PPM for Bladder Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mamta Parikh

Must not be taking: Anticoagulants, Direct thrombin inhibitors

Disqualifiers: Upper urinary tract cancer, Metastasis, Severe cardiac dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 6 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PLZ4-coated paclitaxel-loaded micelles (PPM) for individuals with bladder cancer that hasn't responded to other treatments or has recurred. The goal is to determine the safety and effectiveness of this treatment. PPM is designed to deliver cancer-fighting medicine directly to the tumor cells in the bladder. Individuals with non-muscle invasive bladder cancer that hasn't responded to Bacillus Calmette-Guerin (BCG) treatment or who cannot undergo major surgery might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot have concurrent radiotherapy, chemotherapy, or other immunotherapy for bladder cancer. Also, certain blood-thinning medications like aspirin (except low-dose), Coumadin, and heparin must be stopped before therapy.

Is there any evidence suggesting that PLZ4-coated paclitaxel-loaded micelles (PPM) are likely to be safe for humans?

Research shows that a new treatment using PLZ4-coated paclitaxel-loaded micelles (PPM) could be effective against bladder cancer. Early studies have demonstrated that PPM can deliver the cancer-fighting drug paclitaxel directly to cancer cells. This targeted method aims to attack the tumor while sparing healthy cells, potentially resulting in fewer side effects.

Since this treatment is just beginning human trials, limited safety information is available. However, its testing in humans indicates that earlier lab and animal tests showed sufficient promise and safety to proceed. These early trials focus on how well participants tolerate the treatment and monitor for any unwanted effects. Participants will be closely observed for side effects or any signs of poor tolerance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment options for bladder cancer, which typically include surgery, chemotherapy, and immunotherapy, PLZ4-coated paclitaxel-loaded micelles (PPM) offer a unique approach. This treatment is intriguing because it uses a special coating (PLZ4) to deliver paclitaxel directly to the bladder via intravesical administration, potentially enhancing the drug's effectiveness while minimizing side effects. The coating helps the drug specifically target cancer cells, which could lead to more efficient treatment with fewer adverse reactions. Researchers are excited because this targeted delivery method may improve outcomes for patients by directly attacking cancer cells where they reside, reducing the likelihood of progression or recurrence.

What evidence suggests that PLZ4-coated paclitaxel-loaded micelles might be an effective treatment for bladder cancer?

Research has shown that a new treatment using PLZ4-coated paclitaxel-loaded micelles (PPM), which participants in this trial will receive, could be promising for bladder cancer. In early studies, PPM specifically targeted bladder cancer cells and delivered the drug paclitaxel directly to them. This targeted delivery allows more of the drug to reach the cancer cells, potentially killing them or stopping their growth. Studies also suggest that these micelles can assist in both detecting and treating bladder cancer, highlighting their potential for future use. While more research is needed, these early results indicate that PPM could effectively treat non-muscle invasive bladder cancer that recurs or resists other treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Mamta Parikh

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for people with non-muscle invasive bladder cancer that has either returned after getting better or hasn't responded to other treatments. Participants should meet specific health criteria not detailed here.

Inclusion Criteria

Total bilirubin ≤ 2.0 × institutional upper limit of normal (ULN) (< 3 × ULN for patients with Gilbert's syndrome)

Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) ≤ 3.0 × institutional ULN

I am not currently receiving any treatments for bladder cancer.

Exclusion Criteria

I do not have uncontrollable brain or nerve disease.

I am not pregnant or breastfeeding.

Any condition that would prohibit the understanding or rendering of informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive PPM intravesically over 1 hour once a week for 6 weeks

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

3 visits (in-person) at 3 weeks, 6 weeks, and then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• PLZ4-coated paclitaxel-loaded micelles (PPM)

Trial Overview The trial is testing the safety and effectiveness of a new treatment called PPM, which targets tumor cells in the bladder using nanoparticles containing paclitaxel, a drug known to inhibit tumor growth.

How Is the Trial Designed?

Group I: PLZ4-coated paclitaxel loaded micelles (PPM) Experimental Treatment 1 Intervention

Patients receive PPM intravesically over 1 hour QW for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, or PET, and cystoscopy with biopsy at screening and follow up and undergo collection of blood samples throughout the trial.

Who Is Running the Clinical Trial?

Mamta Parikh

Lead Sponsor

Trials

7

Recruited

210+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Paclitaxel-loaded gelatin nanoparticles were developed for treating superficial bladder cancer, showing a rapid drug release profile with approximately 90% of the drug released within 2 hours, making them a promising option for intravesical therapy.

In a study involving dogs, these nanoparticles achieved drug concentrations in bladder tissues that were 2.6 times higher than those obtained with the conventional Cremophor formulation, indicating improved delivery and potential efficacy against bladder tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy. Lu, Z., Yeh, TK., Tsai, M., et al.[2018]

In a phase IIB study involving 276 patients with advanced non-small-cell lung cancer, paclitaxel-loaded polymeric micelles (PPM) combined with cisplatin demonstrated a response rate of 43.6%, which was noninferior to the 41.9% response rate of standard paclitaxel plus cisplatin.

