Leukoplakia, Oral
Conditions
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.
Interventions
DRUGNivolumab
Nivolumab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells.
Sponsors
Bristol-Myers Squibb
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Any smoking history is permitted. A history of prior or current tobacco use is not an
Exclusion criteria
. While discouraged, patients are permitted to continue tobacco use while on the study. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate (BORR) | Participants were followed up to 164 days. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grade 1/2 Toxicity Rate | Participants were followed up to 194 days. | The proportion of participants who experienced a maximum grade 1 or 2 adverse events regardless of treatment attribution based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms. |
| Grade 3/4 Toxicity Rate | Participants were followed up to 194 days. | The proportion of participants who experienced a maximum grade 3 or 4 adverse events regardless of treatment attribution based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms. |
| Time to the Next Surgery for a Head and Neck Malignancy | Participants were followed up to 13.3 months. | Time to Next Surgery is defined as time from the first study treatment to any head & neck surgery or resection for biopsy-proven carcinoma in situ (CIS) or invasive oral carcinoma. |
| 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). | Quality of Life was evaluated using COMD QLQ (chronic oral mucosal diseases quality of life questionnaire). The range of the possible total score is 0-104, and low score is a good QoL. |
| 2-year Overall Survival (OS) Rate | Participants were followed up to 2 years. | 2-year OS rate was defined as the percentage of participants alive at 2 years. |
| PD-L1 Combined Positive Scores (CPS) | PD-L1 CPS assessed at baseline. | PD-L1 CPS (programmed death-1 ligand 1 combined positive score) was calculated by dividing the number of PD-L1 staining cells by the total number of viable tumor cells and then multiplying by 100. Its range of possible values was 0-100, where higher scores were better when participants received PD-L1 targeted therapy. |
| Cancer Free Survival at 2 Years (CFS2) | Participants were followed up to 2 years. | CFS2 is the probability of participants remaining alive and cancer-free at 2 years based on Kaplan-Meier methodology. Cancer-Free Survival (CFS) is defined as the time from study registration to development of invasive oral cancer or death due to any cause. Participants alive without disease progression or recurrence (of invasive oral cancer) are censored at date of last disease evaluation. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from Dec 2018 to Jan 2022.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Progression/Recurrence | 2 |
Baseline characteristics
| Characteristic | Nivolumab |
|---|---|
| Age, Continuous | 64.7 Years |
| ECOG Performance Status (PS) PS 0 | 30 Participants |
| ECOG Performance Status (PS) PS 1 | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants |
| Race/Ethnicity, Customized White | 31 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 33 |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 6 / 33 |
Outcome results
Primary
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.
Time frame: Participants were followed up to 164 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab | Best Overall Response Rate (BORR) | 36.4 percentage of participants |
Secondary
2-year Overall Survival (OS) Rate
2-year OS rate was defined as the percentage of participants alive at 2 years.
Time frame: Participants were followed up to 2 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab | 2-year Overall Survival (OS) Rate | 100 Percentage of participants |
Secondary
Cancer Free Survival at 2 Years (CFS2)
CFS2 is the probability of participants remaining alive and cancer-free at 2 years based on Kaplan-Meier methodology. Cancer-Free Survival (CFS) is defined as the time from study registration to development of invasive oral cancer or death due to any cause. Participants alive without disease progression or recurrence (of invasive oral cancer) are censored at date of last disease evaluation.
Time frame: Participants were followed up to 2 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab | Cancer Free Survival at 2 Years (CFS2) | 0.728 Probability |
Secondary
COMD QLQ Score Change From Baseline to End of Treatment
Quality of Life was evaluated using COMD QLQ (chronic oral mucosal diseases quality of life questionnaire). The range of the possible total score is 0-104, and low score is a good QoL.
Time frame: Assessed at baseline and end of treatment. Treatment duration in days was a median (range) of 105 (21-164).
Population: This analysis population represents the subset of participants who have completed questionnaires at both baseline and end of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab | COMD QLQ Score Change From Baseline to End of Treatment | -3 Units on a scale |
p-value: 0.38Wilcoxon (Mann-Whitney)
Secondary
Grade 1/2 Toxicity Rate
The proportion of participants who experienced a maximum grade 1 or 2 adverse events regardless of treatment attribution based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.
Time frame: Participants were followed up to 194 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab | Grade 1/2 Toxicity Rate | 0.75 proportion of participants |
Secondary
Grade 3/4 Toxicity Rate
The proportion of participants who experienced a maximum grade 3 or 4 adverse events regardless of treatment attribution based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.
Time frame: Participants were followed up to 194 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab | Grade 3/4 Toxicity Rate | 0.21 proportion of participants |
Secondary
PD-L1 Combined Positive Scores (CPS)
PD-L1 CPS (programmed death-1 ligand 1 combined positive score) was calculated by dividing the number of PD-L1 staining cells by the total number of viable tumor cells and then multiplying by 100. Its range of possible values was 0-100, where higher scores were better when participants received PD-L1 targeted therapy.
Time frame: PD-L1 CPS assessed at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab | PD-L1 Combined Positive Scores (CPS) | 10 score on a scale |
Secondary
Time to the Next Surgery for a Head and Neck Malignancy
Time to Next Surgery is defined as time from the first study treatment to any head & neck surgery or resection for biopsy-proven carcinoma in situ (CIS) or invasive oral carcinoma.
Time frame: Participants were followed up to 13.3 months.
Population: This analysis dataset is comprised of the participants who had next surgery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab | Time to the Next Surgery for a Head and Neck Malignancy | 6.5 Months |