Non-muscle-invasive Bladder CancerPhase 1NCT05519241
A Phase I Intravesical PPM Therapy for NMIBC
A Phase 1 study testing PLZ4-coated paclitaxel-loaded micelles (PPM) in people with Non-muscle-invasive Bladder Cancer, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This clinical trial is to determine the safety and effectiveness of an investigational bladder cancer drug named "PLZ4-coated paclitaxel-loaded nanoscale micelle (PPM)." PPM is tiny particles that contain the chemotherapy drug paclitaxel. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-muscle-invasive Bladder Cancer
- What is being tested?
- PLZ4-coated paclitaxel-loaded micelles (PPM)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2022to 31 Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following criteria to be eligible for study entry.
- Histologically confirmed bladder carcinoma in situ (CIS) urothelial or urothelial carcinoma, with or without T1 cancer. Patients are eligible if the biopsy was done within 3 months of enrollment and a cystoscopy demonstrates no gross disease invasion into muscularis propria within 4 weeks of enrollment.
- Patient must have BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) or intolerance of treatment with BCG. Treatment of pembrolizumab is not an inclusion or exclusion criteria as intravesical taxane probably has comparable efficacy as intravenous pembrolizumab. BCG-unresponsive disease is defined as being at least one of the following:
- Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy
- Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy
- T1 high-grade disease at the first evaluation following an induction BCG course
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- In this context, adequate BCG therapy is defined as at least one of the following:
- At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy
- At least five of six doses of an initial induction course plus at least two of six doses of a second induction course
- Refuse or intolerant of a radical cystectomy recommended by the treating urologist as the standard next therapy per urologic guidelines
- Performance status: ECOG performance status of 0, 1, or 2 or Karnofsky performance status of 50 or higher
- Patient with life expectancy greater than 24 months
- No concurrent radiotherapy, chemotherapy, or other immunotherapy
- No scheduled radiotherapy, chemotherapy, other immunotherapy, or surgery before the scheduled response evaluation
- Recovery from prior treatment side effects that might interfere with the study treatment, in the judgment of the participating urologist
- Laboratory tests performed within 14 days of study enrollment:
- Absolute neutrophil count (AGC/ANC)1,500/uL
- Platelets100,000/uL [Patients may be transfused to meet this requirement]
- Hemoglobin 8 g/dL [Patients may be transfused to meet this requirement]
- Calculated glomerular filtration rate (GFR) 50 mL/min/1.73m2
- Total bilirubin 2.0 X ULN (< 3 x ULN for patients with Gilbert's syndrome)
- AST, ALT, ALP 3.0 X ULN
- Adequate pulmonary function with no clinical signs of severe pulmonary dysfunction
- Negative serum pregnancy test if the study participant is a female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized)
- Female participants of childbearing potential must adhere to using a medically accepted method of birth control, i.e. a tubal ligation, an approved hormonal contraceptive or an intrauterine device, prior to screening and agree to continue its use during the study and up to 3 months after finishing this study or be surgically sterilized (e.g., hysterectomy or tubal ligation). Males must agree to use barrier methods of birth control while on study
- Provide signed informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations
Who cannot join
- Patients who meet any of the following criteria will be excluded from study entry.
- Existence of cancer at the upper urinary tract
- Concurrent use of other investigational agents
- Evidence of regional and/or distant metastasis
- NYHA (New York Heart Association) Class III or IV heart failure, uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, or other clinical signs of severe cardiac dysfunction
- Symptomatic congestive heart failure (CHF), severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry
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- Patient has an intractable bleeding disorder (e.g., coagulation factors deficiencies, Von Willebrand Disease)
- Patient taking medications that affect coagulation, such as aspirin (aspirin 81 mg oral once daily is allowed), Coumadin/Warfarin, heparin, low molecular weight heparin, direct thrombin inhibitors, and direct factor Xa inhibitors. Other nonsteroidal anti-inflammatory drugs (NSAIDs) are allowed as long as they are discontinued the day before therapy.
- History or evidence of uncontrollable central nervous system (CNS) disease
- Active systemic infection requiring parenteral antibiotic therapy.
- Women who are pregnant or nursing
- 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
- Any other malignancy diagnosed within 3 years of trial entry with the exception of:
- Basal or squamous cell skin cancers, or
- Noninvasive cancer of the cervix, or
- Any other cancer deemed to be of low-risk for progression or patient morbidity during trial period, such as localized prostate cancer after definitive treatment and prostate-specific antigen (PSA) less than 0.2 ng/ml.
