Safety and Efficacy of Nivolumab in Treating Oral Proliferative Verrucous Leukoplakia

NCT03692325 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-387
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Leukoplakia, Oral

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (BORR)

  BORR on treatment is the percentage of participants who achieved CR or PR. Best overall response is the best response recorded from study registration until the first disease progression/diagnosis of invasive OSCC (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Best overall response was determined by using composite scores based on both measurement and histology, matching to the response grid as following, (1)CR, a decrease of \>80% or more; (2)PR, a decrease of 40-80%; (3)SD, neither PR or PD, (4)PD, an increase of 10% or more.

  Participants were followed up to 164 days.

Secondary Outcomes (7)

• COMD QLQ Score Change From Baseline to End of Treatment

  Assessed at baseline and end of treatment. Treatment duration in days was a median (range) of 105 (21-164).

• Grade 1/2 Toxicity Rate

  Participants were followed up to 194 days.

• Grade 3/4 Toxicity Rate

  Participants were followed up to 194 days.

• Time to the Next Surgery for a Head and Neck Malignancy

  Participants were followed up to 13.3 months.

• Cancer Free Survival at 2 Years (CFS2)

  Participants were followed up to 2 years.

Study Arms (1)

Nivolumab

EXPERIMENTAL

* 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

Drug: Nivolumab

Interventions

Nivolumab DRUG

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

Also known as: Opdivo

Nivolumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 37971722 DERIVED

MeSH Terms

Conditions

Leukoplakia, Oral

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Leukoplakia; Precancerous Conditions; Mouth Diseases; Stomatognathic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Glenn Hanna, MD
• Organization: Dana-Farber Cancer Institute

gjhanna@partners.org

617-632-3090

Study Officials

• Glenn Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: October 2, 2018
• Study Start: December 5, 2018
• Primary Completion: September 1, 2022
• Study Completion: August 30, 2024
• Last Updated: October 1, 2024
• Results First Posted: April 22, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)