Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Adenocarcinoma

Prostatic Neoplasms

Urogenital Neoplasms

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

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.

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.

NanoPac (sterile nanoparticulate paclitaxel) Powder for Suspension

Shelagh Verco, PhD

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

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.

Open-label, single group, safety, efficacy, and pharmacokinetic study.

Trial of NanoPac Focal Therapy for Prostate Cancer

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

Treatment emergent adverse events (including changes in laboratory assessments, physical examination findings, and vital signs)

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.

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.

The proportion of subjects with local invasion as measured by mpMRI at the final study visit will be compared to screening (baseline)

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.

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)

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.

Optional PSMA PET scan performed prior to first NanoPac injection and prior to prostatectomy

Pharmacokinetic samples will be obtained on days of NanoPac injection and other clinic visits.

Ejaculate samples will be collected for analysis of the presence or absence of paclitaxel.

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

US Biotest, Inc.

NanOlogy, LLC

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.

NanoPac (sterile nanoparticulate paclitaxel) Powder for Suspension: 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.

NanoPac

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study was terminated early due to lack of enrollment.

Gere S. diZerega, MD

Number of Participants With Treatment Emergent Adverse Events

Tumor Response Based on Histologic Evaluation of Biopsied Prostate Samples (Gleason Score)

Tumor Response Based on Change in Percentage of Sample Considered Adenocarcinoma

Tumor Invasion Into Surrounding Tissues

Tumor Response Based on Change in Image Volume on mpMRI

Change in PSA Density

Change in PI-RADS Score

Effect on Tumor Presence in Lymph Nodes

Concentration of Paclitaxel in the Systemic Circulation Post-injection

Presence or Absence of Paclitaxel in Ejaculate

Presence or Absence of Paclitaxel in Tissues Obtained at Prostatectomy

Overall Study

Symptoms and General Pathology

Behaviors and Mental Disorders

Neoplasm Metastasis

Body Weight

Quality of Life

All consecutive patients with a histologically confirmed diagnosis of solid tumor referred to any of the Medical Oncology Units of the S.I.C.O.G. cooperative group (http://www.sicog.it/).

Vincenzo Formica, MD, PhD

Cristiano Serci

Mario Roselli

BMI is a simple and widely recorded variable that may capture obesity or cachexia in cancer patients. How BMI is associated to health-related quality of life (HR-QoL) in such patients is poorly investigated.

High BMI may be associated to obesity, an increased burden of comorbidity, reduced physical activity and, in some settings, to more aggressive oncological disease. On the other hand, low BMI may reflect enhanced weight loss, cachectic syndrome, higher tumor burden and adverse prognostic features which all deteriorate quality of life. The aim of the present study is to evaluate the association of BMI and HR-QoL as measured by the EORTC-QLQ-C30 questionnaire in several cancer settings (such as localized vs metastatic or distinct primary tumors).

Health-related quality of life (HRQoL) might have varied association to body weight in patients with solid cancer\[1\].

On one hand low body weight may reflect cancer-related anorexia and weight loss and cachectic syndrome which are associated to impaired performance status, deteriorated general conditions and advanced cancer\[2\]. In such patients the probability of recording a low Body Mass Index (BMI) and concomitantly an inferior Health related quality of life (HRQoL, as patient reported outcome, PRO) is high.

On the other hand, some of the hormonal mediators found at increased concentration in obese patients, such as insulin-like growth factor (IGF), have been demonstrated to be involved in biological pathways that favor an improved HRQoL\[3\].

Adding further apparent contradiction is the fact that obesity and high BMI may represent in some cancer settings an adverse feature. In particular, obesity is associated with an increased risk of developing certain tumor types and, in some cancer patients with radically resected primary, of cancer relapse\[4\]. Moreover high BMI carries often an increased burden of comorbidity (e.g. cardiovascular and metabolic diseases)\[5\] and reduced physical activity. All these factors may reduce HRQoL.

Studies investigating specific associations between BMI and HRQoL in specific cancer settings are therefore warranted.

The present prospective observational cohort study has the aim of investigating the relationship between BMI and PRO-HRQoL as measured by the EORTC-QLQ-C30 questionnaire \[6\] in different primary tumors (breast, lung, colorectal and others) and in different cancer stages (localized vs metastatic). Patients will be also stratified according to the presence of cardiovascular and metabolic comorbidities, to the Karnofsky Performance status and according to the oncological treatment received (chemotherapy vs radically resected patients on follow-up). If available, retrospective data will be used to train possible predictive models.

STUDY PROCEDURES Study participation will be offered to all consecutive patients with a histologically confirmed diagnosis of solid tumor referred to the Medical Oncology Units of the S.I.C.O.G. cooperative group (http://www.sicog.it/). Upon acceptance, patients will sign an informed consent and be asked to fill out the EORTC QLQ C30 questionnaire.

All common antropometric, demographic, clinical and biochemical variables will be recorded around the moment of first referral (within three months).

Re-assessable variables, including EORTC QLQ-C30 questionnaire re-administration, will be recorded every 4-6 months thereafter. All data will be stored in a prospectively maintained database.

Among recorded data will be: age, sex, weight, height, occupation, civil status, primary tumor site, tumor stage, possible metastatic sites, past and actual type of oncological treatment, pain score, Karnofsky Performance Status, vital signs, routine blood tests Patients will be oncologically managed according to standard practice Association between BMI and EORTC QLQ-C30 will be assesses using regression analyses across the different clinical settings identified.

STATISTICAL CONSIDERATIONS The design of the study hypothesizes that in metastatic patients an improved HR-QoL is associated with high BMI (non-cachectic patients) An 'exact single-stage design' will be followed \[7\]. According to historical data (endometrial cancer), 50% of patients with BMI \< 30 has a high global health status score (GHS) of the EORTC QLQ C30 (i.e. a GHS score ≥ 80%) \[8\].

The hypothesis to be tested will be H0, P \< P0 vs H1, P \> P1, where P is the percentage of patients with GHS ≥ 80%. One-tail alpha error of 0.05 and false-negative (beta) rate of 0.2 will be considered. P0 will be set at 50% and P1 at 65%, looking for a 15% increase in the percentage of high GHS score among patients with BMI \>30. The H0 hypothesis will be rejected and H1 accepted with a statistical power of 80% if at least 42 patients out of 69 with BMI \> 30 will report a GHS score ≥ 80.

Since BMI \> 30 is observed in about 10% of all metastatic patients, a total of 690 metastatic patients will be required. Since metastatic patients are about half of all cancer patients referred to Medical Oncology Units, a final sample size of 1380 cancer patients (all stages) will be set as the target number.

Body Mass Index (BMI) and Quality of Life (QoL) in Cancer Patients

To assess the relationship between BMI and EORTC-QLQC30 scores in localized vs metastatic cancer patients

- To assess the relationship between BMI and EORTC-QLQC30 scores according to:

* primary tumor
* presence vs absence of cardiovascular and/or metabolic comorbidities
* Performance status
* Ongoing chemotherapy treatment vs observation in disease-free patients (follow-up)
* Other clinical and biochemical variables routinely assessed as common practice

S.I.C.O.G. partners

University of Rome Tor Vergata

Consultant in Medical Oncology, Principal Investigator

Rare Diseases

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Transitional Cell Carcinoma

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Cycles 1-2 (Pembrolizumab): 400 mg of Pembrolizumab intravenously (Administered Day 1 of 42 day Cycle)

If complete response of treatment is observed then maintenance therapy will be given. All other patients will receive with standard of care local therapy (cystectomy or chemo-radiation) as per their treating physicians followed by "adjuvant" pembrolizumab.

Cycle 3-9 (Maintenance or Adjuvant Single agent Pembrolizumab): 400 mg of Pembrolizumab intravenously (Administered Day 1 of 42 day Cycle)

Matthew D Galsky, MD

Arhan Lee

Hesham Mahmoud

Sumanta Pal, MD

Marietta Moore

Stacy Moore

Jennifer King, MD

Jessica White

Neda Hashemi Sadraei, MD

Patricia Acon

Matthew Galsky, MD

Subjects with cT2-T3N0M0 urothelial cancer of the bladder will be enrolled. After completing two cycles of pembrolizumab, subjects will undergo a restaging MRI of the abdomen and pelvis with a standard acquisition protocol (as outlined in the protocol) as well as CT chest. A CT of the abdomen and pelvis may be performed if there are contraindications to MRI. Patients will also undergo a restaging cystoscopy and biopsies/TURBT as outlined in the protocol.

Patients achieving a clinical complete response to treatment (defined in the protocol) will proceed with "maintenance" single agent pembrolizumab followed by surveillance. All other patients will proceed with standard of care local therapy as per their treating physicians followed by "adjuvant" pembrolizumab.

Pembrolizumab in Muscle-invasive Bladder Cancer

Neoadjuvant Pembrolizumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing

Estimate the clinical complete response rate defined as cT0 or cTa disease after pembrolizumab

Estimate the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment. For patients achieving a clinical complete response, benefit will be defined as 2 year metastasis-free survival in patients among the patients achieving a clinical complete response.

Describe the safety of neoadjuvant pembrolizumab.Safety will be determined according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5

Positive predictive value of PD-L1 CPS, in predicting benefit from treatment in patients achieving a clinical complete response. Combined Positive Score (CPS) is defined as the number of PD-L1 staining cells divided by the total number of viable tumor cells, multiplied by 100.

Positive predictive value of TMB in predicting benefit from treatment in patients achieving a clinical complete response. Tumor mutational burden (TMB) is defined as the total number of somatic nonsynonymous mutations per coding area of a tumor genome.

Estimate metastasis free survival in the overall study population. Metastasis-free survival is defined as the time from initiation of treatment to the development of metastatic disease. Microscopic metastatic disease involving regional lymph nodes resected at cystectomy performed with curative intent will not be considered an event. Confirmation of metastatic recurrence with a biopsy is recommended in all situations.

Estimate the 2 year metastasis-free survival. Metastasis-free survival is defined as the time from initiation of treatment to the development of metastatic disease. Microscopic metastatic disease involving regional lymph nodes resected at cystectomy performed with curative intent will not be considered an event. Confirmation of metastatic recurrence with a biopsy is recommended in all situations.

Estimate metastasis free survival in patients achieving a clinical complete response. Metastasis-free survival is defined as the time from initiation of treatment to the development of metastatic disease. Microscopic metastatic disease involving regional lymph nodes resected at cystectomy performed with curative intent will not be considered an event. Confirmation of metastatic recurrence with a biopsy is recommended in all situations.

Estimate metastasis free survival in patients not achieving a clinical complete response. Metastasis-free survival is defined as the time from initiation of treatment to the development of metastatic disease. Microscopic metastatic disease involving regional lymph nodes resected at cystectomy performed with curative intent will not be considered an event. Confirmation of metastatic recurrence with a biopsy is recommended in all situations.

Bladder-intact event-free survival is defined from initiation of treatment until radical cystectomy, evidence of unresectable or metastatic disease, or death due to any cause.

Estimate bladder-intact event free survival in patients achieving a clinical complete response. Bladder-intact event-free survival is defined from initiation of treatment until radical cystectomy, evidence of unresectable or metastatic disease, or death due to any cause.

Estimate bladder-intact event free survival in patients not achieving a clinical complete response. Bladder-intact event-free survival is defined from initiation of treatment until radical cystectomy, evidence of unresectable or metastatic disease, or death due to any cause.

Estimate overall survival. Overall survival is defined as the time from initiation of treatment to death.

Estimate overall survival in patients achieving a clinical complete response. Overall survival is defined as the time from initiation of treatment to death.

Estimate overall survival in patients not achieving a clinical complete response. Overall survival is defined as the time from initiation of treatment to death.

Estimate bladder-intact overall survival. Bladder-intact overall survival is defined as the time from initiation of treatment until death or cystectomy.

Estimate bladder-intact overall survival in patients achieving a clinical complete response. Bladder-intact overall survival is defined as the time from initiation of treatment until death or cystectomy.

Estimate bladder-intact overall survival in patients not achieving a clinical complete response. Bladder-intact overall survival is defined as the time from initiation of treatment until death or cystectomy.

Estimate invasive bladder recurrence-free survival in patients achieving a clinical complete response and in all patients not undergoing cystectomy. Invasive bladder recurrence free survival will be defined as the time from initiation of treatment to the development of at least cT/pT1 urothelial cancer in the bladder.

Estimate the RFS. Recurrence-free survival is defined as the time from initiation of treatment to death or recurrence, depending on which occurs first.

Estimate the RFS in patients achieving a clinical complete response. Recurrence-free survival is defined as the time from initiation of treatment to death or recurrence, depending on which occurs first.

Estimate the RFS in patients not achieving a clinical complete response. Recurrence-free survival is defined as the time from initiation of treatment to death or recurrence, depending on which occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of NanoPac Focal Therapy for Prostate Cancer	NCT04221828	Prostate Cancer Prostate Adenoc... Prostate Cancer... Prostatic Neopl... Urogenital Neop... Genital Neoplas... Localized Cance...	NanoPac (steril...	18 Years -	NanOlogy, LLC
Body Mass Index (BMI) and Quality of Life (QoL) in Cancer Patients	NCT03873064	Neoplasm Malign... Body Weight Quality of Life		18 Years -	University of Rome Tor Vergata
Pembrolizumab in Muscle-invasive Bladder Cancer	NCT05406713	Muscle Invasive... Localized Cance... Urothelial Carc...	Pembrolizumab	18 Years -	Hoosier Cancer Research Network

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