Trial of NanoPac® Focal Therapy in Subjects With Prostate Cancer

• Sponsor: NanOlogy, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03077659
• Collaborator: US Biotest, Inc. (Industry)
• Enrollment: 16
• Location: 1
• Arms: 3
• Actual Duration (Months): 12.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Open-label, dose rising, Phase IIa trial of intratumorally-injected NanoPac® 6, 10, or 15 mg/mL in subjects with prostate cancer scheduled for prostatectomy.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate	Drug: NanoPac®	Phase 2

Detailed Description

In this open-label, dose rising, Phase IIa trial with an expanded cohort at the dose of NanoPac® determined to have the best tolerability and safety profile, subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy. The study will include a dose escalation phase and a dose confirmation phase.

In the dose escalation phase, NanoPac® concentrations of 6, 10, and 15 mg/mL in an injection volume of 20% of the lobe of the prostate containing the dominant lesion will be studied in cohorts of 3, with cohorts enrolled sequentially starting at the lowest concentration. Following DSMB review of the cohort data the next cohort may begin enrolling, or an additional 3 at the current dose may be enrolled, or if the first dose does not provide adequate safety and tolerability the study may be halted. The dose determined to be the most suitable for further evaluation, defined as the highest dose with an acceptable safety and tolerability profile as determined by the DSMB, will enroll additional subjects to provide a cohort of 12 subjects at that dose level.

Tumor volume and serum prostate-specific antigen (PSA) will be determined prior to NanoPac® injection. Pharmacokinetic samples, PSA, and ejaculate will be collected in the interval between injection and prostatectomy. Imaging with mpMRI will be performed prior to NanoPac® injection and prior to prostatectomy. Prostate and pelvic lymph nodes excised at prostatectomy will be evaluated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Open-label, dose rising, Phase IIa trial. The study will include a dose escalation phase and a dose confirmation phase. In the dose escalation phase, NanoPac® concentrations of 6, 10, and 15 mg/mL in an injection volume of 20% of the lobe of the prostate containing the dominant lesion will be studied in cohorts of 3, with cohorts enrolled sequentially starting at the lowest concentration. Following DSMB review of the cohort data the next cohort may begin enrolling, or an additional 3 at the current dose may be enrolled, or if the first dose does not provide adequate safety and tolerability the study may be halted. The dose determined to be the most suitable for further evaluation, defined as the highest dose with an acceptable safety and tolerability profile as determined by the DSMB, will enroll additional subjects (dose confirmation phase) to provide a cohort of 12 subjects at that dose level.Open-label, dose rising, Phase IIa trial. The study will include a dose escalation phase and a dose confirmation phase. In the dose escalation phase, NanoPac® concentrations of 6, 10, and 15 mg/mL in an injection volume of 20% of the lobe of the prostate containing the dominant lesion will be studied in cohorts of 3, with cohorts enrolled sequentially starting at the lowest concentration. Following DSMB review of the cohort data the next cohort may begin enrolling, or an additional 3 at the current dose may be enrolled, or if the first dose does not provide adequate safety and tolerability the study may be halted. The dose determined to be the most suitable for further evaluation, defined as the highest dose with an acceptable safety and tolerability profile as determined by the DSMB, will enroll additional subjects (dose confirmation phase) to provide a cohort of 12 subjects at that dose level.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IIa Dose Escalation Trial of NanoPac® Focal Therapy for Prostate Cancer in Subjects Undergoing Radical Prostatectomy
• Actual Study Start Date: Sep 6, 2017
• Actual Primary Completion Date: Oct 4, 2018
• Actual Study Completion Date: Oct 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NanoPac® 6 mg/mL NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume	Drug: NanoPac®; Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.; Other Names: Paclitaxel
Experimental: NanoPac® 10 mg/mL NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume	Drug: NanoPac®; Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.; Other Names: Paclitaxel
Experimental: NanoPac® 15 mg/mL NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume	Drug: NanoPac®; Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.; Other Names: Paclitaxel

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) [Day 1 to Day 29]

   Treatment Emergent Adverse Events included laboratory assessments, physical examination findings, and vital signs.

