Intravesical PPM Therapy for Bladder Cancer

Overseen By Lori Lerner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: VA Office of Research and Development

Must not be taking: Blood thinners

Disqualifiers: Upper urinary tract cancer, Metastasis, Heart failure, CNS disease, others

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

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new bladder cancer treatment called PPM (PLZ4-coated paclitaxel-loaded micelles). PPM uses tiny particles to deliver chemotherapy directly to cancer cells in the bladder. Researchers are studying PPM for patients whose bladder cancer has not responded to BCG treatment and does not invade the bladder's muscle layer. Patients diagnosed with bladder cancer in the last three months and who have experienced cancer recurrence despite past treatments might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use other investigational agents or certain medications that affect blood clotting, like aspirin (except low-dose), Coumadin, or heparin. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that a new treatment called PLZ4-coated paclitaxel-loaded micelles (PPM) has been tested in early studies for bladder cancer. These studies found that PPM can specifically target bladder cancer cells, delivering the chemotherapy drug paclitaxel directly to the tumor. This targeted approach aims to reduce side effects by focusing on cancer cells instead of healthy ones.

In these early studies, patients generally tolerated PPM well. Some mild side effects, common with chemotherapy drugs like paclitaxel, were reported. These side effects are usually manageable and temporary. Since this trial is in an early phase, the main goal is to find the safest dose and understand any potential risks. Overall, early results suggest PPM has a promising safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard bladder cancer treatments like surgery, chemotherapy, or immunotherapy, PLZ4-coated paclitaxel-loaded micelles (PPM) are delivered directly into the bladder. This unique delivery method allows for a higher concentration of the drug to reach the cancer cells with potentially fewer side effects since it's localized rather than systemic. Additionally, the PLZ4 coating helps the micelles target cancer cells more effectively, which could enhance the treatment's efficacy. Researchers are excited because this targeted approach might improve outcomes and reduce the treatment's impact on the rest of the body.

What evidence suggests that this treatment might be an effective treatment for bladder cancer?

Research has shown that a new treatment using PLZ4-coated paclitaxel-loaded micelles (PPM) can specifically target bladder cancer cells. This treatment delivers the chemotherapy drug paclitaxel directly into these cancer cells. In early animal tests, PPM showed promise in treating bladder cancer that hasn't spread into the muscle layer. Initial results suggest that PPM might help manage cancer unresponsive to another treatment called BCG. However, more research is needed to confirm its effectiveness in humans. Participants in this trial will receive PPM at varying doses to determine its efficacy and safety. ^{1 2 3 6 7}

Who Is on the Research Team?

Chong-Xian Pan, MD PhD

Principal Investigator

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Are You a Good Fit for This Trial?

This trial is for adults with bladder cancer that hasn't spread into the muscle and didn't respond to BCG treatment. Participants need good lung function, can't have severe heart issues or other serious illnesses, must not be pregnant or nursing, and should agree to use birth control. They should also have a life expectancy of more than 24 months.

Inclusion Criteria

I cannot or will not undergo major bladder surgery as advised.

I cannot or will not undergo major bladder surgery as advised.

Adherence to using a medically accepted method of birth control for female participants of childbearing potential and agreement for males to use barrier methods of birth control

Exclusion Criteria

Psychiatric illness/social situations that would limit compliance with study requirements

Other illness that in the opinion of the investigator would exclude the patient from participating in this study

I am not pregnant or nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

PPM is administered as intravesical instillation once weekly for six weeks to determine the recommended Phase II dose and assess toxicity and preliminary efficacy

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including urine cytology and cystoscopy

6 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PLZ4-coated paclitaxel-loaded micelles (PPM)

Trial Overview

The trial tests PLZ4-coated paclitaxel-loaded micelles (PPM), designed to target bladder cancer cells specifically. PPM will be placed directly into the bladder in patients who haven’t responded well to prior treatments. The study aims to find the right dose for future trials and check its safety and early effectiveness.

How Is the Trial Designed?

Group I: Phase I dose-escalation and expansion cohort Experimental Treatment 1 Intervention

There are three doses at the dose escalation stage: Dose level I: paclitaxel (PTX) 25 mg or 0.5 mg/ml; Dose Level II: PTX 50 mg or 1.0 mg/ml; Dose Level III: PTX 75 mg or 1.5 mg/ml. At the expansion cohort, up to 12 patients will be recruited and treated with PPM at the PTX dose of 50 mg or 1.0 mg/ml to determine the efficacy.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University of California, Davis

Collaborator

Trials

958

Recruited

4,816,000+

Published Research Related to This Trial

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]

The study developed mucoadhesive nanoparticles using hydrophobically derivatized hyperbranched polyglycerols (dHPGs) to deliver paclitaxel, showing that the HPG-C10-PEG formulation released up to 80% of the drug and remained stable in acidic urine, which is important for bladder cancer treatment.

In vivo tests demonstrated that the paclitaxel/HPG-C10-PEG formulation significantly reduced tumor growth in mice compared to standard Taxol, indicating its potential as a more effective and well-tolerated treatment for non-muscle-invasive bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy. Mugabe, C., Hadaschik, BA., Kainthan, RK., et al.[2018]

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]

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]

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]

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]

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]

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