Clinical trial NCT00859339: Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC
Official title: A Phase II Trial of Neoadjuvant Cisplatin, Gemcitabine and Sunitinib Malate Followed by Radical Cystectomy for Transitional Cell Carcinoma (TCC) of the Bladder: Hoosier Oncology Group GU07-123
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Transitional Cell Carcinoma of the Bladder
Keywords: TCC
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Hoosier Cancer Research Network
First posted: 2009-03-11
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial will investigate the activity of sunitinib combined with cisplatin and gemcitabine followed by radical cystectomy in patients with Transitional Cell Carcinoma (TCC) of the Bladder.

Detailed description: OUTLINE: This is a multi-center study.

* Gemcitabine ( 1000 mg/m2) IV days 1 and 8
* Cisplatin (70 mg/m2) IV day 1 and
* Sunitinib malate (37.5 mg) oral daily for days 1-14

The treatment regimen will be administered in four, 21-day, cycles followed by radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.

ECOG performance status 0 or 1

Hematopoietic:

* Absolute Neutrophil Count (ANC) \> 1.5 K/mm3 \[(IS): 1.5 x 109/L\]
* Platelets \> 100 K/mm3 \[(IS): 100 x 109/L\]
* Hemoglobin (Hgb) \> 9.0 g/dL \[(IS): 90 g/L\]

Hepatic:

* Total bilirubin \< 1.5 x Upper Limit of Normal (ULN)
* Aspartate aminotransferase (AST) ≤ 2.5 x ULN
* Alanine aminotransferase (ALT) ≤ 2.5 x ULN

Renal:

* Calculated creatinine clearance of \> 60 cc/min

Cardiovascular:

* No uncontrolled angina, congestive heart failure or myocardial infarction or coronary/peripheral artery bypass graft within 6 months prior to registration for protocol therapy.

Eligibility criteria: Inclusion Criteria:

* 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.
* 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
* Written informed consent and HIPAA authorization for release of personal health information.
* Age \> 18 years at the time of consent.
* 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.

Exclusion Criteria:

* No prior radiotherapy to the pelvis.
* 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 cerebrovascular accident or transient ischemic attack within 6 months prior to registration for protocol therapy.
* No evidence of pulmonary embolism within 6 months prior to registration for protocol therapy.
* No uncontrolled hypertension (\>150/100 mm Hg despite optimal medical therapy).
* No evidence of ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade 2.
* No history of uncontrolled/untreated thyroid dysfunction.
* No prolonged QTc interval (\> 450 msec) on pre-entry electrocardiogram obtained within 28 days prior to being registered on study.
* 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 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.
* No use of CYP3A4 inhibitors (see section 5.3 for a list) within 7 days of registration for protocol therapy.
* No use of CYP3A4 inducers (see section 5.3 for a list) within 14 days of registration for protocol therapy.
* No use of amiodarone (CYP3A4 inhibitor) within 6 months of registration for protocol therapy.
* Females must not be breastfeeding.

Primary outcomes:
measure: Pathological Complete Response (pCR) Rate.
timeFrame: 18 months
Secondary outcomes:
measure: Safety Profile
timeFrame: 18 months
measure: Objective Response Rate
timeFrame: 18 months
measure: Progression Free Survival
timeFrame: 18 months
measure: Correlate Biomarker Expression
timeFrame: 18 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital (Barts)
Study officials:
affiliation: Hoosier Cancer Research Network
name: Noah Hahn, M.D.
role: STUDY_CHAIR
References:
citation: Galsky MD, Hahn NM, Powles T, Hellerstedt BA, Lerner SP, Gardner TA, Yu M, O'Rourke M, Vogelzang NJ, Kocs D, McKenney SA, Melnyk AM Jr, Hutson TE, Rauch M, Wang Y, Asmar L, Sonpavde G. Gemcitabine, Cisplatin, and sunitinib for metastatic urothelial carcinoma and as preoperative therapy for muscle-invasive bladder cancer. Clin Genitourin Cancer. 2013 Jun;11(2):175-81. doi: 10.1016/j.clgc.2012.10.001. Epub 2012 Dec 8.