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

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

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

Study Overview

• Status: Completed
• Conditions: Oral Squamous Cell Carcinoma
• Intervention / Treatment: Drug: PRV111 (Cisplatin Transmucosal System)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Advanced ENT and Allergy
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital
    • Houston, Texas, United States, 77030
      • Ben Taub Hospital
    • Houston, Texas, United States, 77054
      • The University of Texas Health Science Center School of Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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).
2. 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.
3. Tumors must be amenable to surgical resection no later than 21 days post Visit 1.
4. Clinically or radiologically measurable tumor.
5. ECOG Performance Status of < or =2.
6. Adequate renal function as demonstrated by renal creatinine clearance.
7. Adequate organ function as assessed by safety labs.
8. Agree to use effective contraception for 30 days after the last dose of study drug.
9. Absence of any serious medical conditions that would impair the subject's ability to participate.
10. Willing and able to provide written informed consent.
11. Able to return to the study site for treatment and follow-up visits as defined in the protocol.

Exclusion Criteria:

1. Known distal metastasis of the SCC of the oral cavity.
2. Systemic chemotherapy for the treatment of SCC of the head and neck less than 2 years prior to screening.
3. Concurrent documented malignancy, with the exception of localized SCC of the skin.
4. Exposure to any investigational agent within 3 months prior to screening.
5. Known allergy or hypersensitivity to platinum-containing agents.
6. Active, uncontrolled infection requiring systemic therapy.
7. Known or suspected pregnancy, planned pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-Label, Single Arm Study of PRV111; 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); 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.; Other Names: cisplatin

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Privo Technologies
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Director: Manijeh Goldberg, PhD, CEO, Privo Technologies

Publications and helpful links

General Publications

• Goldberg M, Manzi A, Birdi A, Laporte B, Conway P, Cantin S, Mishra V, Singh A, Pearson AT, Goldberg ER, Goldberger S, Flaum B, Hasina R, London NR, Gallia GL, Bettegowda C, Young S, Sandulache V, Melville J, Shum J, O'Neill SE, Aydin E, Zhavoronkov A, Vidal A, Soto A, Alonso MJ, Rosenberg AJ, Lingen MW, D'Cruz A, Agrawal N, Izumchenko E. A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer. Nat Commun. 2022 Aug 17;13(1):4829. doi: 10.1038/s41467-022-31859-3. Erratum In: Nat Commun. 2022 Dec 21;13(1):7865.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2018
• Primary Completion (Actual): October 27, 2019
• Study Completion (Actual): May 6, 2020

Study Registration Dates

• First Submitted: March 4, 2018
• First Submitted That Met QC Criteria: April 10, 2018
• First Posted (Actual): April 18, 2018

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: CLN-001; FD-R-006325 (Other Grant/Funding Number: FDA OOPD); 5R44CA192875-05 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No