Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Contact information



Primary contact

Dr Tom Geldart


Contact details

Department of Oncology and Haematology
Royal Bournemouth Hospital
Castle Lane East
United Kingdom
+44 (0)1202 726088

Additional identifiers

EudraCT number

2007-007591-42 number


Protocol/serial number

SPON 416-07; C9325/A9347

Study information

Scientific title

A phase II single-arm trial to evaluate cisplatin and gemcitabine chemotherapy in combination with sunitinib for first-line treatment of patients with advanced transitional carcinoma of the urothelium



Study hypothesis

The prognosis for patients with advanced urothelial cancer (predominantly bladder) is poor and approximately 4,700 patients in the United Kingdom (UK) die each year from the disease. Approximately 50% of patients who are fit enough to undergo cisplatin-based chemotherapy will respond to treatment. Median progression-free survival for such patients is approximately 8 months and median overall survival 14 months. Despite a recent increase in our understanding of the molecular basis of bladder cancer, there have been few clinical studies using molecularly-targeted compounds in advanced urothelial cancer.

Sunitinib (Sutent®) is an oral drug that slows down tumour growth and prevents the formation of new blood vessels associated with cancer growth. Clinical trial data has recently demonstrated sunitinib to be highly active in some cancers, including advanced kidney cancer and rare types of stomach cancer. Early phase clinical trial data confirms that sunitinib is active in urothelial cancer. Additional data also demonstrates that sunitinib can be safely combined with standard cisplatin based chemotherapy. This trial will assess whether the addition of sunitinib to standard cisplatin/gemcitibine cancer chemotherapy improves outcome for patients with advanced urothelial disease.

On 24/02/2011 the overall trial end date was changed from 01/12/2010 to 01/10/2011.

Ethics approval

West of Scotland Research Ethics Committee on 03/12/2008 (ref: 08/S0703/123).
Each participating centre will be approved through a Regional Ethics Committee (REC) prior to patient recruitment.

Study design

A late phase II single-arm non-randomised open-label multicentre trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Locally advanced and/or metastatic transitional cell carcinoma of the urothelium


Patients will be recruited over approximately 18 months. All patients will receive a maximum of six, 21 day cycles of cisplatin and gemcitabine chemotherapy in combination with sunitinib. Each treatment cycle will consist of:
1. Cisplatin 70 mg/m^2 intravenously on day one
2. Gemcitabine 1000 mg/m^2 intravenously on days one and eight
3. Sunitinib 37.5 mg once daily orally on days 2 - 15

Dose modifications or discontinuation of treatment due to toxicity will be implemented according to specific criteria. Assessments will be performed at baseline, at specified times during trial treatment, and at 6 and 12 months from date of enrolment, as per timelines specified in the trial protocol, and including:
1. Diagnostic biopsy and cystoscopy (where appropriate)
2. Cross-sectional imaging (chest, abdomen and pelvis)
3. Physical exam (including height, weight and blood pressure)
4. WHO performance status
5. Haematology
6. Serum biochemistry
7. Thyroid function test
8. Isotopic GFR
9. Isotope bone scintigram (if clinically relevant)
10. Electrocardiogram
11. Plain film chest x-ray
12. Toxicity and late toxicity
13. Pregnancy test (females of childbearing potential)

Additional blood samples will be requested at baseline, and at 6 and 12 months after date of enrolment, for patients participating in an optional translational/pharmacodynamic sub-study. Permission will also be sought to analyse sections of previous histological specimens. These additional samples will be analysed as part of a translational sub-study that will be submitted for separate funding and addressed by separate questions on patient consent form.

Disease response/progression and performance status will be assessed by cross-sectional imaging at baseline, after cycle three of treatment (week 9) and 6 and 12 months after date of enrolment.

If results confirm sufficient activity of the three-drug chemotherapy, the combination treatment will be taken forward into a randomised phase III setting.

