Phase I/II feasibility study of cetuximab with 5-fluorouracil (5FU) and mitomycin C or cisplatin with concurrent radiotherapy in muscle invasive bladder cancer
| ISRCTN | ISRCTN80733590 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN80733590 |
| EudraCT/CTIS number | 2009-014805-15 |
| Secondary identifying numbers | 7949 |
- Submission date
- 17/08/2011
- Registration date
- 17/08/2011
- Last edited
- 11/01/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Mrs Baljit Kaur
Scientific
Scientific
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 121 414 3793 |
|---|---|
| b.kaur@bham.ac.uk |
Study information
| Study design | Non-randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| Study acronym | TUXEDO |
| Study objectives | 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(s) | 11/LO/1313 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | Mitomycin C, 5FU, cetuximab, cisplatin |
| Primary outcome measure | 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 study start date | 07/11/2011 |
| Completion date | 29/11/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 60; UK Sample Size: 60 |
| Total final enrolment | 33 |
| Key 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 |
| Key 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)] |
| Date of first enrolment | 07/11/2011 |
| Date of final enrolment | 29/11/2013 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom
B15 2TT
United Kingdom
Sponsor information
University of Birmingham
University/education
University/education
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Website | http://www.birmingham.ac.uk |
|---|---|
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
Clinical Trials Awards and Advisory Committee (CTAAC) (UK) Grant Codes: C547/A10900
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not added at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | 20/05/2017 | 14/04/2022 | No | No | |
| Abstract results | 20/02/2020 | 14/04/2022 | No | No | |
| Other publications | Results of sub-study investigating whether urinary DNA analysis can be used to investigate whether treatment response is associated with tumor mutations | 07/09/2021 | 14/04/2022 | Yes | No |
| Results article | 31/07/2022 | 02/08/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
11/01/2023: Cancer Research UK plain English summary link added to plain English summary field.
02/08/2022: Publication reference added.
14/04/2022: The following changes have been made:
1. Publication references added.
2. The final enrolment number has been added from the reference.
09/09/2019: The contact details were updated.
30/04/2018: Conference proceedings added to publication and dissemination plan.
09/03/2016: No publications found, verifying study status with principal investigator.
