Trial of NanoPac Focal Therapy for Prostate Cancer

Study Overview
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Brief Summary
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This study evaluates the use of NanoPac injected directly into the prostate lesion in men with prostate cancer.

Detailed Description
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NanoPac is very small (submicron) particles of the chemotherapy drug, paclitaxel, which is administered intravenously in a number of types of cancer. These submicron particles are injected directly into solid tumors to target cancer at the site of disease with less systemic exposure than intravenously administered chemotherapy. In this study, this submicron particle paclitaxel will be injected directly into the prostate lesion in men with prostate cancer scheduled for prostatectomy on up to three different occasions. All subjects in the study will receive NanoPac and will be evaluated to see if NanoPac is safe, well-tolerated, and has an impact on prostate cancer.

Official Title
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Phase 2 Trial of NanoPac Focal Therapy for Prostate Cancer in Subjects Undergoing Radical Prostatectomy

Conditions
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Prostate Cancer, Prostate Adenocarcinoma, Prostate Cancer Adenocarcinoma, Prostatic Neoplasm, Urogenital Neoplasms, Genital Neoplasms, Male, Localized Cancer

Intervention / Treatment
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* Drug: NanoPac (sterile nanoparticulate paclitaxel) Powder for Suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age; Histopathologically proven adenocarcinoma of the prostate: Localized cancer; Subjects with tumors classified as <T3 per TNM classification, Gleason score≥ 6; Prostate tumor must be able to be visualized on mpMRI; Already considered to be candidate for radical prostatectomy; Considered appropriate for treatment with paclitaxel therapy; 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 Calculated creatinine clearance ≥ 30 ml/min Normal PT/INR and PTT; ECOG of 0 or 1; International Prostate Symptom Score (I-PSS) less than or equal to 20; If sexually active, willing to use double condoms from time of NanoPac injection until prostatectomy; Agree to all study procedures and provide signed informed consent; Exclusion Criteria: Evidence of locally advanced or metastatic disease; Prostate size ≥ 50 cc; Prior prostatectomy, including surgery for any benign condition (such as TURP); 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) while on study prior to surgery; Treatment with a prior investigational medication within 30 days of first dose of study agent; Any previous local treatment of the prostate (e.g. radiation, HIFU, cryotherapy, Focal Irreversible Electroporation, Photodynamic Therapy, Laser Induced Thermometry); Any other condition (e.g., psychiatric disorder) that, in the opinion of the Investigator, may interfere with the subject's ability to comply with the study requirements or visit schedule; Known sensitivity to any of the study agent components; History of prior malignancy that has not been in remission for >5 years, with the exception of basal cell or squamous cell carcinoma.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single group, safety, efficacy, and pharmacokinetic study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NanoPac<br>Direct injection of NanoPac at 15 mg/mL at a volume not to exceed the volume of the prostate cancer lesion (no more than 10% of total prostate volume). NanoPac will be administered on up to three occasions, with at least 28 days between each dose. | Drug: NanoPac (sterile nanoparticulate paclitaxel) Powder for Suspension<br>* NanoPac is manufactured using a Precipitation with Compressed Antisolvent (PCA) technique that employs supercritical carbon dioxide and acetone to generate paclitaxel nanoparticles. For clinical administration, the NanoPac powder in vial is suspended with Sterile Reconstitution Solution (1% Polysorbate 80, NF in 0.9% Sodium Chloride for Injection, USP) and then further diluted with 0.9% Sodium Chloride for Injection, USP, to achieve the final clinical formulation.<br>* Other names: paclitaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events | Treatment emergent adverse events (including changes in laboratory assessments, physical examination findings, and vital signs) | Day 1 to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Based on Histologic Evaluation of Biopsied Prostate Samples (Gleason Score) | Prostate tissue samples obtained from a biopsy performed prior to baseline and prostatectomy. Histologic evaluation of these samples will be used to determine the Gleason score, and the results at baseline and Day 92 will be used to evaluate the tumor response to 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. | Up to 2 weeks prior to Day 1 and Day 92 | 
| Tumor Response Based on Change in Percentage of Sample Considered Adenocarcinoma | Tissues excised from the dominant lesion during prostatectomy (Day 92) will be evaluated for the percentage considered adenocarcinoma and compared to biopsy sample obtained at baseline. | Up to 2 weeks prior to Day 1 and Day 92 | 
| Tumor Invasion Into Surrounding Tissues | The proportion of subjects with local invasion as measured by mpMRI at the final study visit will be compared to screening (baseline) | Up to 1 month prior to Consent and Day 85 | 
| Tumor Response Based on Change in Image Volume on mpMRI | Tumor response to treatment with NanoPac will be determined by evaluating the change in image volume with multiparametric MRI (mpMRI) obtained prior to consent and again at the final study visit. | Up to 1 month prior to Consent and Day 85 | 
| Change in PSA Density | PSA density (PSAD), is a calculation of the serum PSA level divided by the volume of the prostate gland. PSA density has been used as a prognostication tool in helping decide treatment approach. PSA density measured at the final study visit will be compared to screening (baseline) | Up to 2 weeks prior to Day 1 and Day 85 | 
| Change in PI-RADS Score | 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 prostate malignancy. PI-RADS score will be measured at screening (baseline) and at the final study visit. | Up to 2 weeks prior to Day 1 and Day 85 | 
| Effect on Tumor Presence in Lymph Nodes | Optional PSMA PET scan performed prior to first NanoPac injection and prior to prostatectomy | Up to 2 weeks prior to Day 1 and Day 92 | 
| Concentration of Paclitaxel in the Systemic Circulation Post-injection | Pharmacokinetic samples will be obtained on days of NanoPac injection and other clinic visits. | Days 1, 8, 15, 29, 36, 43, 50, 57, 64, 71, and 85 | 
| Presence or Absence of Paclitaxel in Ejaculate | Ejaculate samples will be collected for analysis of the presence or absence of paclitaxel. | Days 15, 43, 57, and 85 | 
| Presence or Absence of Paclitaxel in Tissues Obtained at Prostatectomy | At the time of prostatectomy, available tissues including the tumor, the ipsilateral lobe of the prostate, the contralateral lobe of the prostate, and pelvic lymph nodes, will be evaluated for the presence or absence of paclitaxel | Day 92 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paclitaxel