Trial Title:
Safety and Efficacy Study of PRV111 and PRV211 in Subjects with Oral Squamous Cell Carcinoma
NCT ID:
NCT05893888
Condition:
Oral Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Cisplatin
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Phase 1/2, Open-Label, Single-Arm
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PRV211 (Intraoperative Cisplatin System)
Description:
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.
Arm group label:
Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the lip or oral cavity
Other name:
Cisplatin
Intervention type:
Drug
Intervention name:
PRV111 (Cisplatin Transmucosal System)
Description:
PRV111 (Cisplatin Transmucosal System) is a thin, 2-layer, matrix-type, transmucosal
patch consisting of a chitosan matrix layer embedded with cisplatin loaded chitosan
particles (CLPs) and a non-woven fabric adhesive unidirectional backing, which is applied
to the matrix layer during manufacturing. The patch is self-adhesive. In addition to the
PRV111 patch, a separately packaged Permeation Enhancer (PE) Powder for Reconstitution
used in conjunction with PRV111. The reconstituted PE Solution is intended to improve the
absorption of the cisplatin active ingredient and will be applied prior to patch
application.
Arm group label:
Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or oral cavity
Other name:
Cisplatin
Summary:
Arm 1 ( Phase 2/3 Run in ):
PRV111: Topical Locoregional Delivery Placed Over the Tumor Region Primary Endpoint:
Overall Response Rate (ORR) Primary Objective: Demonstrate the safety and efficacy of
PRV111 in patients with Carcinoma in Situ (CIS) (WHO 2017)
Arm 2 (Phase 1) PRV211: Intraoperative Locoregional Delivery Placed into the Resected
Tumor Bed Primary Endpoint: Safety Primary Objective: Determine Safety of PRV211 in
intraoperative setting
Subject Assignment: Subjects will be assigned to Arm 1 or Arm 2 of this study based on
disease staging Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip
or oral cavity Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the
lip or oral cavity
Detailed description:
Privo's PRV111 & PRV211 Product Description:
PRV111 (Cisplatin Transmucosal System) is a thin, 2-layer, matrix-type, transmucosal
patch consisting of a chitosan matrix layer embedded with cisplatin loaded chitosan
particles (CLPs) and a non-woven fabric adhesive unidirectional backing, which is applied
to the matrix layer during manufacturing. The patch is self-adhesive.
In addition to the PRV111 patch, a separately packaged Permeation Enhancer (PE) Powder
for Reconstitution is used in conjunction with PRV111. The reconstituted PE Solution is
intended to improve the absorption of the cisplatin active ingredient and will be applied
prior to patch application.
PRV211 is a nanoengineered 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 micrometastases or close
margins that are unable to be fully resected while avoiding system circulation.
ARM 1 Study Details PRV111 Topical Treatment
Screening: A screening period of up to 7 days is needed to evaluate subject eligibility
for study participation. All subjects will undergo a baseline histopathological
assessment at screening (confirming CIS of the oral cavity for inclusion), if an existing
diagnosis does not exist. Also at screening, the investigator will determine if the
patient requires surgery, and will assess the rest of the inclusion/exclusion criteria to
check for eligibility.
Dose limiting Toxicity (DLT): DLT is defined as a clinically significant
treatment-emergent AE (TEAE) or laboratory abnormality unrelated to surgery and/or
disease progression, concurrent illness, or concomitant therapy within 1-month
post-surgery Note: The dosing of 1.5 mg/cm2 per visit in this protocol is comparable to
the one used in the prior completed phase 1/2 CLN-001 study, which has shown safety and
efficacy causing no dose limiting toxicities (DLTs), related severe adverse events (SAEs)
or systemic side effects.
Photo documentation: Tumors will be photographed including anatomic landmarks at each
visit, prior to treatment at treatment visits for the ability to compare between visits.
Photos are also required for documenting the location of biopsies taken. Additional
details are provided in the Lab Manual.
Minimum Required Treatments for Efficacy Assessment: For assessing efficacy, each subject
must complete at least 3 treatment visits.
Assessment for Postponement of Surgery: Response Assessment Criteria: If disease is not
improved compared to baseline biopsy, subject proceeds to scheduled surgery, otherwise
the subject will continue on with the PRV111 treatment regimen.
