Phase II Trial of Neoadjuvent Cisplatin, Gemcitabine and Sunitinib Malate followed by radical cystectomy for transitional Cell Carcinoma (TCC) of the bladder

Active, not recruiting

• Conditions: operable bladder cancer (T2 to T4a) lymph node negative disease

• Registration Number: EUCTR2008-006214-26-GB
• Lead Sponsor: Hoosier Oncology Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-22
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 46

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary Objective:<br>To determine the pathological complete response rate at cystectomy after four cycles of neoadjuvent Gemcitabine/Cisplatin/Sunitinib therapy in operable bladder cancer. <br><br>;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. <br><br>;Secondary Objective: Secondary Objective:<br><br>•To evaluate the safety profile of sunitinib malate in combination with cisplatin and gemcitabine followed by radical cystectomy.<br>•To determine the objective response rate for patients with measurable disease according to RECIST.<br>•To determine progression free survival.<br>•To evaluate the impact of sunitinib malate in combination with cisplatin and gemcitabine on expression of selected biomarkers.<br>