Intervention type



Phase II

Drug names

Sunitinib (Sutent®), cisplatin, gemcitabine

Primary outcome measure

Activity assessed as progression-free survival at 6 months

Secondary outcome measures

1. Toxicity, during and after treatment: measured at baseline (less than or equal to one week before treatment) and every 21 days whilst on treatment to coincide with the beginning of each new treatment cycle. Late toxicity will be measured at the end of treatment, and at 6 and 12 months from date of enrolment. Serious adverse events (SAEs) will be collected in real time.
2. Tolerability and feasibility of use: determined as the number of patients requiring dose delays or reduction and/or treatment withdrawal and will be determined after all patients have completed treatment
3. Overall survival: calculated at the end of the study duration (2.5 years) based on the time of enrolment to date of death or date censored (date last known to be alive)
4. Progression-free survival (time-to-event): calculated as the time from enrolment to any disease progression and/or death. Those progression-free and alive will be censored at time last seen.
5. Objective response rate: determined relative to baseline prior to treatment cycle four (week nine) and at 6 and 12 months from date of completion of treatment

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Aged greater than or equal to 18 years, either sex
2. Histologically confirmed transitional cell carcinoma (pure or mixed histology) of urothelium (upper or lower urinary tract)
3. Radiologically measurable locally advanced and/or metastatic disease (T4b Nany Many, Tany N2-3 Many or Tany Nany M1) not amenable to curative treatment with surgery or radiotherapy
4. Estimated life expectancy greater than three months
5. World Health Organization (WHO) performance status 0 - 2
6. Fit to receive cisplatin-containing combination chemotherapy
7. No prior systemic therapy for locally advanced or metastatic disease - patients who have received prior neoadjuvant or adjuvant chemotherapy for urothelial cancer (up to four cycles), completed at least six months prior to first documented disease progression will remain eligible
8. No prior radiotherapy within one month prior to registration or involving more than 30% of total bone marrow volume
9. No investigational drug within one month prior to registration
10. Adequate renal function (glomerular filtration rate [GFR] greater than 60 ml/min, uncorrected for surface area and measured by isotopic means
11. Adequate bone marrow function (absolute neutrophil count greater than or equal to 1.5 x 10^9/l; platelets greater than or equal to 100 x 10^9/l at baseline)
12. Adequate liver function (bilirubin less than or equal to 1.5 x upper limit of normal [ULN]; alanine aminotransferase [ALT] and alkaline phosphatase [ALP] less than or equal to 2.5 ULN at baseline)
13. Prothrombin time (PT) or International normalised ratio (INR) less than or equal to 1.5 x ULN
14. Written informed consent

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Patients with transitional cell cancer in whom subsequent radical treatment is being considered with a view to possible cure
2. Previous malignancy other than non-melanoma skin cancer, cervical carcinoma in situ or incidental localised prostate cancer
3. Previously-identified central nervous system (CNS) metastases - routine baseline computed tomography (CT) scanning of the head is not a requirement for trial entry and should only be performed if clinically indicated
4. Women who are pregnant or breast feeding. Woman of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of trial therapy.
5. Men and women not prepared to practice method(s) of birth control of established efficacy
6. Known infection with human immunodeficiency virus (HIV) or chronic hepatitis B or C
7. Uncontrolled hypertension
8. Symptomatic coronary artery disease, myocardial infarction within the last six months, congestive cardiac failure greater than New York Heart Association [NYHA] class II, uncontrolled or symptomatic cardiac arrhythmia
9. Clinically significant bacterial or fungal infection
10. Concurrent anticoagulant therapy with warfarin or un-fractionated heparin - patients requiring anti-coagulation may be entered after successful conversion to low molecular weight heparin (LMWH)
11. Concomitant medication which have adverse interactions with sunitinib

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Royal Bournemouth Hospital
United Kingdom

Sponsor information


Cardiff University (UK)

Sponsor details

Research and Commercial Division (RACD)
7th Floor
30 - 36 Newport Road
United Kingdom

Sponsor type




Funder type


Funder name

Cancer Research UK (CRUK) (UK) (ref: C9325/A9347) - grant funded by the Feasibility Study Committee (FSC)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Pfizer (UK) - provided sunitinib and its distribution costs free-of-charge (subject to contract)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

The Wales Cancer Trials Unit (WCTU) is core funded by CRUK and WCTU core resources will be used to support this trial.

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Available on request

Basic results (scientific)

Publication list

2015 results in:

Publication citations

Additional files

Editorial Notes

05/08/2019: The overall trial end date has been changed from 08/07/2013 to 18/07/2013. 24/07/2019: The overall trial end date has been changed from 09/10/2014 to 08/07/2013. 08/02/2016: The overall trial start and end dates have been updated from 01/07/2008 - 01/10/2011 to 01/04/2008 - 09/10/2014 and the recruitment start and end dates have been updated from 01/07/2008 - 01/10/2011 to 20/07/2009 - 01/02/2013.