ARM 2 Study Details PRV211 Intraoperative Treatment
Screening: A screening period of up to 7 days is needed to evaluate subject eligibility
for study participation. All subjects will be screened based on the SOC biopsy to obtain
baseline histopathology. This biopsy will confirm the stage of the disease to be T1-T3,
Nx, M0 of the oral cavity, amenable to surgery. Based on this confirmation, the rest of
the inclusion/exclusion criteria will be checked for eligibility.
Safety and Efficacy of PRV211 Treatment: The safety of PRV211 treatment will be
determined in the Safety Run-in study described below. Once the safety is determined, a
second expansion study can be initiated in another study. The efficacy of PRV211 is
determined in the expansion study. This efficacy will be assessed by the incidence of
locoregional recurrence at 12 months.
Initial Safety Lead-in Study: This is an open label, safety lead-in phase 1b dose
confirmation study in patients with T1-T3, Nx, M0 oral cancer, followed by an expansion
phase 2 single arm study as an intraoperative chemotherapy with PRV211. For the purpose
of safety detection, if greater than 33% of subjects being evaluated for safety present
with dose-limiting toxicities (DLTs), the study is deemed unsafe.
For the Safety Lead-in Study, 3 subjects will be initially enrolled. If more than 1
subject has dose limiting toxicity (DLT), the study stops. Otherwise, 3 additional
subjects will be enrolled and if more than 2 DLTs are detected in the total of 6
subjects, the study is deemed unsafe and the study stops. If 2 or less DLTs are observed,
the treatment will be considered safe.
At the conclusion of the Safety Lead-in portion (6 patients), if PRV211 is determined to
be safe, an expansion study can be initiated. The 6 subjects from the Safety Lead-in
study will be included in the expansion study and these patients will be monitored for
efficacy.
Criteria for eligibility:
Criteria:
Different diagnosis for ARM 1 & ARM 2, however the rest of inclusion criteria are the
same for both arms:
In order to be eligible to participate in the study, an individual must meet all of the
following criteria:
• Diagnosis Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or
oral cavity Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx,M0 of the lip
or oral cavity
Criteria for Inclusion for both ARM 1 & ARM 2:
1. Tumors for which the cytological and architectural changes upon histopathological
assessment warrant surgical intervention
2. Adult subjects, men and women, defined by age ≥18 years at the time of screening.
3. Tumor must be accessible, with no evidence of infection or active bleeding.
4. Tumor is amenable to surgical resection within 8 weeks of screening visit (Visit 0).
5. Clinically and/or radiologically measurable tumor.
6. Eastern Collaborative Oncology Group Performance Status of ≤2.
7. 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.
8. Absence of any serious underlying medical conditions which could impair the ability
of the subject to participate in the study.
9. Have a life expectancy of ≥3 months.
10. Willing and able to provide written informed consent.
11. Able to return to study site for treatment and follow-up visits as defined in the
Protocol.
Criteria for Exclusion for both ARM 1 and ARM 2 (unless specified):
An individual who meets any of the following criteria will be excluded from participation
in the study:
1. Subjects that are not eligible for surgery as SOC.
2. Patients with a prior history of invasive squamous cell carcinoma (Arm 1 only)
3. Tumors involving the marginal gingiva (Arm 1 only)
4. Squamous cell carcinoma (SCC) of the oral cavity that received previous
radiotherapy.(Arm 1 only)
5. Systemic chemotherapy for the treatment of SCC of the head and neck less than 2
years prior to Screening (Arm 1 only)
6. Concurrent documented malignancy, with the exception of localized SCCs and basal
cell carcinoma of the skin Exposure to any investigational agent within 3 months
prior to Screening
7. 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
8. Active, uncontrolled infection requiring systemic therapy, such as but not limited
to HIV, Syphilis, Hepatitis B, or Hepatitis C
9. 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
10. Known or suspected pregnancy, planned pregnancy, or lactation
11. Any medical or psychiatric condition that may compromise the ability to give written
informed consent
12. Known diagnosis of oral submucous fibrosis (Arm 1 only)
13. Known diagnosis of trismus (Arm 1 only)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The University of Chicago
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alexander Pearson, MD
Phone:
(773) 834-1604
Email:
apearson5@medicine.bsd.uchicago.edu
Start date:
October 16, 2023
Completion date:
October 2026
Lead sponsor:
Agency:
Privo Technologies
Agency class:
Industry
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Privo Technologies
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05893888
