Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC

NCT ID: NCT00859339

Last Updated: 2016-04-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2011-04-30

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.

Conditions

Transitional Cell Carcinoma of the Bladder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Treatment

Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Gemcitabine ( 1000 mg/m2) IV days 1 and 8

Cisplatin

Intervention Type: DRUG

Cisplatin (70 mg/m2) IV day 1

Sunitinib Malate

Intervention Type: DRUG

Sunitinib malate (37.5 mg) oral daily for days 1-14

Radical Cystectomy

Intervention Type: PROCEDURE

Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.

Interventions

Gemcitabine

Gemcitabine ( 1000 mg/m2) IV days 1 and 8

Intervention Type: DRUG

Cisplatin

Cisplatin (70 mg/m2) IV day 1

Intervention Type: DRUG

Sunitinib Malate

Sunitinib malate (37.5 mg) oral daily for days 1-14

Intervention Type: DRUG

Radical Cystectomy

Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: collaborator

Noah Hahn, M.D.

OTHER

Sponsor Role: lead

Responsible Party

Noah Hahn, M.D.

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Noah Hahn, M.D.

Role: STUDY_CHAIR

Hoosier Cancer Research Network

Locations

University of Florida

Gainesville, Florida, United States

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Baylor College of Medicine

Houston, Texas, United States

St. Bartholomew's Hospital (Barts)

London, , United Kingdom

Countries

United States; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 23228446 (View on PubMed)

Related Links

http://www.hoosieroncologygroup.org

Hoosier Oncology Group Homepage

Other Identifiers

HOG GU07-123

Identifier Type: -

Identifier Source: org_study_id