Measurement of Gemcitabine Metabolites in Blood and Urine as Predictors of Response to GemX Bladder Radiotherapy

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that plasma, peripheral blood mononuclear cell and urine levels of Gemcitabine and its metabolites, 30 mins or 2 hours post infusion, predict response to GemX chemoradiation at first check cystoscopy, 3 months from the end of radiotherapy.

Official Title
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Measurement of Gemcitabine Metabolites in Blood and Urine as Predictors of Response to GemX Bladder Radiotherapy

Conditions
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Bladder Cancer

Intervention / Treatment
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* Other: sample collection
* Other: sample collection
* Other: Sample Collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed diagnosis of muscle-invasive transitional cell carcinoma. suitable for treatment with radical concurrent chemoradiotherapy with GemX. Standard radiological assessments with CT or MR for staging. ECOG performance status 0-2 Adequate pre-treatment haematological and biochemical parameters Age greater than or equal to 18 years No significant co-morbidity thereby excluding patient from having radical treatment. No previous treatment for diagnosis of muscle-invasive bladder cancer or other pelvic radiotherapy. Women of child bearing age MUST have a negative pregnancy test prior to study entry and be using an adequate contraception method, which must be continued for 3 months after the study, unless child bearing potential has been terminated by surgery/radical radiotherapy Patients must have given written informed consent Exclusion Criteria: Patients with a known history of anaphylactic reaction to any other drug. Patients must not have a history of other malignant diseases other than adequately treated non-melanotic skin cancer or in-situ carcinoma of the uterine cervix Any evidence of severe or uncontrolled systemic diseases which, in the view of the investigator, makes it undesirable for the patient to participate in the trial. Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator makes it undesirable for the patient to participate in the trial Any other serious uncontrolled medical conditions Clinical evidence of metastatic disease to brain Any pregnant or lactating woman Any patient with a medical or psychiatric condition that impairs their ability to give informed consent

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: sample collection<br>This is a single arm study. Patients will be seen on day 1, 8, 15 and 22 and will have the following samples collected: Pre gemcitabine urine sample Blood sample 30 minutes post Gemcitabine infusion Urine and blood sample 2 hours post Gemcitabine infusion | Other: sample collection<br>* Blood samples will be collected on days 1, 8, 15 and 22. They will be taken 30 minutes and 2 hours post Gemcitabine infusion.<br>Other: sample collection<br>* Urine will be collected on days 1, 8, 15 and 22. They will be taken pre gemcitabine and 2 hours post Gemcitabine<br>Other: Sample Collection<br>* Quality of Life (QOL) questionnaires given to the patient at each visit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Does response at Cystoscopy correlate with results of sample analysis | To test the hypothesis that plasma, peripheral blood mononuclear cell and urine levels of gemcitabine and its metabolites, 30 mins or 2 hrs post-infusion, predict response to GemX chemoradiation at first check cystoscopy, 3 months from the end of radiotherapy. Gemcitabine will be measured in plasma by HPLC-MS using a published validated method. We have developed an assay for intracellular gemcitabine triphosphate which should determine levels in PBMCs from 10 - 15 ml blood. Response at Cystoscopy is measured as either complete response, superficial disease or muscle-invasive disease. | 3 months following the end of GemX chemoradiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cause-specific and overall survival rates |  | 3 years | 
| acute and late toxicities as assessed by RTOG and LENT SOM scales | Toxicity is measured using LENT-SOMA (patient-reported) and CTCAE v4.0 (clinical assessment) during treatment and at follow up. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy, GemX Chemoradiotherapy, Bladder Cancer