Neoplasms

Symptoms and General Pathology

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Leukoplakia

Leukoplakia, Oral

Precancerous Conditions

Pathological Conditions, Anatomical

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Proliferative Verrucous Leukoplakia

Oral Cancer

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* 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

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

Glenn Hanna, MD

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

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.

Safety and Efficacy of Nivolumab in Treating Oral Proliferative Verrucous Leukoplakia

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.

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.

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.

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 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.

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.

2-year OS rate was defined as the percentage of participants alive at 2 years.

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.

Bristol-Myers Squibb

Dana-Farber Cancer Institute

Principal Investigator

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Per the source vocabulary (CTCAEv4.0) there is a category "Other, specify" for each system organ class. No further data is available to specify classification beyond this general term.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Measure Description: Eastern Cooperative Oncology Group (ECOG) PS: (PS0) Fully active, able to carry on all pre-disease performance without restriction (PS1) Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature

ECOG Performance Status (PS)

Best Overall Response Rate (BORR)

This analysis population represents the subset of participants who have completed questionnaires at both baseline and end of treatment.

COMD QLQ Score Change From Baseline to End of Treatment

Grade 1/2 Toxicity Rate

Grade 3/4 Toxicity Rate

This analysis dataset is comprised of the participants who had next surgery.

Time to the Next Surgery for a Head and Neck Malignancy

Cancer Free Survival at 2 Years (CFS2)

2-year Overall Survival (OS) Rate

PD-L1 Combined Positive Scores (CPS)

Overall Study

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Communicable Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Opportunistic Infections

AIDS-Related Opportunistic Infections

AIDS-Related Complex

Leukoplakia, Hairy

Virus Diseases

Epstein-Barr Virus Infections

Herpesviridae Infections

DNA Virus Infections

Anti-Infective Agents

Acyclovir

Antiviral Agents

To evaluate the efficacy of oral acyclovir for the treatment and suppression of Epstein-Barr virus (EBV) related hairy leukoplakia (HL). To determine the long-term safety of acyclovir in the AIDS-related complex (ARC) patient with HL. To monitor the progression of HIV disease in the HL patient and compare to existing historical control data.

Treatment and Suppression of Hairy Leukoplakia in ARC Patients With Oral Acyclovir (ACV)

Glaxo Wellcome

Carcinoma

Lip and Oral Cavity Cancer

Oral Leukoplakia

Central Nervous System Depressants

Anesthetics

Each patient will receive the surgical excision of the lesion and subsequent follow-up

Each patient will receive clinical follow-up of the lesion with periodical incisional tissue biopsy.

The surgical removal of the lesion, performed within 3 months from the final diagnosis, will follow these steps:

* local anesthesia
* excision of the lesion with surgical blade or laser, according to the clinical case, paying attention to having at least 2 mm-free margins
* silk or resorbable suture for wound closure

The patient will be recall after 14 days for assessing the wound healing and after 30 days for providing and explaining him the histopahtological exam.

The patient will receive a 3-6 month follow-up according to the clinical and histopathological case.

Surgical excision of the lesion

The patient will receive a 3-6 month follow-up according to the clinical and histopathological case, with periodical incisional biopsy every 4 control visit.

In case of OSCC onset during the first 3 months after the final diagnosis, the patient will be excluded since the oral cancer occurence will be considered as a misdiagnosis, more than a "true" malignat progression.

Wait and see approach

Giovanni Lodi, PhD, DMD

Paolo Arduino, DDS

Giovanni Lodi

This research protocol is comparing the effectiveness of surgical excision to the "wait and see" approach for the management of oral leukoplakia and erythroleukoplakia in prevention of oral squamous cell carcinoma onset.

Different treatments have been proposed for the management of oral leukoplakia (OL) in order to prevent oral squamous cell carcinoma onset. However, there is still no consensus on the most effective approach for the patients affected by such oral potentially malignant disorders. Surgery is often performed, but there is no randomized clinical trial which demonstrates its real effectiveness in preventing oral cancer onset.

A recent RCT compared surgical treatment with "wait and see approach" care in patients with nondysplastic OL, assuming that regular clinical follow-up could be considered a reliable standard of care among patients with nondysplastic oral leukoplakias.

The purpose of this study is to evaluate effectiveness of surgical excision in treating OL and or reducing the onset of potential oral squamous cell carcinoma, with a follow-up of 5 years. This study will be the first RCT comparing the effectiveness of surgery to "wait and see approach" in the management of both dysplastic and nondysplastic oral leukoplakias.

Oral Potentially Malignant Disorders: Comparison Between Surgical Treatment and Wait and See Approach

Comparison Between Surgical Excision and "Wait and See" Approach in the Treatment of Oral Leukoplakia: a Randomized, Controlled Clinical Trial

Number of patients who will develop oral squamous cell carcinoma

Period of time required to develop malignancy

To evaluate the quality of life of patients affected by leukoplakia and treated with surgical excision, via Functional Intraoral Glasgow Scale (FIGS) questionnaire. FIGS is a simple point scale used to assess a patient's ability to speak, chew and swallow. Each of these functions is scored independently on a scale of 1-5, five being no disability and one meaning the patient has an inability to speak, chew, or swallow.

University of Milan

Associate Professor

Ear, Nose, and Throat Diseases

Musculoskeletal Diseases

Ulcer

Oral Ulcer

Oropharyngeal Neoplasms

Tongue Neoplasms

Lip Neoplasms

Gingival Neoplasms

Palatal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Tongue Diseases

Gingival Diseases

Periodontal Diseases

Jaw Neoplasms

Skull Neoplasms

Bone Neoplasms

Bone Diseases

Jaw Diseases

Patients at an intermediate and high level of clinical risk for HNSCC and scheduled for initial and immediate incisional diagnostic biopsy of their Oral Cavity.

Patients at an intermediate to high level of clinical risk for HNSCC and scheduled for initial and immediate incisional diagnostic biopsy of their Oropharnyx

Patients at a lower level of clinical risk for HNSCC and not scheduled for an immediate biopsy. Patients will be offered medical management and have an initial RAPID test. All patients will return within 1-3 months for follow-up test and a possible biopsy if clinically indicated.

A noninvasive point of care salivary rinse test performed as 1) a one-time test for patients presenting with suspicion of OPMD and scheduled for biopsy and 2) a multi-administered test for patients presenting with suspicious lesions not scheduled for biopsy.

OncAlert

Objectives Validate the OncAlert® RAPID Test by demonstrating that NPV \> (1 -prevalence).

Evaluate the independent and associated contribution of readily available clinical variables including age, race, gender, HPV status, socioeconomic level, tobacco, and alcohol use with the biopsy and test results.

Evaluate OncAlert® RAPID Test results in patients without immediate biopsy, both at baseline and scheduled follow-up visit (approximately 1-3 months±14 days), to assess impact on outcome.

Planned Number of Subjects A total enrollment of up to 1000 individuals is projected with 600 as the minimum accrued. Patients in the primary cohort (1a and 1b) will be followed until pathology of clinically directed incisional / diagnostic biopsy pathology report is received.

Up to 200 'non-biopsy subjects' will be followed during a 1-3 month ±14 days clinic visit.

Patient Population

Cohorts 1a and 1b:

Subjects with a clinical suspicion of oral potentially malignant disorders, oral or oropharyngeal cancer, or both based in part on clinical examination, symptoms, clinical history, suspicious lesion(s) in mouth without history of a prior positive biopsy. Even if the suspicion is low for cancer or precancer, the patient is eligible if a biopsy is performed, in part, to rule this out. For example, if a subject has findings on imaging, or worrisome localizing symptoms in the oral cavity or oropharynx, they would be eligible. In addition, subjects with papillomas or other findings where there is a low level of concern, but cancer is still in the differential, are also eligible.

* Cohort 1a: oral cavity
* Cohort 1b: oropharynx

Cohort 2:

Subjects are enrolled with a clinical suspicion of oral potentially malignant disorders, oral or oropharyngeal cancer, or both based in part on clinical examination, symptoms, clinical history, suspicious lesion(s) in mouth without history of a prior positive biopsy; however, based on clinical impression and or patient related issues no immediate biopsy is obtained.

Screen Fail Rate: A 20% Screen Fail Rate is anticipated.

Investigational Product Name: OncAlert Oral Cancer RAPID Test (OncAlert RAPID)

Methodology Overview

Prospectively collect 5cc of normal saline after a combination of swish, gargle and spit into the provided collection specimen cup. Specimens will be collected at baseline (time of biopsy) as per standard practice at each site. The OncAlert RAPID Test cassette is inserted into the specimen cup and read directly from the cassette in 10 minutes. In addition, comprehensive clinical - pathology and patient demographic features including age, gender, race, ethnicity, and all pathology biopsy results will be collected. Any pertinent additional clinical data including HPV status, socioeconomic status, smoking, drinking history, and pertinent features related to oral health will be obtained. A central pathology review for all biopsy results will be performed and incorporated into the final analyses.

Overview

The OncAlert Oral Cancer RAPID Test (OncAlert RAPID) is a qualitative point-of-care lateral flow assay to aid in the decision to biopsy in patients with clinical features associated with oral potentially malignant disorders and or oral/oropharyngeal cancer (i.e. head and neck squamous cell carcinoma).

Proposed Intended Use Statement

The device measures soluble CD44 and total protein in saliva samples collected in saline. The test is an adjunct to the biopsy decision process, and not intended as a screening or stand-alone diagnostic assay. To be used in adults 23 years and older. Not intended for use in pregnant women.

