Clinical trial NCT03502148: Safety and Efficacy Study of PRV111 in Subjects With Oral Squamous Cell Carcinoma
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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Oral Squamous Cell Carcinoma
Lead sponsor: Privo Technologies
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2018-04-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase 1/2, Open-Label, Single-Arm
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Determine an Efficacious Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Tumor Responses
timeFrame: Subjects were evaluated for efficacy during the 4 treatment visits in the 21 days prior to surgery
measure: Determine a Safe Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Dose-Limiting Toxicities
timeFrame: 4 treatment visits in the 21 days prior to surgery
Secondary outcomes:
measure: Tumor Response (Tumor Volume Change From Baseline and Pre-op Visit, Approximately 21 Days Prior to Surgical Excision of the Tumor)
timeFrame: Assessed within the 21 days prior to surgical excision of the tumor
measure: Number of Loco-regional Recurrences
timeFrame: Assessed 1, 3 and 6 months post surgery
measure: Tumor and Lymph Node (if Available) Platinum Levels
timeFrame: 21 days from baseline through surgical excision of the tumor
measure: Technical Success - Residual Cisplatin Levels Post-application
timeFrame: 4 treatment visits in the 21 days prior to surgery
measure: Systemic Platinum Levels (Cmax)
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)
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Advanced ENT and Allergy
state: Kentucky
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Houston
country: United States
facility: Ben Taub Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center School of Dentistry
state: Texas
Study officials:
affiliation: CEO, Privo Technologies
name: Manijeh Goldberg, PhD
role: STUDY_DIRECTOR
References:
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.