Secondary Outcome Measures

1. Tumor Response Based on Change in Image Volume on mpMRI [Up to three months prior to consent and Day 29]

   Tumor response to treatment with NanoPac was determined by evaluating the change in image volume with multiparametric MRI (mpMRI) within three months prior to consent and again within 48 hours of the prostatectomy procedure (Day 29). In those cases where two dimensions/axes were available, width was imputed to height for the purposes of calculation, i.e. the lesion was assumed to be an oblate spheroid. In those cases where only one dimension/axis was available, that dimension/axis was imputed for all three dimensions i.e. the lesion was assumed to be a sphere. For this reason, analyses were performed for all subjects with two dimensions available, as well as those for which at least one dimension was available. The data presented for this outcome measure is the one dimension lesion volume calculation: Lesion Volume (cc) = (3.14/6)*(length)³, where length is the longer or only measured dimension.

2. Tumor Response Based on Histologic Evaluation of Biopsied Prostate Samples (Gleason Score) [Screening and Day 29]

   Prostate tissue samples were obtained via biopsy at baseline and immediately prior to prostatectomy (Day 29). Histologic evaluation of these samples was used to determine the Gleason score, and the results at baseline and Day 29 were used to evaluate the tumor response to treatment with NanoPac®. The Gleason score is calculated by adding together the two grades of cancer cells that make up the largest areas of the biopsied tissue sample. The Gleason score usually ranges from 6 to 10. The lower the Gleason score, the more the cancer cells look like normal cells and are likely to grow and spread slowly; a higher Gleason score is likely to indicate a worse outcome. The Gleason score is used to help plan treatment and determine prognosis.

3. Percentage of Sample Considered Adenocarcinoma [Day 29 (prostatectomy)]

   Tissues excised from the primary tumor during prostatectomy (Day 29) were evaluated for the percentage considered adenocarcinoma

4. Concentration of Paclitaxel in the Systemic Circulation [Day 1, Day 8, Day 15, Day 22, and Day 29]

   Pharmacokinetic samples were taken on Day 1 at 1, 2, 4, and 6 hours post-injection, and weekly until prostatectomy. All numeric paclitaxel concentration data above the Lower Limit of Quantitation (25 pg/mL) was tabulated by cohort.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male; 18 years of age and older

• Histopathologically proven adenocarcinoma, Gleason grade ≥ 7 of the prostate planned radical prostatectomy; appropriate for treatment with paclitaxel therapy

• ECOG of 0 or 1

• Laboratory requirements:

• WBC >2500/mm3

• Neutrophil >1500/mm3

• Hemoglobin >10 mg/dL

• Platelet >100,000/ mm3

• AST and ALT <2.5 x ULN

• Total bilirubin <1.5 x ULN

• Creatinine <2 mg/dL

• Normal PT/INR and PTT;

• Willing to use appropriate contraception from time of NanoPac® injection until prostatectomy

• Willing to receive an mpMRI

Exclusion Criteria:

• Evidence of locally advanced or metastatic disease;

• Prostate size ≥ 50 cc

• Prior prostatectomy

• Anticipated use of concomitant chemotherapy (other than the protocol specified agents), immunotherapy, or systemic use of hormonal therapy (such as GnRH analogs, antiandrogens, androgen receptor inhibitors, and 5-α reductase inhibitors) prior to surgery

• Treatment with a prior investigational agent within 30 days of first dose of investigational medication

• Any previous local treatment of the prostate (i.e. radiation)

• Any other condition (e.g. psychiatric disorder) that, in the opinion of the Investigator, may interfere with the patient's ability to comply with the study requirements or visit schedule

• Known sensitivity to any of the study medication components

• History of prior malignancy that has not been in remission for >5 years, with the exception of basal cell or squamous cell carcinoma.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033

Sponsors and Collaborators

• NanOlogy, LLC
• US Biotest, Inc.

Investigators

• Study Director: Shelagh Verco, PhD, US Biotest, Inc.

Study Documents (Full-Text)

• Study Protocol - Aug 8, 2017
• Statistical Analysis Plan - Nov 13, 2018

More Information

Publications

None provided.

