E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced transitional cell carcinoma of the urothelium. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038517 |
E.1.2 | Term | Renal pelvis cancer NOS |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046375 |
E.1.2 | Term | Ureter cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this trial is to assess whether the addition of sunitinib to standard cisplatin / gemcitabine (CG) cancer chemotherapy improves outcome for participants with advanced cancer of the urinary system (urothelial cancer). The primary objective is to assess the activity, safety and feasibility of using the 3−drug combination (SCG) in patients with advanced transitional cell carcinoma of the urothelium. The primary outcome measure is progression−free survival (PFS) at 6 months from date of enrolment. This is the proportion of participants who are alive at 6 months without disease progression, according to RECIST (Response Evaluation Criteria In Solid Tumours). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to determine: • Toxicity, during and after treatment • Tolerability (side effects) and feasibility of use (number of participants requiring dose delays or reduction and / or treatment withdrawal) • Overall survival, defined by time from enrolment to death by any cause. Those still alive will be censored at the time last seen. • Progression−free survival (time−to−event). Time from registration to any disease progression (based on RECIST) and/or death. Those progression−free and alive will be censored at the time last seen. • Objective (radiological) response rate based on RECIST |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Participants will be asked to participate in an optional sub-study of the main SUCCINCT trial (see full title provided in Section A.3 of this form) and detailed in Setion 12.0 Ancillary Studies of the trial protocol supplied with this application (Version Number 3.0, 4th August 2010). All SUCCINCT participants will be asked to consider the provision of additional blood samples before and after the SUCCINCT trial treatment, and for permission to analyse previous tumour tissue specimens (e.g. from prior TURBT and/or cystectomy / nephro-ureterectomy). The objective is to analyse these samples to gain a better understanding of the 3-drug SCG treatment in urothelial cancer. |
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E.3 | Principal inclusion criteria |
1. Age greater than or equal to 16 years 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 not amenable to curative treatment with surgery or radiotherapy: (a) T4b (bladder) / T4 (renal pelvis / ureter) Nany Many, (b) Tany N2−3 Many, (c) Tany Nany M1 4. Estimated life expectancy greater than 3 months 5. 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 4 cycles), completed at least 6 months prior to first documented disease progression will remain eligible 8. No prior radiotherapy within 1 month prior to registration or involving more than 30% of total bone marrow volume 9. No investigational drug within 1 month prior to registration 10. Adequate renal function (GFR >60mL/min, uncorrected for surface area and measured by isotopic means) 11. Adequate bone marrow function (absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L; Plts greater than or equal to 100 x 109/L at baseline) 12. Adequate liver function (Bili less than or equal to 1.5x ULN; ALT and 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 |
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E.4 | Principal exclusion criteria |
1. Patients with urothelial 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 CNS metastases − routine baseline 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. Women of childbearing potential must have a negative pregnancy test performed within 7 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 6 months, congestive cardiac failure >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 medications which have known adverse interactions with the trial treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is activity defined as progression−free survival at 6 months from date of enrolment. This is the proportion of patients who are alive at six months without disease progression, according to Response Evaluation Criteria in Solid Tumours (RECIST). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For the purpose of complying with UK Medicines for Human Use (Clinical Trial) Regulations introduced in May 2004, the trial will be considered closed when the last participant has completed protocol treatment. However, further observational follow up will continue for a minimum of one year. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |