Intravesical PPM Therapy for Bladder Cancer
Recruiting in Palo Alto (17 mi)
Overseen ByChong-Xian Pan, MD PhD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: VA Office of Research and Development
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial is testing a new bladder cancer treatment called PPM, which uses tiny particles to deliver a chemotherapy drug directly to cancer cells. It targets patients whose bladder cancer has not spread into the muscle and who did not respond to a previous treatment. The goal is to find the right dose and check for side effects and effectiveness.
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.
What data supports the effectiveness of the drug PLZ4-coated paclitaxel-loaded micelles (PPM) for bladder cancer?
Research shows that paclitaxel, when delivered using micelles (tiny particles that help carry drugs), can penetrate bladder tissues more effectively than traditional methods. This suggests that using PLZ4-coated paclitaxel-loaded micelles could improve drug delivery to bladder cancer cells, potentially making the treatment more effective.
12345Is PLZ4-coated paclitaxel-loaded micelles (PPM) safe for humans?
Research on paclitaxel-loaded polymeric micelles (PPM) in combination with cisplatin for lung cancer showed significant antitumor activity and improved tolerability compared to standard paclitaxel formulations, suggesting a favorable safety profile. However, specific safety data for PLZ4-coated PPM in humans is not available, and further research is needed to confirm its safety in clinical trials.
13567How is the drug PLZ4-coated paclitaxel-loaded micelles (PPM) unique for bladder cancer treatment?
PLZ4-coated paclitaxel-loaded micelles (PPM) are unique because they use a special coating to improve the delivery of paclitaxel directly into the bladder, enhancing drug uptake and effectiveness compared to traditional formulations. This approach helps the drug penetrate bladder tissues more effectively, potentially leading to better treatment outcomes for bladder cancer.
12346Eligibility Criteria
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.
My bladder cancer has not responded to BCG treatment or I cannot tolerate BCG.
I cannot or will not undergo major bladder surgery as advised.
I am 18 years old or older.
I have completed the recommended BCG treatment.
I am not currently undergoing, nor scheduled for, any cancer treatments.
My lungs work well and I don't have serious breathing problems.
My bladder cancer was confirmed by a biopsy within the last 3 months and a recent cystoscopy showed no deep muscle invasion.
I have recovered from any major side effects of previous treatments.
I can care for myself but may not be able to do active work.
Exclusion Criteria
I am not pregnant or nursing.
My cancer is located in the upper part of my urinary system.
I am currently on IV antibiotics for an infection.
I have a brain condition that cannot be controlled with treatment.
I have difficulty making decisions due to my health condition.
I have a bleeding disorder or take medication that affects blood clotting.
I have severe heart issues, including heart failure or irregular heartbeats.
My cancer has spread to other parts of my body.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Phase I dose-escalation and expansion cohortExperimental Treatment1 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MABoston, MA
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Who is running the clinical trial?
VA Office of Research and DevelopmentLead Sponsor
University of California, DavisCollaborator
References
The uptake of paclitaxel and docetaxel into ex vivo porcine bladder tissue from polymeric micelle formulations. [2018]Superficial bladder cancer occurs in the urothelial layer of the bladder and is usually treated by transurethral resection and chemotherapy. Although the bladder is well suited for intravesical chemotherapy, effective drug delivery is restricted by urine dilution and poor drug uptake by bladder tissues during a 2 h instillation. In this study, freshly excised pig bladder sections were mounted on Franz diffusion cells and treated with anticancer drugs paclitaxel (PTX) and docetaxel (DTX) formulated in diblock copolymer (methoxy poly(ethylene glycol)-block-poly (D,L-lactic acid) (MePEG-PDLLA) and methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-PCL) nanoparticles for 2 h. The bladder sections were then frozen, cryosectioned (60-μm sections) and the amount of (3)H drug taken up into each section was determined using liquid scintillation counting. Tissue concentration versus tissue depth profiles were obtained for all drug formulations and drug exposure obtained from area-under-the-curve (AUC) calculations. PTX or DTX loaded in MePEG-PDLLA micelles produced significantly higher urothelial tissue levels and greater bladder wall exposures compared to their commercial formulations, Cremophor EL/ethanol (PTX) or Tween 80 (DTX). The results of this study support the use of diblock copolymer micellar PTX or DTX formulations as they allow for improved drug penetration of bladder tissues compared to commercial formulations for taxane delivery to superficial bladder tumors.
Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy. [2018]The present report describes the development of paclitaxel-loaded gelatin nanoparticles for use in intravesical therapy of superficial bladder cancer. The commercial formulation of paclitaxel contains Cremophor, which forms micelles and thereby entraps the drug and reduces its partition across the urothelium.
Therapeutic effect of intravesical administration of paclitaxel solubilized with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) in an orthotopic bladder cancer model. [2018]To evaluate the effects of intravesical administration of paclitaxel (PTX-30W), which was prepared by solubilization with a water-soluble amphiphilic polymer composed of PMB30W, a copolymer of 2-methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate, in an orthotopic bladder cancer model.
Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy. [2018]To develop paclitaxel incorporated into unimolecular micelles based on hydrophobically derivatized hyperbranched polyglycerols (dHPGs) for use as mucoadhesive intravesical agents against non-muscle-invasive bladder cancer.
Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer. [2020]Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p
In vitro and in vivo evaluation of intravesical docetaxel loaded hydrophobically derivatized hyperbranched polyglycerols in an orthotopic model of bladder cancer. [2018]The objective of this study was to evaluate the tolerability, to establish a dosing regimen, and to evaluate the efficacy of intravesical docetaxel (DTX) formulations in a mouse model of bladder cancer. DTX in commercial formulation (Taxotere, DTX in Tween 80) or loaded in hyperbranched polyglycerols (HPGs) was evaluated. The synthesis and characterization of HPGs with hydrophobic cores and derivatized with methoxy poly(ethylene glycol) in the shell and further functionalized with amine groups (HPG-C(8/10)-MePEG and HPG-C(8/10)-MePEG-NH(2)) is described. Intravesical DTX in either commercial or HPGs formulations (up to 1.0 mg/mL) was instilled in mice with orthotopic bladder cancer xenografts and was well tolerated with no apparent signs of local or systemic toxicities. Furthermore, a single dose of intravesical DTX (0.5 mg/mL) loaded in HPGs was significantly more effective in reducing the tumor growth in an orthotopic model of bladder cancer than the commercial formulation of Taxotere. In addition, DTX-loaded HPG-C(8/10)-MePEG-NH(2) was found to be more effective at lower instillation dose than DTX (0.2 mg/mL)-loaded HPG-C(8/10)-MePEG. Overall, our data show promising antitumor efficacy and safety in a recently validated orthotopic model of bladder cancer. Further research is warranted to evaluate its safety and efficacy in early phase clinical trials in patients refractory to standard intravesical therapy.
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. [2015]The development of paclitaxel-loaded polymeric micelle (PPM) has circumvented many of the infusion-related difficulties associated with standard solvent-based paclitaxel. PPM plus cisplatin combination chemotherapy showed significant antitumor activity in phase I and II studies. This prospective randomized controlled phase IIB study assessed the noninferiority of the efficacy and tolerability of high-dose PPM plus cisplatin to a standard dose of paclitaxel plus cisplatin.