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| [ Print-friendly version ] |
| Sunitinib in advanced urothelial cancer in combination with standard cisplatin/gemcitabine chemotherapy treatment |
| ISRCTN | ISRCTN54607216 |
| ClinicalTrials.gov identifier | |
| Public title | Sunitinib in advanced urothelial cancer in combination with standard cisplatin/gemcitabine chemotherapy treatment |
| 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 |
| Acronym | SUCCINCT |
| Serial number at source | SPON 416-07; C9325/A9347; Eudract 2007-007591-42 |
| 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. |
| Ethics approval | Protocol approval will be sought from a Multicentre Research Ethics Committee (MREC). 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 |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Locally advanced and/or metastatic transitional cell carcinoma of the urothelium |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 01/07/2008 |
| Anticipated end date | 01/12/2010 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 63 |
| Interventions |
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 child bearing 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. |
| Primary outcome measure(s) | Activity assessed as progression-free survival at 6 months. |
| Secondary outcome measure(s) |
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 |
| Sources of funding |
1. Cancer Research UK (CRUK) (UK) (ref: C9325/A9347) - grant funded by the Feasibility Study Committee (FSC)
2. Pfizer (UK) - provided sunitinib and its distribution costs free-of-charge (subject to contract) The Wales Cancer Trials Unit (WCTU) is core funded by CRUK and WCTU core resources will be used to support this trial. |
| Trial website | |
| Publications | |
| Contact name | Dr Tom Geldart |
| Address |
Department of Oncology and Haematology
Royal Bournemouth Hospital Castle Lane East |
| City/town | Bournemouth |
| Zip/Postcode | BH7 7DW |
| Country | United Kingdom |
| Tel | +44 (0)1202 726088 |
| Fax | +44 (0)1202 704134 |
| tom.geldart@rbch.nhs.uk | |
| Sponsor | Cardiff University (UK) |
| Address |
Research and Commercial Division (RACD)
7th Floor 30 - 36 Newport Road |
| City/town | Cardiff |
| Zip/Postcode | CF24 ODE |
| Country | United Kingdom |
| Sponsor website: | http://www.cf.ac.uk/racdv/index.html |
| Date applied | 11/03/2008 |
| Last edited | 25/04/2008 |
| Date ISRCTN assigned | 25/04/2008 |
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