While PPM plus cisplatin had a higher incidence of grade 3 neutropenia, the overall safety profile was comparable to that of the standard treatment, indicating that PPM is a well-tolerated alternative for chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-loaded polymeric micelle (230 mg/m(2)) and cisplatin (60 mg/m(2)) vs. paclitaxel (175 mg/m(2)) and cisplatin (60 mg/m(2)) in advanced non-small-cell lung cancer: a multicenter randomized phase IIB trial. Lee, SY., Park, HS., Lee, KY., et al.[2015]

Targeting micelles decorated with the bladder cancer-specific ligand PLZ4 showed significantly improved drug delivery and cell-killing efficiency in dog bladder cancer cells compared to nontargeting micelles, indicating their potential as effective therapeutic agents.

In vivo studies demonstrated that PLZ4-targeted micelles delivered drugs 14.3 times more efficiently than free dye and 1.5 times more efficiently than nontargeting micelles, suggesting a promising approach for targeted cancer treatment in dogs that could be translated to human applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer. Lin, TY., Zhang, H., Luo, J., et al.[2021]

Diblock copolymer micelles (MePEG-PDLLA and MePEG-PCL) significantly enhance the delivery of anticancer drugs paclitaxel (PTX) and docetaxel (DTX) into bladder tissues compared to traditional commercial formulations, leading to higher tissue levels and better drug exposure.

This study utilized freshly excised pig bladder sections and demonstrated that these micellar formulations improve drug penetration, suggesting a more effective treatment option for superficial bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The uptake of paclitaxel and docetaxel into ex vivo porcine bladder tissue from polymeric micelle formulations. Tsallas, A., Jackson, J., Burt, H.[2018]

Targeting micelles decorated with bladder cancer-specific ligands significantly improved the delivery of the chemotherapeutic drug paclitaxel to bladder cancer cells, showing better efficacy in both lab tests and in mice with patient-derived tumors.

The micelle formulation of paclitaxel was less toxic than traditional formulations, allowing for a higher dose to be administered without increasing side effects, and it effectively controlled cancer growth and extended survival in treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeting multifunctional micelles for imaging and chemotherapy of advanced bladder cancer. Lin, TY., Li, YP., Zhang, H., et al.[2021]

The study developed a novel bladder cancer-targeting nanomicelle (DC-PNM) that effectively delivers the chemotherapy drug paclitaxel (PTX), showing a significant improvement in survival rates in mice with bladder cancer xenografts, increasing median survival from 55 days to 69.5 days.

DC-PNM demonstrated specific targeting to bladder cancer cells while showing minimal interaction with lung cancer cells, indicating its potential for reducing toxicity and enhancing the efficacy of chemotherapy in treating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer. Pan, A., Zhang, H., Li, Y., et al.[2020]

Intravesical administration of paclitaxel formulated with the PMB30W polymer (PTX-30W) showed no cytotoxicity in cell cultures, unlike the conventional solubilizer Cremophor, which was toxic to bladder cancer cells.

In an orthotopic bladder cancer model, PTX-30W significantly reduced tumor weight and achieved higher paclitaxel concentrations in tumors compared to the Cremophor formulation, suggesting better efficacy and penetration for treating non-muscle invasive bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of intravesical administration of paclitaxel solubilized with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) in an orthotopic bladder cancer model. Tamura, K., Kikuchi, E., Konno, T., et al.[2018]

Intravesical docetaxel (DTX) formulations, particularly those loaded in hyperbranched polyglycerols (HPGs), were well tolerated in a mouse model of bladder cancer, showing no significant local or systemic toxicities.

The HPG-loaded DTX formulation (0.5 mg/mL) was significantly more effective in reducing tumor growth compared to the commercial formulation (Taxotere), indicating a potential for improved efficacy in bladder cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo evaluation of intravesical docetaxel loaded hydrophobically derivatized hyperbranched polyglycerols in an orthotopic model of bladder cancer. Mugabe, C., Matsui, Y., So, AI., et al.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.806

A phase I first-in-human clinical trial with PLZ4-coated ... Our preclinical data has demonstrated PPM can selectively target bladder cancer cells and deliver paclitaxel payload into these cancer cells ...

2. bcan.org bcan.org/clinicaltrials/plz4-coated-paclitaxel-loaded-micelles-for-the-treatment-of-patients-with-recurrent-or-refractory-non-muscle-invasive-bladder-cancer/

PLZ4-Coated Paclitaxel-Loaded Micelles for the Treatment ... This phase I trial tests the safety, tolerability and effectiveness of PLZ4-coated paclitacel-loaded micelles (PPM) in treating patients with non-muscle ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05519241

Study Details | NCT05519241 | A Phase I Intravesical PPM ... PLZ4 is a molecule that can possibly guide PPM to specifically target and deliver paclitaxel into and kill bladder cancer cells. In this trial, PPM will be ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3664656/

Tumor-targeting multifunctional micelles for imaging and ... Targeting micelles loaded with paclitaxel offer strong potential for clinical applications in treating bladder cancer.

5. asco.org asco.org/abstracts-presentations/ABSTRACT418100

A phase I dose-escalation clinical trial with PLZ4-coated ... Despite combination treatment, 20-80% of patients' disease recurs and 25% progress to invasive stages. The study drug, PLZ4-coated paclitaxel-loaded micelle ( ...

6. bcan.org bcan.org/clinicaltrials/intravesical-ppm-therapy-for-nmibc/

Intravesical PPM Therapy for NMIBC This clinical trial is to determine the safety and effectiveness of an investigational bladder cancer drug named "PLZ4-coated paclitaxel-loaded nanoscale ...

7. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2025.43.5_suppl.806

A phase I first-in-human clinical trial with PLZ4-coated ... Our preclinical data has demonstrated PPM can selectively target bladder cancer cells and deliver paclitaxel payload into these cancer cells following ...