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

  • STATUS
    Recruiting
  • End date
    Aug 31, 2026
  • participants needed
    29
  • sponsor
    VA Office of Research and Development
Updated on 27 October 2022

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. 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.

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.

Details
Condition Non-muscle-invasive Bladder Cancer
Treatment PLZ4-coated paclitaxel-loaded micelles (PPM)
Clinical Study IdentifierNCT05519241
SponsorVA Office of Research and Development
Last Modified on27 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
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
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
Exclusion Criteria
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 (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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note