• Responsible Party: NanOlogy, LLC
• ClinicalTrials.gov Identifier: NCT03077659
• Other Study ID Numbers: NANOPAC-2016-02
• First Posted: Mar 13, 2017
• Last Update Posted: Aug 20, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by NanOlogy, LLC: prostate cancer; prostatic neoplasms; genital neoplasms, male; urogenital neoplasms; prostatic diseases
• Additional relevant MeSH terms: Prostatic Neoplasms; Paclitaxel

Study Results

Participant Flow

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.
Period Title: Overall Study
STARTED	3	3	10
COMPLETED	3	3	9
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL	Total
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.	Total of all reporting groups
Overall Participants	3	3	10	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.0 (12.3)	73.3 (7.8)	63.8 (7.9)	65.4 (9.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	3 100%	3 100%	10 100%	16 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	2 66.7%	2 20%	5 31.3%
Not Hispanic or Latino	2 66.7%	1 33.3%	7 70%	10 62.5%
Unknown or Not Reported	0 0%	0 0%	1 10%	1 6.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 10%	1 6.3%
White	3 100%	2 66.7%	8 80%	13 81.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 33.3%	1 10%	2 12.5%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	10 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability)
Description	Treatment Emergent Adverse Events included laboratory assessments, physical examination findings, and vital signs.
Time Frame	Day 1 to Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.
Measure Participants	3	3	10
All TEAEs	3 100%	2 66.7%	6 60%
Possibly Related TEAEs	3 100%	0 0%	1 10%

2. Secondary Outcome

Title	Tumor Response Based on Change in Image Volume on mpMRI
Description	Tumor response to treatment with NanoPac was determined by evaluating the change in image volume with multiparametric MRI (mpMRI) within three months prior to consent and again within 48 hours of the prostatectomy procedure (Day 29). In those cases where two dimensions/axes were available, width was imputed to height for the purposes of calculation, i.e. the lesion was assumed to be an oblate spheroid. In those cases where only one dimension/axis was available, that dimension/axis was imputed for all three dimensions i.e. the lesion was assumed to be a sphere. For this reason, analyses were performed for all subjects with two dimensions available, as well as those for which at least one dimension was available. The data presented for this outcome measure is the one dimension lesion volume calculation: Lesion Volume (cc) = (3.14/6)*(length)³, where length is the longer or only measured dimension.
Time Frame	Up to three months prior to consent and Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.
Measure Participants	3	3	9
Lesion Volume at Screening	3.19 (1.46)	0.89 (0.44)	4.89 (5.12)
Lesion Volume at Day 29	1.80 (0.98)	1.91 (1.50)	5.10 (7.79)

3. Secondary Outcome

Title	Tumor Response Based on Histologic Evaluation of Biopsied Prostate Samples (Gleason Score)
Description	Prostate tissue samples were obtained via biopsy at baseline and immediately prior to prostatectomy (Day 29). Histologic evaluation of these samples was used to determine the Gleason score, and the results at baseline and Day 29 were used to evaluate the tumor response to treatment with NanoPac®. The Gleason score is calculated by adding together the two grades of cancer cells that make up the largest areas of the biopsied tissue sample. The Gleason score usually ranges from 6 to 10. The lower the Gleason score, the more the cancer cells look like normal cells and are likely to grow and spread slowly; a higher Gleason score is likely to indicate a worse outcome. The Gleason score is used to help plan treatment and determine prognosis.
Time Frame	Screening and Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis set

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.
Measure Participants	3	3	10
Gleason Score at Screening	7.7 (1.2)	7.0 (0.0)	7.4 (0.7)
Gleason Score at Day 29	7.7 (1.2)	7.0 (0.0)	7.1 (0.9)

4. Secondary Outcome

Title	Percentage of Sample Considered Adenocarcinoma
Description	Tissues excised from the primary tumor during prostatectomy (Day 29) were evaluated for the percentage considered adenocarcinoma
Time Frame	Day 29 (prostatectomy)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.
Measure Participants	3	3	10
Primary Tumor at Screening	53.3 (5.8)	33.3 (24.7)	47.5 (22.0)
Primary Tumor at Day 29	25.0 (15.0)	56.7 (25.2)	42.5 (28.0)

