Phase I & II Trial of Intravesicular Abraxane for Treatment-refractory Bladder Cancer

Study Overview
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Brief Summary
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The intravesical treatment of bladder cancer with Abraxane is more desirable than other taxanes due to its ability to be diluted in water and not lipid-based solutions allowing it greater access to sites in the bladder. Thus, we are interested in investigating Abraxane's safety, toxicity, and efficacy profile for the treatment of recurrent transitional cell cancer of the urinary bladder in a combined phase I & II trial. The phase I trial is designed as a dose-escalation study with cohorts of threes that will enroll a maximum of 18 patients. Dose increases will occur in groups of three patients, with each successive group receiving an increased concentration of Abraxane intravesically. No dose increase will occur until each member of the previous cohort has undergone the first instillation of the medication without experiencing a dose-limiting toxicity (DLT). Any patient who experiences a DLT will be removed from the trial and treated appropriately. If one patient in the cohort experiences a DLT an additional three patients will be enrolled and treated at that dose-level. If none of the additional three patients experience a DLT, the next group of patients will be started on the next higher dose level. If at any dose level, two or more patients experience a DLT the previous dose level will be considered as the maximum tolerated dose (MTD). An additional three patients (for a total of six patients) will then be treated at the MTD. If less than two patients experience a DLT this dose level will be established as the MTD. The phase II aspect is designed in a Simon II stage format in which to satisfy our study powering, the first stage there will be 10 patients enrolled. If there are 2 or more successful treatments in that group (negative urine cytology and bladder biopsy after 6 months), then the first stage will pass the rejection rule, and up to another 19 patients will be enrolled. If at any point in the study, there have been a total of 6 or more successes, then the phase II aspect will be considered a successful trial and the study will be completed at that point.

Official Title
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A Combined Phase I & II Trial of Intravesicular Abraxane, a Nanoparticle Albumin-bound Paclitaxel, for Treatment-refractory Transitional Cell Carcinoma of the Urinary Bladder

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Paclitaxel, nanoparticle albumin-bound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of transitional cell carcinoma (TCC) of the urinary bladder confirmed at the study institution. The patient must have demonstrated superficial recurrent bladder cancer refractory to standard intravesical therapy. This will include stage Ta, T1, Tis and exclude all patients with muscle invasion (T2). All patients with stage Ta will require documentation of high-grade histology. All grossly visible disease must be fully resected and pathologic stage will be confirmed at the institution where the patient is enrolled. Patients must exhibit disease recurrence after receiving some form of standard intravesical therapy, including BCG, mitomycin, interferon or any combination thereof. Age > 18 and must be able to read, understand and sign informed consent Performance Status: ECOG 0,1 (See Appendix II ) Peripheral neuropathy: must be < grade 1 Hematologic-Inclusion within 2 weeks of start of treatment Absolute neutrophil count > 1,500/mm3 Hemoglobin >9.0 g/dl Platelet count > 100,000/mm3 Hepatic-Inclusion within 2 weeks of entry Total Bilirubin must be within normal limits. Adequate renal function with serum creatinine ≤ 2.0 mg/dL Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution, Alkaline phosphatase ≤ 2.5 x ULN for the institution, unless bone metastasis is present in the absence of liver metastasis Women of childbearing potential must have a negative pregnancy test. All patients of childbearing potential must be willing to consent to using effective contraception, i.e., IUD, Birth control pills, Depo-Provera, and condoms while on treatment and for 3 months after their participation in the study ends. No intravesical therapy within 6 weeks of study entry No prior radiation to the pelvis Exclusion Criteria: Prior systemic docetaxel or paclitaxel therapy. Any other malignancy diagnosed within 2 years of study entry (except basal or squamous cell skin cancers or non-invasive cancer of the cervix) is excluded. Concurrent treatment with any chemotherapeutic agent. Women who are pregnant or lactating. History of vesicoureteral reflux or an indwelling urinary stent. Participation in any other research protocol involving administration of an investigational agent within 3 months prior to study entry aside from the phase I segment of this study. History of neuropathy of any cause

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abraxane administration<br>Patients will restrict their fluid intakes the morning of treatments and will have emptied their bladders at each of their visits and have up to 100ml of Abraxane solution administered to their bladder via urinary catheter once weekly for six weeks. | Drug: Paclitaxel, nanoparticle albumin-bound<br>* Intravesically administered, dose escalation, 6 weekly instillations<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety, toxicity and efficacy profiles of intravesically administered Abraxane at the Maximum Tolerated Dose. |  | 6 weeks, 4 months, 6 months | 
| To evaluate the utility (potential for clinical efficacy) of Abraxane in the treatment of refractory superficial TCC as measured by response rate (defined as negative cytology and bladder biopsy). |  | 6 weeks, 4 months, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To further evaluate the safety and toxicity profile of intravesically administered Abraxane therapy. |  | 6 weeks, 4 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder Cancer, Chemotherapy, Bladder Neoplasms