Clinical trial NCT00821327: Gemzar, Cisp, Sunitinib Urothelial Ca
Official title: Phase II Trial of Gemcitabine, Cisplatin, and Sunitinib in Patients With Advanced/Metastatic Urothelial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urothelial Cancer
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2009-01-13
Enrollment: 36
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: The primary objective of this nonrandomized Phase II study is to evaluate the objective response rate (ORR, CR+PR) in patients with advanced/metastatic UC treated with the combination of gemcitabine, cisplatin, and sunitinib.

Detailed description: Given the strong preclinical rationale for targeting angiogenesis in urothelial carcinoma (UC), the evidence supporting co-targeting of VEGFR2 and PDGF, the safety and efficacy of single-agent sunitinib in patients with UC, and preclinical evidence of synergy with the combination of sunitinib and cisplatin, the evaluation of sunitinib in combination with gemcitabine plus cisplatin in previously untreated patients with metastatic UC is warranted.

Eligibility criteria: Inclusion Criteria:

1. Has histological documentation of diagnosis of transitional cell carcinoma (TCC) of the bladder, urethra, ureter, or renal pelvis (histology may be mixed, but still requires a component of TCC; measurable disease only)
2. Has unresectable or metastatic disease
3. Has a Karnofsky Performance Status greater than or equal 60 percent
4. Is 18 years of age or older
5. Has laboratory values as defined by the protocol
6. Has resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI CTCAE (v3.0) Grade less than or equal to 1
7. Has normal cardiac function as evidenced by a LVEF greater than or equal to 50 percent, as determined by multiple gated acquisition (MUGA) scan or an echocardiogram (ECHO). The same method must be used throughout the study to evaluate LVEF.
8. Has a negative serum pregnancy test within 7 calendar days prior to registration (female patients of childbearing potential \[not surgically sterilized and between menarche and 1 year postmenopausal\])
9. Is not currently breastfeeding
10. If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of 3 months thereafter.
11. Has signed a Patient Informed Consent Form, Has signed a Patient Authorization Form

Exclusion Criteria:

1. Has had prior treatment with systemic chemotherapy (prior intravesical therapy is permitted)
2. Has had major surgery or radiation therapy within 4 weeks of starting the study treatment
3. Has had NCI CTCAE (Version 3.0) Grade 3-4 hemorrhage within 4 weeks of starting the study treatment
4. Has a history of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan. However treated, stable and asymptomatic brain metastases are allowed.
5. Has had any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
6. Has ongoing cardiac dysrhythmias of NCI CTCAE (Version 3.0) Grade 2
7. Has prolonged QTc interval on baseline EKG
8. Has uncontrolled hypertension (grater than 150/100 mm Hg despite optimal medical therapy)
9. Has pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
10. Has known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection
11. Is receiving concomitant use of any other investigational drugs or has received such drug within 28 days prior to registration
12. Is receiving concurrent treatment on another clinical trial, including supportive care
13. Has ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg PO daily for thromboembolic prophylaxis allowed). Patients on warfarin (greater than 2mg) for thrombosis must be switched to low molecular weight heparin (ie, Lovenox), prior to registration for protocol therapy.
14. Is currently taking drugs having proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide) within 7 days prior to Day 1 of Cycle 1 (dosing) (and throughout study)
15. Is currently on CYP3A4 inhibitors (see Section 5) within 7 days prior to Day 1 of Cycle 1 (dosing), with the exception of amiodarone, which should be discontinued within 6 months prior to Day 1 of Cycle 1 (dosing)
16. Is currently on CYP3A4 inducers (see Section 5) within 14 days prior to Day 1 of Cycle 1 (dosing)
17. Has been taking herbal or alternative medications within the past 7 days or refuses to discontinue the use of herbal or alternative therapies within 7 days prior to Day 1 of Cycle 1 (dosing)
18. Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection
19. Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs.
20. Is a pregnant or nursing woman. Patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the Study Investigator or Treating Physician. Male patients must be surgically sterile or agree to use effective contraception.

Is unable to comply with requirements of study

Primary outcomes:
measure: Objective Response Rate (ORR, CR+PR) in Patients With Advanced/Metastatic UC Treated With the Combination of Gemcitabine, Cisplatin, and Sunitinib.
timeFrame: 2 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 2 years
measure: Ovarall Survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Miami
country: United States
facility: Advanced Medical Specialties
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute - New Hope
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Chicago
country: United States
facility: Hematology Oncology Associates of Illinois
state: Illinois
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Westminster
country: United States
facility: Alliance Hematology Oncology PA.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: St. Louiis
country: United States
facility: Arch Medical Services, Inc.
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern NJ, PA
state: New Jersey
city: Santa Fe
country: United States
facility: New Mexico Cancer Care Associates
state: New Mexico
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Raleigh
country: United States
facility: Raleigh Hematology Oncology Associates
state: North Carolina
city: Springfield
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Kingston
country: United States
facility: Medical Oncology Associates of Wyoming Valley, PC
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Abilene
country: United States
facility: Texas Cancer Center - Abilene
state: Texas
city: Amarillo
country: United States
facility: Texas Oncology, P.A. -Amarillo
state: Texas
city: Arlington
country: United States
facility: Texas Cancer Center
state: Texas
city: Austin
country: United States
facility: Texas Oncology - Round Rock Cancer Center
state: Texas
city: Beaumont
country: United States
facility: Mamie McFaddin Ward Cancer Center, Texas Oncology
state: Texas
city: Bedford
country: United States
facility: Texas Oncology, P.A. - Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Texas Oncology/Methodist Charlton Cancer Ctr.
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Denton
country: United States
facility: Texas Cancer Center
state: Texas
city: El Paso
country: United States
facility: El Paso Cancer Treatment Center - East
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology
state: Texas
city: Garland
country: United States
facility: Texas Oncology
state: Texas
city: Longview
country: United States
facility: Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: South Texas Cancer Center
state: Texas
city: Midland
country: United States
facility: Texas Oncology, PA, Allison Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas-HOAST
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center - Sherman
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center - Sugar Land
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Waco
country: United States
facility: Texas Oncology Cancer Care and Research Center
state: Texas
city: Webster
country: United States
facility: Deke Slayton Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Salem
country: United States
facility: Oncology & Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Burien
country: United States
facility: Highline Medical Oncology
state: Washington
city: Edmonds
country: United States
facility: Pudget Sound Cancer Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, PC
state: Washington
Study officials:
affiliation: US Oncology
name: Guru Sonpavde, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: US Oncology
name: Thomas E Hutson, DO
role: PRINCIPAL_INVESTIGATOR
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.