Safety and Efficacy of Nivolumab in Treating Oral Proliferative Verrucous Leukoplakia

NCT ID: NCT03692325

Last Updated: 2024-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-05
• Study Completion Date: 2024-08-30

Brief Summary

This research study is studying an immunotherapy drug, as a possible treatment for oral proliferative verrucous leukoplakia (OPVL).

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug or combination of drugs to learn whether it works in treating a specific disease. "Investigational" means that the drug/s is being studied.

The purpose of this study is to evaluate effectiveness (how well the drug works) of nivolumab in treating OPVL and or prolonging the onset of possible malignancy.

Nivolumab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells. Nivolumab has been demonstrated to activate the immune system to attack cancer cells in participants with different types of cancers. OPVL has a high risk for turning into cancer and the investigators are testing if nivolumab may help to shrink the white lesions in the participant's mouth and reduce cancer risk.

In November 2016, the Food and Drug Administration (FDA) approved nivolumab for the treatment of participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Squamous cell carcinoma is the kind of cancer that OPVL can transform into.

Conditions

Leukoplakia, Oral

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Nivolumab

• Nivolumab will be administered by IV infusion on Day 1 of each 28-day cycle
• Treatment with the study drug will continue for a maximum of 4 cycles or until unacceptable toxicity or withdrawal of consent

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Nivolumab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells.

Interventions

Nivolumab

Nivolumab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells.

Intervention Type: DRUG

Other Intervention Names

Opdivo

Eligibility Criteria

Inclusion Criteria

• Subject must have histologically confirmed oral proliferative verrucous leukoplakia (OPVL), as defined by: multifocal lesions (≥ 2) or contiguous lesions ≥ 3 cm or a single lesion ≥ 4 cm in largest diameter (at least one lesion with any degree of dysplasia). (Note: no restriction on the length of time that patients have had one or more existing lesions)
• Willing to provide blood and tissue from diagnostic biopsies

Exclusion Criteria

• Age 18 years or older
• ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A)
• Participant must have normal organ and marrow function as defined below within 21 days prior to study registration:

• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,000/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤2.0 g/dL
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
• Ability to understand and the willingness to sign a written informed consent document
• Women of childbearing potential (WOCBP) must agree to use appropriate method(s) of contraception. WOCBP should plan to use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 iu/l or equivalent units of hcg) at screening. Pregnancy test will be repeated on the day of the first dose of study drug (before administration), although results of this test are not required for registration.
• "Women of childbearing potential (WOCBP)" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
• Men who are sexually active with WOCBP must agree to use any contraceptive method with a failure rate of less than 1% per year. Men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception

• Known carcinoma in situ (CIS) or invasive squamous cell carcinoma of the oral cavity. A history of a prior stage III (T1-2N1, T3N0) or IV (T1-3N2, T4N0) invasive head & neck squamous cell carcinoma treated with surgery and radiation with or without chemotherapy. Patients with prior locoregionally advanced tumors treated with surgery alone are eligible.
• Existing significant autoimmune conditions. Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded. Patients cannot be on long-term (> 4 weeks) corticosteroids at doses exceeding prednisone 20 mg (or its equivalent) prior to enrollment. Short-term corticosteroid dosing is permitted as long as steroids are discontinued within 2 weeks of study registration.
• Subject who has had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Subject who has been treated with immunotherapy. This includes prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency.
• Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA is negative).
• A personal history of hematopoietic stem cell or solid organ transplant.
• Known non-infectious pneumonitis or any history of interstitial lung disease.
• A personal history of other active malignancies, with the exception of non-melanomatous skin cancers, low-risk prostate adenocarcinoma on active surveillance, or treated cancers in remission for the last 5 years

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Glenn J. Hanna

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Glenn Hanna, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

Hanna GJ, Villa A, Nandi SP, Shi R, ONeill A, Liu M, Quinn CT, Treister NS, Sroussi HY, Vacharotayangul P, Goguen LA, Annino DJ Jr, Rettig EM, Jo VY, Wong KS, Lizotte P, Paweletz CP, Uppaluri R, Haddad RI, Cohen EEW, Alexandrov LB, William WN Jr, Lippman SM, Woo SB. Nivolumab for Patients With High-Risk Oral Leukoplakia: A Nonrandomized Controlled Trial. JAMA Oncol. 2024 Jan 1;10(1):32-41. doi: 10.1001/jamaoncol.2023.4853.

Reference Type: DERIVED

PMID: 37971722 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

18-387

Identifier Type: -

Identifier Source: org_study_id