Non-muscle-invasive Bladder Cancer
Conditions
Keywords
non-muscle-invasive bladder cancer, BCG-refractory, paclitaxel, intravesical instillation
Brief 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 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.
Interventions
DRUGPLZ4-coated paclitaxel-loaded micelles (PPM)
PPM will be administrated weekly for 6 times through intravesical instillation into the bladder cavity
Sponsors
VA Office of Research and Development
University of California, Davis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a Phase I, single-group, dose-escalation trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| adverse events | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| complete response rate | 6 weeks after finishing the last dose of PPM | urine cytology, cystoscopy. |
Countries
United States
Contacts
CONTACTChong-Xian Pan, MD PhD
CONTACTLori Lerner, MD
PRINCIPAL_INVESTIGATORChong-Xian Pan, MD PhD
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Outcome results
None listed