E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically proven advanced TCC (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 | 10044420 |
E.1.2 | Term | Transitional cell carcinoma of the bladder stage unspecified |
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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 |
To determine the tumor response rate of sunitinib in patients with advanced or metastatic transitional cell carcinoma of the urothelium which failed or progressed after first line chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate: 1. Safety (NCI CTC) 2. Time to response, duration of response 3. Tumor imaging in contrast-enhanced color Doppler ultrasonography (optional) 4. Progression free survival 5. Overall survival
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically proven advanced transitional cell carcinoma of the urothelium 2. Progressive disease after one line of chemotherapy for locally advanced or metastatic disease 3. Patients treated with neoadjuvant or adjuvant chemotherapy before may be included if the perioperative chemotherapy was performed at least one year before the chemotherapy for metastatic or loco-regional relapse 4. Previous treatment with a platinum derivative 5. Previous chemotherapy or radiotherapy must have been stopped 30 days before first dose of study treatment and patients must have recovered from any serious side effects of treatment 6. Patients must have one measurable lesion defined by RECIST criteria not previously irradiated, assessed by conventional CT-scan ou MRI performed < 28 days before first day of study drug administration 7. Patient aged 18 years old or more 8. Patients must have a performance Status < 2 on the Eastern Cooperative Oncology Group Scale 9. Adequate haematological function (ANC > 1.5 x 109/L; Platelets ≥ 100 x 109/L and Hb ≥ 8 g/dL) 10. Adequate hepatic function: total bilirubin ≤ 1.5 times the upper limit of normal (ULN) ASAT and ALAT ≤ 2.5 x ULN or ≤ 5 x UNL in presence of liver metastase 11. Adequate renal function: calculated creatinine clearance ≥ 40 ml/min according to Cockcroft and Gault formula 12. Partial thromboplastin time (PTT) ≤ 1.5 x UNL and INR ≤ 1.5 13. Women and men with reproductive potential must use medically acceptable contraceptive method 14. Patients must be affiliated to a Social Security System 15. Patient Information and written informed consent form signed
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E.4 | Principal exclusion criteria |
1. Previous chemotherapy in an adjuvant or neoadjuvant setting only 2. Prior treatment with radiotherapy involving more than 25 % of marrow producing area 3. Concurrent anti-cancer treatment in an another investigational trial 4. Concurrent anti-cancer treatment 5. Prior treatment on sunitinib 6. Uncontrolled high blood pressure defined as >150/100 mm/Hg despite treatment 7. Progressives brain metastases 8. Any of the following within the 12 months prior to study drug administration: a. myocardial infarction, b. severe/unstable angina pectoris, coronary artery bypass graft, c. symptomatic congestive heart failure, d. cerebrovascular accident, e. including transient ischemic attack, f. pulmonary embolism 9. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2, atrial fibrillation of any grade, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females 10. Ongoing active infection 11. Treatment with anticoagulant agents at therapeutic doses currently or within 2 weeks prior to first day of sunitinib administration. Low molecular weight heparin is allowed. 12. NCI CTC Grade 3 hemorrhage < 4 weeks of starting study treatment 13. History of interstitial pneumonitis or pulmonary fibrosis 14. History of deep venous thrombosis within 6 months prior to entry on study 15. Pre-existing neuropathy of NCI CTCAE grade ≥ 2 16. Diagnosis of any second malignancy within the last 5 years, except basal cell carcinoma, squamous cell skin cancer, incidental PT2 prostate cancer found on a radical cystoprostatectomy material; or carcinoma in situ of the cervix that has been adequately treated with no evidence of recurrent disease for 12 months 17. Pregnant women, women who are likely to be pregnant or are breastfeeding 18. Individuals deprived of liberty or placed under the authority of a tutor 19. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and the follow-up
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E.5 End points |
E.5.1 | Primary end point(s) |
The determination of antitumor efficacy will be based on objective tumor assessments made according to the Response Evaluation Criteria in Solid Tumors (RECIST) system of unidimensional evaluation (see Appendix 4). |
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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 | Yes |
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 | 15 |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | |