Safety and Efficacy Study of PRV111 in Subjects With Oral Squamous Cell Carcinoma

Study Overview
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Brief Summary
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Up to 31 subjects diagnosed with oral squamous cell carcinoma received one application of a permeation enhancer 3 treatment applications of a Cisplatin drug-loaded patch to the tumor site at each of the 4 treatment visits. These 4 treatment visits were scheduled to occur during the 3 weeks prior to the standard of care tumor resection. Funding Source: FDA OOPD

Detailed Description
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Up to 31 subjects diagnosed with oral squamous cell carcinoma received one application of a permeation enhancer and 3 treatment applications of a Cisplatin drug-loaded patch to the tumor site at each of 4 treatment visits. These 4 treatment visits were scheduled to occur during the 3 weeks prior to the standard of care tumor resection. After the surgery, subjects were followed for 6 months for disease recurrence. Ten subjects were enrolled in the study. Up to 21 additional subjects could have been enrolled in Stage 2, if safety and efficacy endpoints were not met. The dose was not changed. All subjects were followed for 6 months post-surgery for disease recurrence. During and at the conclusion of the treatment period, subjects were monitored for local and systemic safety, tumor response due to the treatment, and systemic drug exposure.

Official Title
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Phase 1/2, Open-Label, Single-Arm Safety and Efficacy Dose-Finding, Systemic Exposure, and Device Technical Effects of PRV111 (Cisplatin Transmucosal System) in Subjects With Oral Squamous Cell Carcinoma

Conditions
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Oral Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: PRV111 (Cisplatin Transmucosal System)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed T1 (<2 cm) or T2 (>2 cm but < or = 4 cm) squamous cell carcinoma (SCC) of the lip or oral cavity (anterior 2/3 of the tongue, floor of mouth, lower and upper gingiva, salivary gland, hard palate, and buccal mucosa). Tumor must be easily accessible, with no evidence of infection or active bleeding, encroaching major vessels or clinical evidence of neural invasion. Not previously irradiated. Tumors must be amenable to surgical resection no later than 21 days post Visit 1. Clinically or radiologically measurable tumor. ECOG Performance Status of < or =2. Adequate renal function as demonstrated by renal creatinine clearance. Adequate organ function as assessed by safety labs. Agree to use effective contraception for 30 days after the last dose of study drug. Absence of any serious medical conditions that would impair the subject's ability to participate. Willing and able to provide written informed consent. Able to return to the study site for treatment and follow-up visits as defined in the protocol. Exclusion Criteria: Known distal metastasis of the SCC of the oral cavity. Systemic chemotherapy for the treatment of SCC of the head and neck less than 2 years prior to screening. Concurrent documented malignancy, with the exception of localized SCC of the skin. Exposure to any investigational agent within 3 months prior to screening. Known allergy or hypersensitivity to platinum-containing agents. Active, uncontrolled infection requiring systemic therapy. Known or suspected pregnancy, planned pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 1/2, Open-Label, Single-Arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-Label, Single Arm Study of PRV111<br>Subjects received 3 treatment applications of PRV111 (Cisplatin Transmucosal System) at each of the 4 planned visits within 3 weeks prior to their tumor surgery. | Drug: PRV111 (Cisplatin Transmucosal System)<br>* Each treatment visit will include one application of a permeation enhancer and then 2, 3 or 5 PRV111 (Cisplatin Transmucosal System) applications depending on the Stage subject is enrolled in.<br>* Other names: cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine an Efficacious Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Tumor Responses | The starting dose was 1.5 mg/cm2 of cisplatin. Based on the incidence of dose-limiting toxicities and tumor response, subjects would either continue to receive the starting dose or the dose would be de-escalated to 1.0 mg/cm2 or escalated to 2.5 mg/cm2. This measures presents the number of tumor responses during the PRV111 treatment period | Subjects were evaluated for efficacy during the 4 treatment visits in the 21 days prior to surgery | 
| Determine a Safe Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Dose-Limiting Toxicities | The starting dose was 1.5 mg/cm2 of cisplatin. Based on the incidence of dose-limiting toxicities and tumor response, subjects would either continue to receive the starting dose or the dose would be de-escalated to 1.0 mg/cm2 or escalated to 2.5 mg/cm2. This measures presents the number of reported dose-limiting toxicities during the PRV111 treatment period | 4 treatment visits in the 21 days prior to surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response (Tumor Volume Change From Baseline and Pre-op Visit, Approximately 21 Days Prior to Surgical Excision of the Tumor) | Assessed by clinical measurement at baseline and at the pre-op visit | Assessed within the 21 days prior to surgical excision of the tumor | 
| Number of Loco-regional Recurrences | Number of loco-regional recurrences at follow-up | Assessed 1, 3 and 6 months post surgery | 
| Tumor and Lymph Node (if Available) Platinum Levels | Levels of platinum content in tumor tissue and/or lymph tissue, using a validated bioanalytical ICP-MS method. Resected tissues were digested via microwave and used to evaluate the amount of cisplatin delivered by PRV111 (Correlated to the amount of platinum detected). | 21 days from baseline through surgical excision of the tumor | 
| Technical Success - Residual Cisplatin Levels Post-application | Platinum content in each residual PRV111, using a validated bioanalytical ICP-MS method and the results for all applications were averaged. | 4 treatment visits in the 21 days prior to surgery | 
| Systemic Platinum Levels (Cmax) | Levels of platinum content in blood, using a validated bioanalytical ICP-MS method. Blood drawn was digested via microwave and used to evaluate the amount of systemic cisplatin exposure from PRV111 (Correlated to the amount of platinum detected). A single value for Cmax was calculated by averaging values for all subjects. | Cmax is a single value of the highest concentration of platinum in the blood reported from samples taken post-dose across all 4 treatment visits (Baseline [0], 30, 60, and 120 minutes at Visits 1-4) |