Safety and Efficacy Study of PRV211 in Subjects With Oral Squamous Cell Carcinoma

Study Overview
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Brief Summary
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PRV211 is a sterilized nano engineered delivery system intended for intraoperative chemotherapy treatment for all solid tumor surgeries immediately following surgical excision. The goal is to treat the tumor bed locally, eliminating any remaining micro metastases or close margins that are unable to be fully resected while avoiding system circulation. This study will enroll up to 40 subjects. In this study both safety and efficacy will be evaluated. All subjects will be monitored for possible DLTs.

Detailed Description
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Methodology: This is a Phase 1/2, open-label, Safety and Efficacy, Tolerability, Anti-Tumor Effects, Systemic Exposure, and Device Technical Effects of PRV211 (Intraoperative Cisplatin System) in subjects with T2-T3 oral squamous cell carcinoma (SCC) amenable to surgery. Study Design: This study will enroll up to 40 subjects. An interim analysis will take place to evaluate safety and efficacy results and the addition of a second arm (see interim analysis section for further detail). In this study both safety and efficacy will be evaluated. All subjects will be monitored for possible DLTs. For the purpose of dose selection, tolerable dose is defined as a dose where fewer than 33% of subjects being evaluated within the safety population present with dose-limiting toxicities (DLTs). Effective dose is determined based on the evaluable population as described in the Statistical Methods section. The study is described below: Up to 15 subjects will be enrolled for stage 1 and undergo 1 PRV211 treatment application during standard of care tumor resection surgery. Each treatment will include permeation enhancer. If 5 or less respond, the dose can be escalated given safety requirements are met. A total of ten (10) PRV211 patches can be applied in this single application during tumor resection surgery. Definition of Response: A subject will be considered to have responded to the treatment if there is no incidence of locoregional recurrence at 3 months post-surgery and/or adjuvant therapy as indicated on positron emission tomography (PET) scan.

Official Title
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Phase 1/2, Open-Label, Safety and Efficacy, Tolerability, Anti-Tumor Effects, Systemic Exposure, and Device Technical Effects of PRV211 in Subjects With T2-T3 Oral Squamous Cell Carcinoma Amenable to Surgery

Conditions
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Oral Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: PRV211 (Intraoperative Cisplatin System)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects, men and women, defined by age ≥18 years at the time of screening. Pathologically proven and clinically confirmed T2-T3, Nx-N2b, M0 SCC of the lip or oral cavity (anterior 2/3 of the tongue, floor of mouth, lower and upper gingiva, hard palate, and buccal mucosa). Tumor must be amenable to surgical resection. Clinically and/or radiologically measurable tumor. Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤2. Candidates for standard of care treatment consisting of surgery. Male and female subjects of childbearing potential must agree to use 2 methods of effective contraception from screening and for at least 30 days after the final dose of investigational product. Appropriate birth control is defined as barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices, or naturally or surgically sterile (with documentation in the subject's medical records). Postmenopausal women are defined as presenting at least 12 months' natural spontaneous amenorrhea, or at least 6 weeks following surgical menopause (bilateral oophorectomy). Females of childbearing potential must be non-lactating and have a negative serum hCG within 14 days of treatment initiation. Absence of any serious underlying medical conditions which could impair the ability of the subject to participate in the study. Have a life expectancy of ≥6 months. Willing and able to provide written informed consent. Able to return to study site for treatment and follow-up visits as defined in the Protocol. Exclusion Criteria: Concurrent documented malignancy, except for localized SCCs of the skin Exposure to any investigational agent within 3 months prior to Screening Known allergy or hypersensitivity to platinum-containing agents, or known intolerance to a prior platinum-containing agent, or to any of the excipients, which, in the judgement of the physician will preclude re-exposure to platinum-containing agent Active, uncontrolled infection requiring systemic therapy, such as but not limited to HIV, Hepatitis B or C Uncontrolled intercurrent illness that would risk subject safety, interfere with the objectives of the Protocol, or limit subject compliance with study requirements, as determined by the Investigator Known or suspected pregnancy, planned pregnancy, or lactation Any medical or psychiatric condition that may compromise the ability to give written informed consent Test Product, Dose and Mode of Administration: PRV211 (Cisplatin Intraoperative Treatment) consists of:

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 PRV211<br>PRV211 treatment application during standard of care tumor resection surgery. PRV211 system is comprised of two parts, a liquid permeation enhancer (PE) and cisplatin patch. The permeation is brushed onto the resected tumor bed and after 5 minutes the patch can be applied directly over the same area. Apply up to 2 layers of the PRV211 system to the tumor bed post-resection. The duration of the PRV211 treatment takes approximately 10-20 minutes and then the surgeon can continue as planned with the rest of the standard of care procedure. The proposed starting dose is 0.5 mg/cm2 of cisplatin on the tumor bed. This approach can be safe and effective in preventing locoregional recurrence after surgery and eliminating high-risk factors for local recurrence, such as dysplasia at the margins. | Drug: PRV211 (Intraoperative Cisplatin System)<br>* PRV211 system is comprised of two parts, a liquid permeation enhancer (PE) and cisplatin patch. The permeation is brushed onto the resected tumor bed and after 5 minutes the patch can be applied directly over the same area. Apply up to 2 layers of the PRV211 system to the tumor bed post-resection. The duration of the PRV211 treatment takes approximately 10-20 minutes and then the surgeon can continue as planned with the rest of the standard of care procedure. The proposed starting dose is 0.5 mg/cm2 of cisplatin on the tumor bed. This approach can be safe and effective in preventing locoregional recurrence after surgery and eliminating high-risk factors for local recurrence, such as dysplasia at the margins.<br>* Other names: Cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint | Locoregional Recurrence | 3 months post-surgery or completion of adjuvant therapy |