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

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

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.

Study Overview

• Status: Terminated
• Conditions: Transitional Cell Carcinoma of the Bladder
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cisplatin; Drug: Sunitinib Malate; Procedure: Radical Cystectomy

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • St. Bartholomew's Hospital (Barts)
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Treatment; Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy	Drug: Gemcitabine; Gemcitabine ( 1000 mg/m2) IV days 1 and 8; Drug: Cisplatin; Cisplatin (70 mg/m2) IV day 1; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate.	number of participants with a pCR	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Profile	Evaluate the safety profile of Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy in participants with TCC	18 months
Objective Response Rate	To determine the objective response rate for patients with measurable disease according to RECIST.	18 months
Progression Free Survival		18 months
Correlate Biomarker Expression	To evaluate the impact of sunitinib malate in combination with cisplatin and gemcitabine on expression of selected biomarkers.	18 months

Collaborators and Investigators

• Sponsor: Noah Hahn, M.D.
• Collaborators: Pfizer; Hoosier Cancer Research Network

Publications and helpful links

General Publications

• 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.

Helpful Links

• Hoosier Oncology Group Homepage

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 10, 2009
• First Posted (Estimate): March 11, 2009

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: March 15, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: TCC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Gemcitabine; Cisplatin; Sunitinib
• Other Study ID Numbers: HOG GU07-123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No