- Patients unwilling to or unable to comply with the protocol
- Patients with impaired decision-making capacity
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, 02130-4817
Chong-Xian Pan, MD PhD, (857) 203-6189, chong-xian.pan@va.gov
Chong-Xian Pan, MD PhD
About this study
Official title: A Phase I Trial of Cancer-targeting Micelles for Non-myoinvasive Bladder Cancer
This clinical trial is to determine the safety and effectiveness of an investigational bladder cancer drug named "PLZ4-coated paclitaxel-loaded nanoscale micelle (PPM)." PPM is tiny particles that contain the chemotherapy drug paclitaxel. 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 instilled into the bladder cavity to treat bladder cancer that does not invade into the muscle layer of the bladder and that has failed the treatment of another drug Bacillus Calmette-Guérin (BCG). Up to 29 patients will be enrolled into the trial. The main goal of this trial is to determine the dose of PPM for future clinical trials, assess the toxicity and obtain preliminary data regarding its effectiveness.
Read the detailed description
The goal of this project is to conduct a Phase I clinical trial to determine the recommended Phase II dose (RP2D) of bladder cancer-targeting micelles loaded with a chemotherapeutic drug paclitaxel (PTX). The investigators previously developed a bladder cancer-specific targeting ligand named PLZ4, and a PLZ4-coated PTX-loaded nanoscale micelle (PPM) platform that can specifically deliver the drug load into bladder cancer cells both in vitro and in vivo. This proposed clinical trial is to conduct a first-in-human trial to use PPM for the treatment of non-myoinvasive bladder cancer (NMIBC). This primary objective of the proposed Phase I trial is to determine the recommended Phase II dose (RP2D) of PPM. The secondary objectives are to assess the toxicity, obtain preliminary efficacy information of PPM, and determine systemic absorption after intravesical instillation of PPM. Up to 29 patients with recurrent or refractory NMIBC after a standard first-line intravesical BCG treatment will be recruited. PPM will be given as intravesical instillation once weekly for six weeks. The toxicity will be assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The efficacy will be determined by urine cytology and cystoscopy after finishing treatment. Molecular correlative studies will be performed.
- Conditions
- Non-muscle-invasive Bladder Cancer
- Being tested
- PLZ4-coated paclitaxel-loaded micelles (PPM)
- Keywords
- non-muscle-invasive bladder cancer, BCG-refractory, paclitaxel, intravesical instillation
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PLZ4-coated paclitaxel-loaded micelles (PPM)Drug
PPM will be administrated weekly for 6 times through intravesical instillation into the bladder cavity
| Study group | Role | What they receive |
|---|---|---|
| Phase I dose-escalation and expansion cohort | Experimental | There are three doses at the dose escalation stage: Dose level I: paclitaxel (PTX) 25 Milligrams (mg) or 0.5 Milligrams (mg)/milliliter (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. Receives: Drug: PLZ4-coated paclitaxel-loaded micelles (PPM) |
What is being measured
The primary outcome is the main question the study is designed to answer.
adverse events
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be used to determine any adverse events and assess the grade. All toxicity as well as Grade 3 or higher adverse events will be analyzed.
Measured: up to 6 weeks after the last dose
Secondary outcomes (1)
complete response rate
urine cytology, cystoscopy.
Measured: 6 weeks after finishing the last dose of PPM
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2022
- Study start10 Oct 2022
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-muscle-invasive Bladder CancerStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a Phase I, single-group, dose-escalation trial
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University of California, Davis
- Responsible party
- Sponsor
- Investigators
- Chong-Xian Pan, MD PhD, Principal investigator, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05519241
- Sponsor's protocol ID
- ONCA-021-20S
- Other IDs
- VA Merit
- Status last verified
- Aug 2026
- First submitted
- 18 Aug 2022
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The published data is readily available after publications. Unpublished data will be available upon request. No individual participant data will be shared.
Publications
Pan CX, Mossanen M, Ellis JL, Ma AH, Yang C, Farrukh H, Jiao Y, Bhardwaj U, Lee JS, Lara PN, Hynes C, Lin TY, Li Y, Lerner L, Preston MA, Kibel A, Dall'Era M, Lam KS. Phase I first-in-human dose-escalation trial of a bladder cancer-specific nanoparticle in non-muscle-invasive bladder cancer. Nanomedicine (Lond). 2026 Jul;21(13):1865-1871. doi: 10.1080/17435889.2026.2693194. Epub 2026 Jul 8.
PubMed 42415671
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Cancer-targeting Micelles for Non-myoinvasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT05519241
- Acronym / sponsor ID
- ONCA-021-20S
- Conditions
- Non-muscle-invasive Bladder Cancer
- Keywords
- non-muscle-invasive bladder cancer, BCG-refractory, paclitaxel, intravesical instillation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University of California, Davis
- Study start
- 10 Oct 2022 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 29 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is to determine the safety and effectiveness of an investigational bladder cancer drug named "PLZ4-coated paclitaxel-loaded nanoscale micelle (PPM)." PPM is tiny particles that contain the chemotherapy drug paclitaxel. 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 instilled into the bladder cavity to treat bladder cancer that does not invade into the muscle layer of the bladder and that has failed the treatment of another drug Bacillus Calmette-Guérin (BCG). Up to 29 patients will be enrolled into the trial. The main goal of this trial is to determine the dose of PPM for future clinical trials, assess the toxicity and obtain preliminary data regarding its effectiveness.
