Locally advanced and/or metastatic transitional cell carcinoma of the urothelium Cancer Malignant neoplasm of genital organs
Conditions
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 treatme
Sponsors
Cardiff University (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Activity assessed as progression-free survival at 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
England, United Kingdom
Outcome results
None listed