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| Name | Class |
|---|---|
| US Biotest, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NanoPac® 6 mg/mL | Experimental | 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 | Experimental | 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 | Experimental | NanoPac® 15 mg/mL injected into the prostate lobe containing the dominant lesion at a volume of 20% prostate lobe volume |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NanoPac® | Drug | 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 | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | Treatment Emergent Adverse Events included laboratory assessments, physical examination findings, and vital signs. | Day 1 to Day 29 |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Response Based on Change in Image Volume on mpMRI | 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. |
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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:
Willing to use appropriate contraception from time of NanoPac® injection until prostatectomy
Willing to receive an mpMRI
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shelagh Verco, PhD | US Biotest, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California | Los Angeles | California | 90033 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 4 weeks prior to prostatectomy. |
| FG001 | 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 4 weeks prior to prostatectomy. |
| FG002 | 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 4 weeks prior to prostatectomy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 4 weeks prior to prostatectomy. |
| BG001 | NanoPac® 10 mg/mL |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment Emergent Adverse Events (Safety and Tolerability) | Treatment Emergent Adverse Events included laboratory assessments, physical examination findings, and vital signs. | Full Analysis Set | Posted | Count of Participants | Participants | Day 1 to Day 29 |
|
28 days, from Day 1 (the day of NanoPac injection) to Day 29 (the day of prostatectomy)
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 4 weeks prior to prostatectomy. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 20.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gere S. diZerega, MD | NanOlogy, LLC | 805-595-1300 | gere.dizerega@usbiotest.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 8, 2017 | May 1, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 13, 2018 | May 1, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D011469 | Prostatic Diseases |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
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| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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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.
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|
| Up to three months prior to consent and Day 29 |
| Tumor Response Based on Histologic Evaluation of Biopsied Prostate Samples (Gleason Score) | 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. | Screening and Day 29 |
| Percentage of Sample Considered Adenocarcinoma | Tissues excised from the primary tumor during prostatectomy (Day 29) were evaluated for the percentage considered adenocarcinoma | Day 29 (prostatectomy) |
| Concentration of Paclitaxel in the Systemic Circulation | 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. | Day 1, Day 8, Day 15, Day 22, and Day 29 |
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.
| BG002 | 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 4 weeks prior to prostatectomy. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
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. |
| OG002 | 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 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. |
|
|
| Secondary | Tumor Response Based on Change in Image Volume on mpMRI | 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. | Full Analysis Set | Posted | Mean | Standard Deviation | cc | Up to three months prior to consent and Day 29 |
|
|
|
| Secondary | Tumor Response Based on Histologic Evaluation of Biopsied Prostate Samples (Gleason Score) | 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. | Full Analysis set | Posted | Mean | Standard Deviation | score on a scale | Screening and Day 29 |
|
|
|
| Secondary | Percentage of Sample Considered Adenocarcinoma | Tissues excised from the primary tumor during prostatectomy (Day 29) were evaluated for the percentage considered adenocarcinoma | Full Analysis Set | Posted | Mean | Standard Deviation | percentage of sample adenocarcinoma | Day 29 (prostatectomy) |
|
|
|
| Secondary | Concentration of Paclitaxel in the Systemic Circulation | 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. | Full Analysis Set | Posted | Mean | Standard Deviation | Plasma paclitaxel concentration (pg/mL) | Day 1, Day 8, Day 15, Day 22, and Day 29 |
|
|
|
| Post-Hoc | Change in PSA Density | PSA density was measured with mpMRI | Full Analysis Set | Posted | Mean | Standard Deviation | ng/mL/cc | Screening and Day 29 |
|
|
|
| Post-Hoc | 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 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). | Full Analysis Set | Posted | Count of Participants | Participants | Screening and Day 29 |
|
|
|
| Post-Hoc | Tumor Invasion Into Surrounding Tissues | Assessed histologically after TRUS biopsy at Screening and on Day 29 prior to prostatectomy. | Full Analysis Set | Posted | Count of Participants | Participants | Screening and Day 29 |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | 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 4 weeks prior to prostatectomy. | 0 | 3 | 0 | 3 | 2 | 3 |
| EG002 | 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 4 weeks prior to prostatectomy. | 0 | 10 | 0 | 10 | 6 | 10 |
| Leucocystosis | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vision Blurred | Eye disorders | MedDRA 20.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Procalgia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Local swelling | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Viral URTI | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Wound complication | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hperglycaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Urine flow decreased | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 20.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
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| D000091642 |
| Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
|
|
|
|
| Day 1 - 4 hr Post-Injection |
|
| Day 1 - 6 hr Post-Injection |
|
| Day 8 |
|
| Day 15 |
|
| Day 22 |
|
| Day 29 |
|
|
| Title | Measurements |
|---|---|
|
| PI-RADS 4 : Screening |
|
| PI-RADS 4 : Day 29 |
|
| PI-RADS 5 : Screening |
|
| PI-RADS 5 : Day 29 |
|
|
| Any invasion at Day 29? Yes |
|
| Any invasion at Day 29? No |
|