignant lesions and IENs. The safety and tolerability of pembrolizumab will also be studied.

This is an investigational study. Pembrolizumab is FDA approved and commercially available for the treatment of certain types of melanoma and non-small cell lung cancer (NSCLC). It is currently being used for research purposes in head and neck cancer. The study doctor can explain how the study drug is designed to work.

Up to 250 people will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. If you are assigned to Arm A (the control group), you will not receive treatment and will only be observed. If you are in Arm B, you will receive pembrolizumab. This is called randomization.

Both you and the study doctor will know to which group you have been assigned. If you are in Arm A, you will not be able to crossover into Arm B and you will not have any study visits until the end-of-treatment/follow-up visits (described below).

Study Drug Administration:

Each cycle is 3 weeks (21 days).

If you are in Arm B, you will receive pembrolizumab by vein over 30 minutes on Day 1 (+/- 7 days) of Cycles 1-4.

Study Visits (Arm B Only):

On Day 1 of Cycles 2-4:

  • You will have a physical exam.
  • Blood (about 3-4 teaspoons) will be drawn for routine tests.
  • During Cycle 2, blood (about 4 tablespoons) will be drawn for biomarker testing.
  • During Cycle 2, you will have 2 oral swabs for biomarker testing.

Any blood, tissue, and oral swabs left over after study testing (including the follow-up visits described below) will be stored at MD Anderson for use in future biomarker testing, including genetic biomarkers, as described in this consent form.

If at anytime during the study or during follow-up you are diagnosed with oral cancer, or if you previously had oral cancer and it returns:

  • Blood (about 4 tablespoons) will be drawn for biomarker testing.
  • You will have oral swabs for biomarker testing.

Length of Study Participation:

If you are in Arm B, you may receive pembrolizumab for up to 4 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Please speak to your study doctor if you would like to stop receiving the study drug so this can be done safely.

All participants will take part in the end-of-treatment and follow-up visits.

End-of-Treatment Visit:

About 3 months after your first dose of study drug or randomization:

  • You will have a physical exam.
  • Your tobacco and alcohol history will be collected.
  • Blood (about 3-4 teaspoons) will be drawn for routine tests.
  • Blood (about 4 tablespoons) will be drawn for biomarker testing.
  • Oral lesions will be measured and biopsied to check the status of the disease. If you had a lesion and it went away, the area where the lesion was located previously will be biopsied.
  • You will have 2 oral swabs collected for biomarker testing.
  • If you are in Arm B, urine will be collected for routine tests.
  • If you are in Arm B and can become pregnant, blood (about 2 teaspoons) or part of the above urine sample will be collected for a pregnancy test.

Follow-Up Visits:

About 6, 9, 18, 24, and 30 months after your first dose of study drug or randomization:

  • You will have a physical exam.
  • Your tobacco and alcohol history will be collected.
  • At 6 months only and if you are in Arm B, blood (about 3-4 teaspoons) will be drawn for routine tests.

About 12 and 36 months after your first dose of study drug or randomization:

  • You will have a physical exam.
  • Your tobacco and alcohol history will be collected.
  • Blood (about 4 tablespoons) will be drawn for biomarker testing.
  • You will have oral swabs collected for biomarker testing.
  • At 12 months only, blood (about 2 teaspoons) will be drawn for routine tests.
  • At 12 months only, if you have a lesion, it will be measured and biopsied. If you had a lesion and it went away, the area where the lesion was located previously will be biopsied.

Long-Term Follow Up:

You will be contacted (either called, mailed, or e-mailed) to check on how you are doing and your cancer status. This information may also be collected from your medical record, if needed. The study doctor will tell you how often you may be contacted. Each phone call should last about 10 minutes. This contact will continue unless you withdraw from the study.

If you cannot be contacted for any reason, your family members may also be contacted to learn how you are doing. The study staff will ask you for their contact information (such as a phone number or email address). If you do not want to have your family members contacted, you do not have to give the researchers this information.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Oral Pre-malignant Lesion(s)
  • Intra-epithelial Neoplasias
  • History of Invasive Oral Cancer
Intervention  ICMJE Drug: Pembrolizumab
200 mg by vein on Day 1 of a 21 day cycle for 4 cycles.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475
Study Arms  ICMJE
  • Experimental: LOH Pembrolizumab Group

    Loss of Heterozygosity (LOH) positive group.

    Pembrolizumab by vein on Day 1 of Cycles 1-4.

    Intervention: Drug: Pembrolizumab
  • No Intervention: LOH Observational Group

    Loss of Heterozygosity (LOH) positive group.

    Participants only observed during course of study.

Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 24, 2016)
250
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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 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 (2-9).
  2. Be willing and able to provide written informed consent.
  3. Be >/= 18 years of age on day of signing informed consent for the trial.
  4. Be willing to provide tissue from a newly obtained oral biopsy.
  5. Have a performance status of 0-2 on the ECOG Performance Scale.
  6. Demonstrate adequate organ function as defined: Hematological: Absolute Neutrophil Count >/=1,500/mcL, Platelets >/= 75,000/mcL. Hepatic: Serum total bilirubin </= 1.5 X ULN or Direct Bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN. AST (SGOT) and ALT (SGPT) </=2.5 X ULN
  7. 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.
  8. 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.
  9. 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:

  1. 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.
  2. 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.
  3. Has a known history of active TB (Bacillus Tuberculosis).
  4. Hypersensitivity to pembrolizumab or any of its excipients.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Has a known history of, or any evidence of active, non-infectious pneumonitis.
  10. Has an active infection requiring systemic therapy.
  11. 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.
  12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  13. 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.
  14. Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  15. Has a history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  17. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Renata Ferrarotto, MD 713-792-6363 rferrarotto@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02882282
Other Study ID Numbers  ICMJE 2016-0193
NCI-2017-00479 ( Registry Identifier: NCI CTRP )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Renata Ferrarotto, MD M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP