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

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.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Other: sample collection; Other: sample collection; Other: Sample Collection

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Gtr Manchester
    • Manchester, Gtr Manchester, United Kingdom, M20 4BX
      • The Christie NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: sample collection; 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; Blood samples will be collected on days 1, 8, 15 and 22. They will be taken 30 minutes and 2 hours post Gemcitabine infusion.; Other: sample collection; Urine will be collected on days 1, 8, 15 and 22. They will be taken pre gemcitabine and 2 hours post Gemcitabine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Christie NHS Foundation Trust
• Collaborators: University of Oxford
• Investigators: Principal Investigator: Ananya Choudhury, Phd, The Christie NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2012
• Primary Completion (Actual): November 24, 2017
• Study Completion (Actual): November 24, 2017

Study Registration Dates

• First Submitted: April 7, 2011
• First Submitted That Met QC Criteria: April 26, 2011
• First Posted (Estimate): April 27, 2011

Study Record Updates

• Last Update Posted (Actual): August 13, 2021
• Last Update Submitted That Met QC Criteria: August 6, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Radiotherapy; Bladder Cancer; GemX Chemoradiotherapy
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: 10_DOG04_124