5. Secondary Outcome

Title	Concentration of Paclitaxel in the Systemic Circulation
Description	Pharmacokinetic samples were taken on Day 1 at 1, 2, 4, and 6 hours post-injection, and weekly until prostatectomy. All numeric paclitaxel concentration data above the Lower Limit of Quantitation (25 pg/mL) was tabulated by cohort.
Time Frame	Day 1, Day 8, Day 15, Day 22, and Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume.
Measure Participants	3	3	10
Day 1 - 1 hr Post-Injection	5590.00 (2312.336)	19673.33 (20736.445)	19010.50 (15105.857)
Day 1 - 2 hr Post-Injection	3483.33 (1851.657)	9103.33 (7881.982)	12948.70 (10230.061)
Day 1 - 4 hr Post-Injection	2240.00 (756.241)	4740.00 (3889.884)	6830.80 (5219.617)
Day 1 - 6 hr Post-Injection	1926.67 (823.549)	5006.67 (4938.181)	5109.00 (3544.025)
Day 8	177.10 (102.777)	234.33 (73.446)	404.25 (221.326)
Day 15	65.10 (24.974)	82.85 (7.283)	106.11 (62.626)
Day 22	55.70 (15.556)	43.05 (16.051)	86.63 (52.358)
Day 29	35.45 (14.496)	54.75 (36.275)	57.64 (29.269)

6. Post-Hoc Outcome

Title	Change in PSA Density
Description	PSA density was measured with mpMRI
Time Frame	Screening and Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.
Measure Participants	3	3	10
PSA Density at Screening	3.64 (5.75)	0.23 (0.02)	0.31 (0.31)
PSA Density at Day 29	1.95 (2.84)	0.20 (0.01)	0.20 (0.11)

7. Post-Hoc Outcome

Title	Change in PI-RADS Score
Description	The Prostate Imaging Reporting and Data System (PI-RADS) assessment uses a five-point scale based on the probability that a combination of mpMRI findings on T2 weighting (T2W), Diffusion Weighted Imaging (DWI), and Dynamic Contrast Enhancement (DCE) correlates with the presence of a clinically significant cancer in the prostate gland. A PI-RADS score of 1 is considered to be most probably benign and a score of 5 is considered to be highly suspicious of a prostate malignancy. PI-RADS 1: very low (clinically significant cancer is highly unlikely to be present); PI-RADS 2: low (clinically significant cancer is unlikely to be present); PI-RADS 3: intermediate (presence of clinically significant cancer is equivocal); PI-RADS 4: high (clinically significant cancer is likely to be present); PI-RADS 5: very high (clinically significant cancer is highly likely to be present).
Time Frame	Screening and Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.
Measure Participants	3	3	10
PI-RADS 3 : Screening	1 33.3%	1 33.3%	1 10%
PI-RADS 3 : Day 29	0 0%	0 0%	2 20%
PI-RADS 4 : Screening	0 0%	1 33.3%	5 50%
PI-RADS 4 : Day 29	1 33.3%	2 66.7%	2 20%
PI-RADS 5 : Screening	2 66.7%	1 33.3%	4 40%
PI-RADS 5 : Day 29	2 66.7%	1 33.3%	6 60%

8. Post-Hoc Outcome

Title	Tumor Invasion Into Surrounding Tissues
Description	Assessed histologically after TRUS biopsy at Screening and on Day 29 prior to prostatectomy.
Time Frame	Screening and Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	NanoPac® 6 mg/mL	NanoPac® 10 mg/mL	NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.	NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume NanoPac®: Subjects with prostate cancer scheduled for prostatectomy will have NanoPac® injected intratumorally under image guidance directly into the lobe of the prostate with the dominant lesion 4 weeks prior to prostatectomy.
Measure Participants	3	3	10
Any invasion at Screening? Yes	2 66.7%	0 0%	4 40%
Any invasion at Screening? No	1 33.3%	3 100%	6 60%
Any invasion at Day 29? Yes	2 66.7%	2 66.7%	2 20%
Any invasion at Day 29? No	1 33.3%	1 33.3%	8 80%

