Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Ms Carey Hendron
ORCID ID
Contact details
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 121 414 3344
c.hendron@bham.ac.uk
Additional identifiers
EudraCT number
2009-014805-15
ClinicalTrials.gov number
Protocol/serial number
7949
Study information
Scientific title
Phase I/II feasibility study of cetuximab with 5-fluorouracil (5FU) and mitomycin C or cisplatin with concurrent radiotherapy in muscle invasive bladder cancer
Acronym
TUXEDO
Study hypothesis
This is a Phase I combination study, followed by an early phase II, single-arm, multicentre, open-label study.
The primary objective of the phase I study is to determine the feasibility and toxicity profile of cetuximab with 5FU and mitomycin C, and in addition to determine the optimal dose of cisplatin in combination with cetuximab. Feasibility will be based on assessment of using the proposed drugs in combination with radical radiotherapy.
The primary objective of the phase II study is to assess preliminary evidence of the efficacy of the treatment selected from phase I, by determining whether a combination of radiotherapy with cetuximab, and chemotherapy, improves cystoscopic local control of advanced bladder cancer at three months after treatment.
Ethics approval
11/LO/1313
Study design
Non-randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Bladder Cancer; Disease: Bladder (advanced)
Intervention
1. FU: In cohort I, patients receive 5FU in weeks 1 and 4 as a continuous infusion for 5 days (total of 10 days) concurrently with radiotherapy 2. Cetuximab, Loading dose given in week before start of RT, then given on day 1 of each week of RT (weeks 1 - 7)
3. Cisplatin: Patients in cohorts II and III of phase I receive cisplatin on the first day of each week of radiotherapy (weeks 1 - 7)
4. Mitomycin C: In cohort I, patients receive mitomycin C on day 1 only of week 1 of radiotherapy
5. Radical Radiotherapy: All patients in the study receive 64Gy in 32 fractions (given over 5 days in weeks 1 - 7)
Follow Up Length: 18 month(s); Study Entry : Registration only
Intervention type
Drug
Phase
Phase I/II
Drug names
Mitomycin C, 5FU, cetuximab, cisplatin
Primary outcome measures
Feasibility and toxicity; Timepoint(s): Phase I outcome
Secondary outcome measures
Cystoscopic local control at three months post-treatment; Timepoint(s): Primary outcome in Phase II
Overall trial start date
07/11/2011
Overall trial end date
29/11/2013
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged 18 or over
2. Histologically proven invasive bladder carcinoma [adenocarcinoma, transitional cell carcinoma (TCC) or squamous cell carcinoma (SCC)]
3. Localised muscle invasive carcinoma either surgically or by imaging (T2-T4a N0 M0)
4. World Health Organisation (WHO) performance status grade 0 to 1
5. Adequate haematological function (haemoglobin > 10g/dl; white blood cells (WBC) > 3.0x109/L; absolute neutrophils count (ANC) > 1.5x109/L; platelet count > 100,000/mm3)
6. Adequate hepatic function {billirubin < 1.5 upper limit fo normal (ULN), Alkaline phosphatase (ALP) < 2xULN, [aspartate aminotransferase (AST)/alanine aminotransferase (ALT)] < 3.0xULN}
7. Glomerular filtration rate (GFR) > 40 ml/min [by ethylenediamine tetraacetic acid (EDTA) clearance, 24h urine collection, or Cockcroft-Gault]
8. Available for long-term follow-up
9. Able to receive a radical course of radiotherapy
10. Patients written informed consent
11. Have received 3-4 cycles of neo-adjuvant chemotherapy (preferably Gemcitabine/Cisplatin) with a positive response (confirmed by cystoscopy & radiological response) with pre neo-adjuvant imaging computerised tomography (CT) scan or magnetic resonance imaging (MRI) of abdomen and pelvis.; Target Gender: Male & Female ; Lower Age Limit 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 60; UK Sample Size: 60
Participant exclusion criteria
1. Uncontrolled systemic disease which would preclude the patient from participating in the study including severe or uncontrolled cardiovascular disease (congestive heart failure New York Heart Association (NYHA) III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias
2. Pregnant or breast feeding
3. Concomitant or previous malignancy which is likely to interfere with protocol treatment
4. Inflammatory bowel disease
5. Previous pelvic radiotherapy
6. Bilateral hip replacements compromising accurate radiotherapy planning
7. 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
8. Male and female patients (of childbearing age) not using adequate contraception
9. Significant decrease in GFR during previous chemotherapy treatments
10. Widespread carcinoma in situ (CIS), or CIS remote from the muscle invasive tumour
11. Simultaneous upper tract, urethral or prostatic transitional cell carcinoma
12. Untreated hydronephrosis
13. Participation in another trial within the previous 30 days [except for observational studies, e.g. Bladder Cancer Prognosis Programme (BCPP)]
Recruitment start date
07/11/2011
Recruitment end date
29/11/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom
Sponsor information
Organisation
University of Birmingham
Sponsor details
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Clinical Trials Awards and Advisory Committee (CTAAC) (UK) Grant Codes: C547/A10900
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary