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

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 250
• Participant gender: Both

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Pembrolizumab
• Last Updated: 2016-11-21

Criteria

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 Eastern Cooperative Oncology Group (ECOG) Performance Scale.

6. Demonstrate adequate organ function as defined: Hematological: Absolute Neutrophil Count >/=1,500/mcL, Platelets >/= 75,000/mcL. Hepatic: Serum total bilirubinX upper limit of normal ( ULN) or Direct Bilirubinbilirubin levels > 1.5 ULN. AST (SGOT) and ALT (SGPT)

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.,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.,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.