Oral Squamous Cell Carcinoma
Conditions
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.
Interventions
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.
Sponsors
National Cancer Institute (NCI)
Privo Technologies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1/2, Open-Label, Single-Arm
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine an Efficacious Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Tumor Responses | Subjects were evaluated for efficacy during the 4 treatment visits in the 21 days prior to surgery | 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 | 4 treatment visits in the 21 days prior to surgery | 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
| Measure | Time frame | Description |
|---|---|---|
| Tumor and Lymph Node (if Available) Platinum Levels | 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). |
| Tumor Response (Tumor Volume Change From Baseline and Pre-op Visit, Approximately 21 Days Prior to Surgical Excision of the Tumor) | Assessed within the 21 days prior to surgical excision of the tumor | Assessed by clinical measurement at baseline and at the pre-op visit |
| Systemic Platinum Levels (Cmax) | 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. |
| Technical Success - Residual Cisplatin Levels Post-application | 4 treatment visits in the 21 days prior to surgery | Platinum content in each residual PRV111, using a validated bioanalytical ICP-MS method and the results for all applications were averaged. |
| Number of Loco-regional Recurrences | Assessed 1, 3 and 6 months post surgery | Number of loco-regional recurrences at follow-up |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). Each treatment included one application of permeation enhancer prior to PRV111 administration. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Open-Label, Single Arm Study of PRV111 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 64.3 years STANDARD_DEVIATION 12.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
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
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant PRV111 (Efficacy Population) | Determine an Efficacious Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Tumor Responses | 7 Participants |
Primary
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
Time frame: 4 treatment visits in the 21 days prior to surgery
Population: Patients treated with at least 1 PRV111 were included
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant PRV111 (Efficacy Population) | Determine a Safe Dose (mg/cm2) of PRV111 (Cisplatin Transmucosal System) Via Number of Dose-Limiting Toxicities | 0 dose-limiting toxicities |
Secondary
Number of Loco-regional Recurrences
Number of loco-regional recurrences at follow-up
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant PRV111 (Efficacy Population) | Number of Loco-regional Recurrences | 0 number of locoregional recurrences |
Secondary
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.
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)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Neoadjuvant PRV111 (Efficacy Population) | Systemic Platinum Levels (Cmax) | 0.24 µM |
Secondary
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.
Time frame: 4 treatment visits in the 21 days prior to surgery
Population: Each patch was analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neoadjuvant PRV111 (Efficacy Population) | Technical Success - Residual Cisplatin Levels Post-application | 91.7 percentage of drug released | Standard Deviation 3.2 |
Secondary
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).
Time frame: 21 days from baseline through surgical excision of the tumor
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Neoadjuvant PRV111 (Efficacy Population) | Tumor and Lymph Node (if Available) Platinum Levels | Average Tumor Platinum Level | 337 µg/g |
| Neoadjuvant PRV111 (Efficacy Population) | Tumor and Lymph Node (if Available) Platinum Levels | Average Lymph Node Platinum Level | 110 µg/g |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Neoadjuvant PRV111 (Efficacy Population) | 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 |