Back to resultsSafety and Efficacy Study of PRV111 in Subjects With Oral Squamous Cell Carcinoma (PRV111)
Primary Purpose
Oral Squamous Cell Carcinoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PRV111 (Cisplatin Transmucosal System)
Sponsored by
About this trial
This is an interventional treatment trial for Oral Squamous Cell Carcinoma
Eligibility Criteria
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.
Sites / Locations
- Advanced ENT and Allergy
- University of Cincinnati Cancer Institute
- Ben Taub Hospital
- Memorial Hermann Hospital
- The University of Texas Health Science Center School of Dentistry
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open-Label, Single Arm Study of PRV111
Arm Description
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.
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
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
Number of Loco-regional Recurrences
Number of loco-regional recurrences at follow-up
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).
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.
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.
Full Information
NCT ID
NCT03502148
First Posted
March 4, 2018
Last Updated
September 26, 2022
Sponsor
Privo Technologies
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03502148
Brief Title
Safety and Efficacy Study of PRV111 in Subjects With Oral Squamous Cell Carcinoma
Acronym
PRV111
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
June 19, 2018 (Actual)
Primary Completion Date
October 27, 2019 (Actual)
Study Completion Date
May 6, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Privo Technologies
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Squamous Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Phase 1/2, Open-Label, Single-Arm
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open-Label, Single Arm Study of PRV111
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PRV111 (Cisplatin Transmucosal System)
Other Intervention Name(s)
cisplatin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determine an Efficacious Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Tumor Responses
Description
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
Time Frame
Subjects were evaluated for efficacy during the 4 treatment visits in the 21 days prior to surgery
Title
Determine a Safe Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Dose-Limiting Toxicities
Description
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
Time Frame
4 treatment visits in the 21 days prior to surgery
Secondary Outcome Measure Information:
Title
Tumor Response (Tumor Volume Change From Baseline and Pre-op Visit, Approximately 21 Days Prior to Surgical Excision of the Tumor)
Description
Assessed by clinical measurement at baseline and at the pre-op visit
Time Frame
Assessed within the 21 days prior to surgical excision of the tumor
Title
Number of Loco-regional Recurrences
Description
Number of loco-regional recurrences at follow-up
Time Frame
Assessed 1, 3 and 6 months post surgery
Title
Tumor and Lymph Node (if Available) Platinum Levels
Description
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).
Time Frame
21 days from baseline through surgical excision of the tumor
Title
Technical Success - Residual Cisplatin Levels Post-application
Description
Platinum content in each residual PRV111, using a validated bioanalytical ICP-MS method and the results for all applications were averaged.
Time Frame
4 treatment visits in the 21 days prior to surgery
Title
Systemic Platinum Levels (Cmax)
Description
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.
Time Frame
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manijeh Goldberg, PhD
Organizational Affiliation
CEO, Privo Technologies
Official's Role
Study Director
Facility Information:
Facility Name
Advanced ENT and Allergy
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
University of Cincinnati Cancer Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Ben Taub Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Memorial Hermann Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The University of Texas Health Science Center School of Dentistry
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35977936
Citation
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.
Results Reference
derived
Learn more about this trial
Safety and Efficacy Study of PRV111 in Subjects With Oral Squamous Cell Carcinoma
We'll reach out to this number within 24 hrs