RECRUITING

A Phase I Intravesical PPM Therapy for NMIBC

Conditions

Non-muscle-invasive Bladder Cancer BCG-refractory paclitaxel intravesical instillation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 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.

Official Title

A Phase I Trial of Cancer-targeting Micelles for Non-myoinvasive Bladder Cancer

Quick Facts

Study Start:2022-10-10

Study Completion:2026-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05519241

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * 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. * Age 18 years. * Performance status: ECOG performance status of 0, 1, or 2 (Appendix A) or Karnofsky performance status of 50 or higher (Appendix B). * 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 * Platelets 100,000/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.	* 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 (Appendix C), 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. * 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.

Inclusion Criteria

Exclusion Criteria

* 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
* 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.
* Age 18 years.
* Performance status: ECOG performance status of 0, 1, or 2 (Appendix A) or Karnofsky performance status of 50 or higher (Appendix B).
* 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
* Platelets 100,000/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.

* 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 (Appendix C), 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.
* 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.

Contacts and Locations

Study Contact

Chong-Xian Pan, MD PhD

CONTACT

(857) 203-6189

chong-xian.pan@va.gov

Lori Lerner, MD

CONTACT

(857) 364-6150

lori.lerner@va.gov

Principal Investigator

Chong-Xian Pan, MD PhD

PRINCIPAL_INVESTIGATOR

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

Study Locations (Sites)

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

Boston, Massachusetts, 02130-4817

United States

Collaborators and Investigators

Sponsor: VA Office of Research and Development

Chong-Xian Pan, MD PhD, PRINCIPAL_INVESTIGATOR, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-10-10

Study Completion Date2026-08-31

Study Record Updates

Study Start Date2022-10-10

Study Completion Date2026-08-31

Terms related to this study

Keywords Provided by Researchers

non-muscle-invasive bladder cancer
BCG-refractory
paclitaxel
intravesical instillation

Additional Relevant MeSH Terms

Non-muscle-invasive Bladder Cancer