E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
operable bladder cancer (T2 to T4a) lymph node negative disease |
|
MedDRA Classification |
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 |
Primary Objective: To determine the pathological complete response rate at cystectomy after four cycles of neoadjuvent Gemcitabine/Cisplatin/Sunitinib therapy in operable bladder cancer.
|
|
E.2.2 | Secondary objectives of the trial |
Secondary Objective:
•To evaluate the safety profile of sunitinib malate in combination with cisplatin and gemcitabine followed by radical cystectomy. •To determine the objective response rate for patients with measurable disease according to RECIST. •To determine progression free survival. •To evaluate the impact of sunitinib malate in combination with cisplatin and gemcitabine on expression of selected biomarkers.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Written informed consent for release of personal health information.
•Age > 18 years at the time of consent.
•ECOG Performance Status of 0-1 within 14 days prior to registration for protocol therapy.
•Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation.
•Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
•Females must not be breastfeeding.
•Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III) with no evidence of metastatic disease (focal squamous and/or adenocarcinoma differentiation allowed, sarcomatoid and small-cell components not allowed). Patient with any degree of fixation of the pelvic sidewall are not eligible.
•Must be willing to undergo a cystoscopy if tumor block is not available prior to registration for protocol therapy.
•Eligible for radical cystectomy as per the attending urologist.
•No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 5 years.
•No treatment with any investigational agent within 30 days prior to registration for protocol therapy.
•No prior radiotherapy to the pelvis.
•Prior radiation therapy to bone marrow is allowed to < 25% of the marrow, and must be completed at least 6 months prior to registration for protocol therapy.
NOTE: Laboratory values must be obtained within 14 days prior to registration for protocol therapy.
•Total bilirubin < 1.5 x Upper Limit of Normal (ULN)
•Aspartate aminotransferase (AST) ≤ 2.5 x ULN
•Alanine aminotransferase (ALT ) ≤ 2.5 x ULN
•Calculated creatinine clearance of ≥60 cc/min as calculated with Cockroft-Gault equation.
• Absolute Neutrophil Count (ANC) > 1.5 K/mm3 [International Sites (IS): 1.5 x 109/L].
• Platelets > 100 K/mm3 [IS: 100 x 109/L].
• Hemoglobin (Hgb) > 9.0 g/dL [IS: 90 g/L].
• Patients on warfarin (>2mg) for thrombosis must be able and willing to switch to low molecular weight heparin prior to registration for protocol therapy.
• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the patient has been disease free for at least 5 years. |
|
E.4 | Principal exclusion criteria |
• Any prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the patient has been diseasefree for at least 5 years. • Any surgical procedure less than 2 weeks prior to registration for protocol therapy. • Treatment with any investigational agent within 30 days prior to registration for protocol therapy. • Prior radiotherapy to the pelvis. • Clinically significant infections as judged by the treating investigator. • Evidence of NCI CTCAE Version 3.0 grade 3 hemorrhage within 28 days prior to registration for protocol therapy (excluding resolved hematuria). • Uncontrolled angina, congestive heart failure or myocardial infarction or coronary/peripheral artery bypass graft within 6 months prior to registration for protocol therapy. • Cerebrovascular accident or transient ischemic attack within 6 months prior to registration for protocol therapy. • Evidence of pulmonary embolism within 6 months prior to registration for protocol therapy. • Uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy). • Evidence of ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade 2. • History of uncontrolled/untreated thyroid dysfunction. • Prolonged QTc interval (>450 msec) on preentry electrocardiogram obtained within 28 days prior to registration for protocol therapy. • Use of drugs having proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide) within 7 days prior to registration for protocol therapy. • Use of CYP3A4 inhibitors within 7 days of registration for protocol therapy (ketoconazole, itraconazole, voriconazole, fluconazole, troleandomycin, clarithromycin, erythromycin, diltiazem, verapamil, delavirdine, amprenavir, lopinivir, indinavir, saquinavir, ritonavir, nelfinavir, nefazodone, fluvoxamine, cimetidine, aprepitant). • Use of CYP3A4 inducers within 14 days of registration for protocol therapy (rifampicin, rifabutin, rifapentine, carbamazepine, phenobarbital, phenytoin, St John’s Wort, modafinil, efavirenz, nevirapine, cortisone (>50 mg), hydrocortisone (>40mg), prednisone (>10 mg), methylprednisolone (>8 mg), dexamethasone (>1.5 mg)2). • Use of amiodarone (CYP3A4 inhibitor) within 6 months of registration for protocol therapy.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint: To determine the pathological complete response rate associated with neoadjuvent Gemcitibine, cisplatin and sunitinib therapy. This will be assessed at the time of cystectomy.
|
|
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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 2 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
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
|
This clinical trial will end 3 years after the last consent form has been signed. From there, patients will be followed up according to standard clinical care protocols.. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |