Trial Outcomes & Findings for Safety and Efficacy Study of PRV111 in Subjects With Oral Squamous Cell Carcinoma (NCT NCT03502148)

Last Updated: 2022-10-21

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Subjects were evaluated for efficacy during the 4 treatment visits in the 21 days prior to surgery

Results posted on

2022-10-21

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-Label, Single Arm Study of PRV111 n=10 Participants 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). Each treatment included one application of permeation enhancer prior to PRV111 administration.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	10 participants n=99 Participants
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=99 Participants
Age, Categorical >=65 years	5 Participants n=99 Participants
Age, Continuous	64.3 years STANDARD_DEVIATION 12.15 • n=99 Participants
Sex: Female, Male Female	5 Participants n=99 Participants
Sex: Female, Male Male	5 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	8 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: Subjects were evaluated for efficacy during the 4 treatment visits in the 21 days prior to surgery

Population: The efficacy population consists of all subjects who completed at least 3 PRV111 treatment visits and met all inclusion/exclusion criteria. The outcome measure is expressed as the count of participants who displayed a tumor response (At least 30% tumor volume reduction based on clinical measurements).

Outcome measures

Outcome measures
Measure	Neoadjuvant PRV111 (Efficacy Population) n=8 Participants Subjects who completed at least 3/4 planned PRV111 treatment visits.
Determine an Efficacious Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Tumor Responses	7 Participants

PRIMARY outcome

Timeframe: 4 treatment visits in the 21 days prior to surgery

Population: Patients treated with at least 1 PRV111 were included

Outcome measures

Outcome measures
Measure	Neoadjuvant PRV111 (Efficacy Population) n=10 Participants Subjects who completed at least 3/4 planned PRV111 treatment visits.
Determine a Safe Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Dose-Limiting Toxicities	0 dose-limiting toxicities

SECONDARY outcome

Timeframe: Assessed within the 21 days prior to surgical excision of the tumor

Population: Subjects who received at least 3 PRV111 treatments and met all inclusion/exclusion criteria.

Assessed by clinical measurement at baseline and at the pre-op visit

Outcome measures

Outcome measures
Measure	Neoadjuvant PRV111 (Efficacy Population) n=8 Participants Subjects who completed at least 3/4 planned PRV111 treatment visits.
Tumor Response (Tumor Volume Change From Baseline and Pre-op Visit, Approximately 21 Days Prior to Surgical Excision of the Tumor)	69 percentage of tumor volume reduction Interval 35.0 to 100.0

SECONDARY outcome

Timeframe: Assessed 1, 3 and 6 months post surgery

Population: Subjects received at least 3 treatment applications of PRV111 (Cisplatin Transmucosal System) at each of the 4 planned visits within 3 weeks prior to their tumor surgery.

Number of loco-regional recurrences at follow-up

Outcome measures

Outcome measures
Measure	Neoadjuvant PRV111 (Efficacy Population) n=8 Participants Subjects who completed at least 3/4 planned PRV111 treatment visits.
Number of Loco-regional Recurrences	0 number of locoregional recurrences

SECONDARY outcome

Timeframe: 21 days from baseline through surgical excision of the tumor

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).

Outcome measures

Outcome measures
Measure	Neoadjuvant PRV111 (Efficacy Population) n=10 Participants Subjects who completed at least 3/4 planned PRV111 treatment visits.
Tumor and Lymph Node (if Available) Platinum Levels Average Tumor Platinum Level	337 µg/g Interval 33.0 to 1395.0
Tumor and Lymph Node (if Available) Platinum Levels Average Lymph Node Platinum Level	110 µg/g Interval 11.0 to 305.0

SECONDARY outcome

Timeframe: 4 treatment visits in the 21 days prior to surgery

Population: Each patch was analyzed

Platinum content in each residual PRV111, using a validated bioanalytical ICP-MS method and the results for all applications were averaged.

Outcome measures

Outcome measures
Measure	Neoadjuvant PRV111 (Efficacy Population) n=10 Participants Subjects who completed at least 3/4 planned PRV111 treatment visits.
Technical Success - Residual Cisplatin Levels Post-application	91.7 percentage of drug released Standard Deviation 3.2

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	Neoadjuvant PRV111 (Efficacy Population) n=10 Participants Subjects who completed at least 3/4 planned PRV111 treatment visits.
Systemic Platinum Levels (Cmax)	0.24 µM Interval 0.09 to 0.62

Adverse Events

Neoadjuvant PRV111 (Safety Population)

Serious events: 3 serious events

Other events: 10 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Neoadjuvant PRV111 (Safety Population) n=10 participants at risk Subjects received at least 3 treatment applications of PRV111 (Cisplatin Transmucosal System) at each of the 4 planned visits within 3 weeks prior to their tumor surgery.
Metabolism and nutrition disorders Failure to Thrive	10.0% 1/10 • Number of events 1 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Infections and infestations Post-Surgical Infected Seroma	10.0% 1/10 • Number of events 1 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications Surgical Complication	10.0% 1/10 • Number of events 1 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).

Other adverse events

Other adverse events
Measure	Neoadjuvant PRV111 (Safety Population) n=10 participants at risk Subjects received at least 3 treatment applications of PRV111 (Cisplatin Transmucosal System) at each of the 4 planned visits within 3 weeks prior to their tumor surgery.
Gastrointestinal disorders [During PRV111 Treatment Period] Oral Pain	40.0% 4/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Glossodynia	30.0% 3/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Lip Blister	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Stomatitis	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Constipation	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
General disorders Fatigue	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Oral Mucosal Blistering	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Tongue Blistering	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Tongue Discomfort	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Nausea	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Cardiac disorders [During PRV111 Treatment Period] Angina Pectoris	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] oropharyngeal pain	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] salivary duct inflammation	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Dysphagia	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Swollen Tongue	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Gastro Esophageal Reflux Disease	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Dry Mouth	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Tongue Ulceration	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [During PRV111 Treatment Period] Toothache	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
General disorders [During PRV111 Treatment Period] Non-cardiac Chest pain	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
General disorders [During PRV111 Treatment Period] Oedema Peripheral	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications [During PRV111 Treatment Period] Palate Injury	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Metabolism and nutrition disorders [During PRV111 Treatment Period] Decreased Appetite	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Nervous system disorders [During PRV111 Treatment Period] Headache	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Respiratory, thoracic and mediastinal disorders [During PRV111 Treatment Period] Cough	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications [Post-PRV111 Treatment, Post-Surgery] Procedural Pain	60.0% 6/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications [Post-PRV111 Treatment, Post-Surgery] Procedural Complication	30.0% 3/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Respiratory, thoracic and mediastinal disorders [Post-PRV111 Treatment, Post-Surgery] Acute Respiratory Failure	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Psychiatric disorders [Post-PRV111 Treatment, Post-Surgery] Anxiety	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [Post-PRV111 Treatment, Post-Surgery] Constipation	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [Post-PRV111 Treatment, Post-Surgery] Dysphagia	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [Post-PRV111 Treatment, Post-Surgery] Malnutrition	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications [Post-PRV111 Treatment, Post-Surgery] Post-Procedural Complication	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [Post-PRV111 Treatment, Post-Surgery] Nausea	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications [Post-PRV111 Treatment, Post-Surgery] Post Procedural Oedema	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications [Post-PRV111 Treatment, Post-Surgery] Procedural Nausea	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
General disorders [Post-PRV111 Treatment, Post-Surgery] Pyrexia	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Infections and infestations [Post-PRV111 Treatment, Post-Surgery] Infected seroma	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Gastrointestinal disorders [Post-PRV111 Treatment, Post-Surgery] Gastroesophageal Reflux Disease	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
General disorders [Post-PRV111 Treatment, Post-Surgery] Fatigue	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications [Post-PRV111 Treatment, Post-Surgery] post operative hypertension	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Injury, poisoning and procedural complications [Post-PRV111 Treatment, Post-Surgery] skin graft failure	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Investigations [Post-PRV111 Treatment, Post-Surgery] weight decreased	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Metabolism and nutrition disorders [Post-PRV111 Treatment, Post-Surgery] fluid overload	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Metabolism and nutrition disorders [Post-PRV111 Treatment, Post-Surgery] hyperglycemia	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Metabolism and nutrition disorders [Post-PRV111 Treatment, Post-Surgery] hypervolemia	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Metabolism and nutrition disorders [Post-PRV111 Treatment, Post-Surgery] hypophosphatemia	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Metabolism and nutrition disorders [Post-PRV111 Treatment, Post-Surgery] lactic acidosis	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Metabolism and nutrition disorders [Post-PRV111 Treatment, Post-Surgery] malnutrition	20.0% 2/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Nervous system disorders [Post-PRV111 Treatment, Post-Surgery] dysarthria	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Psychiatric disorders [Post-PRV111 Treatment, Post-Surgery] agitation	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Psychiatric disorders [Post-PRV111 Treatment, Post-Surgery] insomnia	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Renal and urinary disorders [Post-PRV111 Treatment, Post-Surgery] urinary retention	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Respiratory, thoracic and mediastinal disorders [Post-PRV111 Treatment, Post-Surgery] acute pulmonary oedema	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Respiratory, thoracic and mediastinal disorders [Post-PRV111 Treatment, Post-Surgery] dysphonia	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Respiratory, thoracic and mediastinal disorders [Post-PRV111 Treatment, Post-Surgery] pleural effusion	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Respiratory, thoracic and mediastinal disorders [Post-PRV111 Treatment, Post-Surgery] productive cough	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Skin and subcutaneous tissue disorders [Post-PRV111 Treatment, Post-Surgery] skin disorder	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Skin and subcutaneous tissue disorders [Post-PRV111 Treatment, Post-Surgery] swelling face	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Vascular disorders [Post-PRV111 Treatment, Post-Surgery] hypotension	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).
Vascular disorders [Post-PRV111 Treatment, Post-Surgery] shock	10.0% 1/10 • Adverse event data was collected during the PRV111 treatment period up to the last follow up visit (up to 6 months post surgery).

Additional Information

Dr. Manijeh Goldberg

Privo Technologies

Phone: 9785872322

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place