Adverse Events

Time Frame	28 days, from Day 1 (the day of NanoPac injection) to Day 29 (the day of prostatectomy)
Adverse Event Reporting Description	Adverse events (AEs) were collected at all study visits from the time of dosing. Subjects were required to spontaneously report any AE. Study personnel asked open-ended questions to obtain information about AEs at every visit.
Arm/Group Title	NanoPac® 6 mg/mL		NanoPac® 10 mg/mL		NanoPac® 15 mg/mL
Arm/Group Description	NanoPac® 6 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.		NanoPac® 10 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.		NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume 4 weeks prior to prostatectomy.
All Cause Mortality
	NanoPac® 6 mg/mL		NanoPac® 10 mg/mL		NanoPac® 15 mg/mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/10 (0%)
Serious Adverse Events
	NanoPac® 6 mg/mL		NanoPac® 10 mg/mL		NanoPac® 15 mg/mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	NanoPac® 6 mg/mL		NanoPac® 10 mg/mL		NanoPac® 15 mg/mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		2/3 (66.7%)		6/10 (60%)
Blood and lymphatic system disorders
Anemia	2/3 (66.7%)	2	0/3 (0%)	0	1/10 (10%)	1
Leucocystosis	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Eye disorders
Vision Blurred	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Gastrointestinal disorders
Abdominal distension	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Abdominal Pain	2/3 (66.7%)	2	0/3 (0%)	0	0/10 (0%)	0
Constipation	1/3 (33.3%)	1	1/3 (33.3%)	1	0/10 (0%)	0
Diarrhoea	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Dry mouth	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Gastroesophageal reflux disease	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Ileus	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Nausea	2/3 (66.7%)	2	0/3 (0%)	0	2/10 (20%)	2
Procalgia	2/3 (66.7%)	2	0/3 (0%)	0	1/10 (10%)	1
Vomiting	0/3 (0%)	0	0/3 (0%)	0	2/10 (20%)	2
General disorders
Fatigue	3/3 (100%)	5	0/3 (0%)	0	0/10 (0%)	0
Local swelling	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Oedema peripheral	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Infections and infestations
Viral URTI	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0
Injury, poisoning and procedural complications
Procedural pain	0/3 (0%)	0	0/3 (0%)	0	4/10 (40%)	4
Wound complication	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	2/3 (66.7%)	2	0/3 (0%)	0	0/10 (0%)	0
Hperglycaemia	1/3 (33.3%)	1	0/3 (0%)	0	1/10 (10%)	1
Hypokalaemia	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)	2	0/3 (0%)	0	0/10 (0%)	0
Bone pain	1/3 (33.3%)	2	1/3 (33.3%)	1	0/10 (0%)	0
Myalgia	1/3 (33.3%)	2	0/3 (0%)	0	0/10 (0%)	0
Nervous system disorders
Dizziness	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Headache	0/3 (0%)	0	0/3 (0%)	0	2/10 (20%)	2
Lethargy	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Memory impairment	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Somnolence	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Tremor	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Psychiatric disorders
Anxiety	1/3 (33.3%)	1	1/3 (33.3%)	1	1/10 (10%)	1
Insomnia	1/3 (33.3%)	3	0/3 (0%)	0	0/10 (0%)	0
Renal and urinary disorders
Dysuria	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Haematuria	0/3 (0%)	0	1/3 (33.3%)	1	1/10 (10%)	1
Micturition urgency	1/3 (33.3%)	1	1/3 (33.3%)	1	0/10 (0%)	0
Nocturia	1/3 (33.3%)	1	1/3 (33.3%)	1	0/10 (0%)	0
Pollakiuria	1/3 (33.3%)	2	0/3 (0%)	0	0/10 (0%)	0
Urine flow decreased	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0
Vascular disorders
Hypertension	0/3 (0%)	0	1/3 (33.3%)	2	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.