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

Transitional Cell Carcinoma of the Bladder Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00859339
• Other study ID #: HOG GU07-123
• Status: Terminated
• Phase: Phase 2
• First received: March 9, 2009
• Last updated: August 17, 2015
• Start date: March 2009
• Est. completion date: April 2011

Study information

• Verified date: August 2015
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Transitional Cell Carcinoma of the Bladder
• Urinary Bladder Neoplasms

Intervention

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

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

Locations

Country	Name	City	State
United Kingdom	St. Bartholomew's Hospital (Barts)	London
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana

Sponsors (3)

Lead Sponsor	Collaborator
Noah Hahn, M.D.	Hoosier Cancer Research Network, Pfizer

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the pathological complete response rate.		18 months	No
Secondary	To evaluate the safety profile of sunitinib malate in combination with cisplatin and gemcitabine followed by radical cystectomy.		18 months	Yes
Secondary	To determine the objective response rate for patients with measurable disease according to RECIST.		18 months	No
Secondary	To determine progression free survival.		18 months	No
Secondary	To evaluate the impact of sunitinib malate in combination with cisplatin and gemcitabine on expression of selected biomarkers.		18 months	No

External Links

•   Hoosier Oncology Group Homepage