Trial of NanoPac® Focal Therapy in Subjects With Prostate Cancer

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.

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.