STUDY OBJECTIVES

The principal objectives of this study are to:

* Validate the OncAlert RAPID Test, with an NPV ≥ (1-prevalence),
* Evaluate OncAlert RAPID Test results in patients without immediate biopsy, both at baseline and scheduled follow-up visit (approximately 1-3 months), to assess impact on outcome,
* Evaluate the independent and associated contribution of readily available clinical variables including age, race, gender, HPV status, socioeconomic level, tobacco, and alcohol use with the biopsy and test results.

STUDY OVERVIEW

Study Approach

Prospectively collect 5cc of normal saline after a combination of swish, gargle and spit into the provided collection specimen cup. 1cc will be removed and sequestered for subsequent downstream analyses (Section 7). Specimens will be collected at baseline (time of biopsy) as per standard practice at each site. The OncAlert RAPID Test cassette is inserted into the specimen cup and read directly from the cassette in 10 minutes. In addition, acquire comprehensive clinical - pathology and patient demographic features including age, gender, race, ethnicity, and all pathology biopsy results. Also, obtain any pertinent additional clinical data including HPV status, socioeconomic status, smoking, drinking history, and pertinent features related to oral health. It is presumed that some patients within the current biopsy protocol will undergo treatment as a result of the biopsy diagnosis. The clinical-pathology data, when accessible, for these patients will be collected for subsequent secondary analyses. A central pathology review for all biopsy results will be performed and incorporated into the final analyses.

Study Duration

For Cohorts 1a and 1b patients, the pathology results of clinically directed incisional / diagnostic biopsy will be followed until finalized and received.

Cohort 2 patients not having an initial incisional / diagnostic biopsy at the initial visit will have an additional OncAlert® RAPID test performed within 1 -3 months±14 days (or as defined by standard of care (SOC)after the initial visit.)

The study will conclude after all data is collected and analyzed. This could vary from 12 to 36 months or more depending on accrual rates at the open sites and other factors.

Clinical Evaluation of the OncAlert RAPID in Subjects Presenting for Evaluation and/or Initial Biopsy; Impact on Decision-Making

Clinical Evaluation of the OncAlert RAPID; Impact on Decision-Making

The likelihood of a positive biopsy was determined when either the presence of a CD44 band or Total Protein above a specific gradient were positive.

Evaluate OncAlert RAPID results in patients without immediate biopsy, both at baseline and repeat results at scheduled follow-up visit (approximately 1-3 months). If biopsy performed associate RAPID positive vs. negative results with biopsy outcome. If not biopsy is performed, compare results with clinical decision for not to biopsy.

Pearl Pathways

Vigilant Biosciences, Inc.

Erythroplasia

Erythroplakia

Gastrointestinal Agents

Dermatologic Agents

Erythromycin

Erythromycin Estolate

Erythromycin Ethylsuccinate

Erythromycin stearate

Isotretinoin

SBS-101

Placebo

Joy Schleyer

This study will be the first study investigating the safety, pharmacokinetics (PK), and efficacy of SBS-101 on oral pre-malignant lesions. As such, no clinical data has yet been generated using SBS-101 oral adhesive film.

This Study is to Evaluate the Safety and Pharmacokinetics of SBS-101 in Patients With Oral Premalignant Lesions

A Phase 1, Randomized, Double-blind, Placebo Controlled, Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of SBS-101 After Intraoral Application in Patients With Oral Premalignant Lesions (OPL)

Overall response is defined as complete or partial response in either clinical or histological outcome without worsening of either.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy of Nivolumab in Treating Oral Proliferative Verrucous Leukoplakia	NCT03692325	Leukoplakia, Or...	Nivolumab	18 Years -	Dana-Farber Cancer Institute
Treatment and Suppression of Hairy Leukoplakia in ARC Patients With Oral Acyclovir (ACV)	NCT00002026	Leukoplakia, Ha... HIV Infections	Acyclovir	18 Years -	NIH AIDS Clinical Trials Information Service
Oral Potentially Malignant Disorders: Comparison Between Surgical Treatment and Wait and See Approach	NCT04858100	Leukoplakia, Or...	Surgical excisi... Wait and see ap...	18 Years -	University of Milan
Clinical Evaluation of the OncAlert RAPID in Subjects Presenting for Evaluation and/or Initial Biopsy; Impact on Decision-Making	NCT03239834	Palatal Neoplas... Lip Neoplasm Gingival Neopla... Leukoplakia, Or... Tongue Neoplasm... Oropharyngeal N... Oral Ulcer	OncAlert	23 Years -	Vigilant Biosciences, Inc.
Safety and Efficacy of Nivolumab in Treating Oral Proliferative Verrucous Leukoplakia	NCT03692325	Leukoplakia, Or...	Nivolumab	18 Years -	Dana-Farber Cancer Institute
This Study is to Evaluate the Safety and Pharmacokinetics of SBS-101 in Patients With Oral Premalignant Lesions	NCT03939364	Leukoplakia, Or...	SBS-101 Placebo	18 Years -	Skyline Biosciences

Spots Global Cancer Trial Database for leukoplakia, oral