Neoadjuvant ABI-007, Carboplatin and Gemcitabine in Locally Advanced Bladder Cancer

Study Overview
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Brief Summary
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Study participants will have been diagnosed with bladder cancer that has invaded the muscle wall of the bladder. Surgery is used to remove cancer when it is in the muscle of the bladder. Unfortunately, approximately 50% of people may have their cancer return in another location. For this reason, researchers are focusing on new chemotherapy regimens to be given before surgery (to remove the bladder) that may decrease the likelihood of cancer spreading. Paclitaxel, carboplatin and gemcitabine are chemotherapy drugs known to destroy bladder cancer cells. ABI-007 (brand name Abraxane™) is a form of the chemotherapy drug called paclitaxel. Standard paclitaxel is formulated with ethanol and a substance called Cremophor EL (polyoxyethylated castor oil). However, these additives are felt to contribute to the side effects (possibly severe) associated with paclitaxel. ABI-007 does not contain these additives and may deliver more drug to tumor cells. ABI-007 is approved by the United States Food and Drug Administration (FDA) in the treatment of metastatic (advanced) breast cancer, and is being evaluated in other cancers in research studies. This study will evaluate the safety and efficacy of the combination of ABI-007, carboplatin and gemcitabine in the treatment of bladder cancer prior to surgery to remove the bladder.

Official Title
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A Phase Two Trial of Neoadjuvant ABI-007, Carboplatin and Gemcitabine in Patients With Locally Advanced Carcinoma of the Bladder

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: ABI-007
* Drug: Carboplatin
* Drug: Gemcitabine
* Procedure: Radical Cystectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven locally advanced (T2-4,N0,M0 or Tany,N1-3,M0) urothelial carcinoma of the bladder and be candidates for cystectomy following chemotherapy. Tumor specimens must be available for assay of molecular markers (correlative research). Performance status of 0, 1 or 2 by Eastern Cooperative Oncology Group (ECOG) criteria. Serum creatinine <2.0 mg/dl and/or creatinine clearance >40 ml/min. Granulocyte count > 1,500/mm3, platelet > 100,000/mm3, and hemoglobin > 9.0 g/dl. Adequate liver functions: AST and ALT < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, and bilirubin < 1.5 mg/dl. Pre-existing peripheral neuropathy > grade 2 Recovered from any effects of surgery. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Women with reproductive potential must have a negative pregnancy test. Exclusion Criteria: Prior systemic or intra-arterial chemotherapy and rior radiotherapy. (intravesical chemotherapy allowed.) Pre-existing peripheral neuropathy > grade 2 Prior malignancy [except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for 2 years] Unresolved bacterial infection requiring active treatment with antibiotics. (Treatment may begin at the conclusion of antibiotic therapy.) Pregnant or lactating women may not participate.

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: Neoadjuvant ABI-007, Carboplatin, and Gemcitabine<br>Neoadjuvant ABI-007 (260 mg/m^2) on day 1, Carboplatin (Target AUC [Area under the curve] =5) on day 1, and Gemcitabine (800 mg^m2) on days 1 and 8, every 21 days. | Drug: ABI-007<br>* ABI-007 will be administered at a dose of 260 mg/m2 over a 30 min IV infusion on day 1 of each 21 day cycle.<br>Drug: Carboplatin<br>* Carboplatin will be administered at a dose of TARGET AUC=5 over a 15 min IV infusion of day 1 of each 21 day cycle.<br>Drug: Gemcitabine<br>* Gemcitabine will be administered at a dose of 800 mg/m2 over a 30 min IV infusion on days 1 and 8 of each 21 day cycle.<br>Procedure: Radical Cystectomy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment | The rate of pathologic complete response (pT0) following three 21 day cycles of neoadjuvant ABI-007, carboplatin and gemcitabine was determined. | 63 days (post 3 cycles) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced urothelial carcinoma of the bladder