Neoadjuvant Rapamycin in Patients Undergoing Radical Cystectomy

Study Overview
=================
Brief Summary
-----------------
This study aims to evaluate the effects of rapamycin directly on bladder tumors and the effects of rapamycin on the immune system of patients with bladder cancer.

Detailed Description
-----------------
This is a presurgical clinical trial which aims to understand the biologic activity of TORC1 inhibition and safety in patients with bladder cancer. In this presurgical setting, paired PMBCs and tumor tissue is evaluated before and after exposure to rapamycin to address target specificity, drug delivery, physiologic effects on tumor growth and apoptosis, and correlation of biomarkers with clinical activity.

Official Title
-----------------
An Immunopharmacodynamic Phase 0/I Study of Rapamycin in Patients Undergoing Radical Cystectomy for Bladder Cancer

Conditions
-----------------
Invasive Bladder Cancer Stage II

Intervention / Treatment
-----------------
* Drug: Rapamycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have invasive (≥T1) bladder cancer Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 In their treating physician's opinion is a good candidate for radical cystectomy In their treating physician's opinion does not need neoadjuvant chemotherapy prior to cystectomy Be able to give informed consent Be age 18 or older Have adequate marrow function (defined as granulocytes greater than 1,500 cells/mm3 hemoglobin >9.5 gm/dl or platelets more than 100,000 cells/mm3). Have adequate end-organ function (GFR >30, bilirubin <1.5, SGOT < 3x ULN) Have a life expectancy > one year Not have a prior history of non-bladder cancer unless the cancer is clinically stable and not requiring active treatment Not have received chemotherapy or radiotherapy in the prior 30 days Exclusion Criteria: Immunosuppressed state (e.g. HIV, use of chronic steroids) Fixed disease (clinical T4) Active, uncontrolled infections Hepatic impairment (SGOT >3x ULN) Unhealed wounds Patients at risk of pregnancy who are unwilling or unable to take effective contraception before rapamycin therapy, during therapy, and for 12 weeks after discontinuation of therapy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycin<br>Rapamycin 3mg orally daily x 4weeks prior to radical cystectomy | Drug: Rapamycin<br> <br> * Other names: Sirolimus, Rapamune;|
| No Intervention: Control<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue pharmacodynamic (PD) response to TORC1 inhibition | PD response defined by significant phospho rpS6 Kinase 1 (S6K1) inhibition (comparing post-treatment to baseline). | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bladder, Cancer, Cystectomy, Rapamycin