Neoadjuvant Chemotherapy Plus Nephroureterectomy for Locally Advanced Upper Tract Transitional Cell Cancer

Study Overview
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Brief Summary
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The purpose of this study is to test the effectiveness, safety and side effects of two chemotherapy drugs (gemcitabine and cisplatin) when combined with surgery after chemotherapy for patients with upper urinary tract cancer. The hypothesis is that undergoing chemotherapy prior to surgery will have a beneficial effect on prognosis and may improve overall survival as in patients with bladder cancer, and will allow better tolerance of chemotherapy than if it were given after surgery.

Detailed Description
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This study will look at improving overall survival of those undergoing nephroureterectomy for upper tract TCC (transitional cell carcinoma, comparing the pathological response of tumors treated with Neoadjuvant Chemotherapy (gemcitabine and cisplatin) before surgery. There have been reported studies of neoadjuvant chemotherapy in the treatment of upper tract TCC, there have been no studies to date that include the chemotherapy agents gemcitabine and cisplatin that are currently indicated in treating TCC of the bladder in the neoadjuvant and adjuvant setting. These agents have been proven to have a better overall safety profile and tolerability allowing more patients to complete their regimens. Secondarily, study will compare disease free overall survival among patients treated with neoadjuvant chemotherapy and surgery versus surgery alone. This study may elucidate the potential benefit of these agents when treating TCC of the upper tracts and may provide a survival advantage in this specific patient population as compared to a historical cohort.

Official Title
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Neoadjuvant Chemotherapy Plus Nephroureterectomy for Locally Advanced Upper Tract Transitional Cell Cancer

Conditions
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Transitional Cell Carcinoma

Intervention / Treatment
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* Drug: Gemcitabine and cisplatin
* Other: Retrospective comparison


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG performance status 0-2 Estimated GFR>60 High grade TCC on initial biopsy Clinical stage T1-T3, Nx, Mx based on the AJCC Classification system TCC confined to the ureter or renal pelvis Grade II neuropathy or less Exclusion Criteria: Any other malignancy over the previous five years with a risk of relapse that exceeds 30% History of previous cystectomy Evidence of metastatic disease History of pelvic irradiation or prior chemotherapy

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>A neoadjuvant chemotherapy (gemcitabine and cisplatin) regimen administered before surgery-nephroureterectomy for upper tract TCC | Drug: Gemcitabine and cisplatin<br>* Neoadjuvant chemotherapy (gemcitabine and cisplatin) administered before Nephroureterectomy. Chemotherapy regimen of three cycles of gemcitabine and cisplatin, dosed over a 3 month period Each cycle would consist of gemcitabine and cisplatin on day 1, with two other doses of gemcitabine on day 8 and day 15. Gemcitabine dosing would be 1,000 mg/m² and cisplatin would be dosed at 70 mg/m²<br>* Other names: Neoadjuvant Chemotherapy;|
| Other: 2<br>A retrospective cohort group (approximately 60 subjects) identified from an institutional cancer registry who have undergone a nephroureterectomy alone over the past five years | Other: Retrospective comparison<br>* 60 retrospective historical cohort group of subjects who have undergone a radical nephroureterectomy over the past five years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neoadjuvant chemotherapy (Gemcitabine and Cisplatin) Regime (3 cycles) before Nephroureterectomy |  | 5 years: follow ups 1st year/every 4 mths, 2nd & 3rd year to every 6 months, 4th & 5th yr-annually for patients who remain disease free | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival compared to institutional historical cohort of subjects who have undergone a nephroureterectomy alone. |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Upper GU Tract Transitional Cell Carinoma, Nephroureterectomy, Chemotherapy, Gemcitabine, Cisplatin