Detailed description
The goal of this project is to conduct a Phase I clinical trial to determine the recommended Phase II dose (RP2D) of bladder cancer-targeting micelles loaded with a chemotherapeutic drug paclitaxel (PTX). The investigators previously developed a bladder cancer-specific targeting ligand named PLZ4, and a PLZ4-coated PTX-loaded nanoscale micelle (PPM) platform that can specifically deliver the drug load into bladder cancer cells both in vitro and in vivo. This proposed clinical trial is to conduct a first-in-human trial to use PPM for the treatment of non-myoinvasive bladder cancer (NMIBC). This primary objective of the proposed Phase I trial is to determine the recommended Phase II dose (RP2D) of PPM. The secondary objectives are to assess the toxicity, obtain preliminary efficacy information of PPM, and determine systemic absorption after intravesical instillation of PPM. Up to 29 patients with recurrent or refractory NMIBC after a standard first-line intravesical BCG treatment will be recruited. PPM will be given as intravesical instillation once weekly for six weeks. The toxicity will be assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The efficacy will be determined by urine cytology and cystoscopy after finishing treatment. Molecular correlative studies will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a Phase I, single-group, dose-escalation trial
| Arm | Type | Receives |
|---|---|---|
| Phase I dose-escalation and expansion cohort | Experimental | Drug: PLZ4-coated paclitaxel-loaded micelles (PPM)There are three doses at the dose escalation stage: Dose level I: paclitaxel (PTX) 25 Milligrams (mg) or 0.5 Milligrams (mg)/milliliter (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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Patients must meet all of the following criteria to be eligible for study entry.
- Histologically confirmed bladder carcinoma in situ (CIS) urothelial or urothelial carcinoma, with or without T1 cancer. Patients are eligible if the biopsy was done within 3 months of enrollment and a cystoscopy demonstrates no gross disease invasion into muscularis propria within 4 weeks of enrollment.
- Patient must have BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) or intolerance of treatment with BCG. Treatment of pembrolizumab is not an inclusion or exclusion criteria as intravesical taxane probably has comparable efficacy as intravenous pembrolizumab. BCG-unresponsive disease is defined as being at least one of the following:
- At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy
- At least five of six doses of an initial induction course plus at least two of six doses of a second induction course
Key exclusion criteria (19 listed)
- Patients who meet any of the following criteria will be excluded from study entry.
- Existence of cancer at the upper urinary tract
- Concurrent use of other investigational agents
- Evidence of regional and/or distant metastasis
- NYHA (New York Heart Association) Class III or IV heart failure, uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, or other clinical signs of severe cardiac dysfunction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PLZ4-coated paclitaxel-loaded micelles (PPM)PPM will be administrated weekly for 6 times through intravesical instillation into the bladder cavity | Drug | Phase I dose-escalation and expansion cohort |
Primary outcome
adverse events
Time frame: up to 6 weeks after the last dose
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be used to determine any adverse events and assess the grade. All toxicity as well as Grade 3 or higher adverse events will be analyzed.
1 secondary outcome
complete response rate
Time frame: 6 weeks after finishing the last dose of PPM
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
- Derived from this study: PubMed 42415671Pan CX, Mossanen M, Ellis JL, Ma AH, Yang C, Farrukh H, Jiao Y, Bhardwaj U, Lee JS, Lara PN, Hynes C, Lin TY, Li Y, Lerner L, Preston MA, Kibel A, Dall'Era M, Lam KS. Phase I first-in-human dose-escalation trial of a bladder cancer-specific nanoparticle in non-muscle-invasive bladder cancer. Nanomedicine (Lond). 2026 Jul;21(13):1865-1871. doi: 10.1080/17435889.2026.2693194. Epub 2026 Jul 8.
- Individual participant dataSharing planned: No. The published data is readily available after publications. Unpublished data will be available upon request. No individual participant data will be shared.
Related trials for Non-muscle-invasive Bladder Cancer
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Trial of Nadofaragene Firadenovec vs. Observation in Participants With Intermediate Risk Non-Muscle Invasive Bladder Cancer
Intermediate Risk Non-Muscle Invasive Bladder Cancer
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The Role of ERBT Plus Adjuvant Intravesical Induction and Maintenance Chemotherapy for Intermediate-Risk NMIBC
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RecruitingPhase 1
Inactivated UPEC-FimON for Non Muscle Invasive Bladder Cancer After BCG or Intravesical Chemotherapy Failure
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RecruitingPhase 3
A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer
Non-muscle Invasive Bladder Cancer With Carcinoma in Situ
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chong-Xian Pan, MD PhD principal investigator
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PLZ4-coated paclitaxel-loaded micelles (PPM) in people with Non-muscle-invasive Bladder Cancer, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chong-Xian Pan, MD PhD ((857) 203-6189, chong-xian.pan@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
adverse events (time frame: up to 6 weeks after the last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05519241, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.