Gemzar, Cisp, Sunitinib Urothelial Ca

Urothelial Cancer Clinical Trial

Official title:

Phase II Trial of Gemcitabine, Cisplatin, and Sunitinib in Patients With Advanced/Metastatic Urothelial Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00821327
• Other study ID #: 06040
• Secondary ID: WS356467
• Status: Completed
• Phase: Phase 2
• First received: January 9, 2009
• Last updated: February 2, 2016
• Start date: August 2008
• Est. completion date: August 2012

Study information

• Verified date: February 2016
• Source: US Oncology Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Urothelial Cancer

Intervention

Drug:
• Gemcitabine, Cisplatin, Sunitinib
Patients will receive gemcitabine 800 mg/m2 IV (Days 1 and 8), cisplatin 60 mg/m2 IV (Day 1), and sunitinib 37.5 mg PO daily (Days 1-14) of each 21-day cycle. 2. One cycle of treatment is defined as 21 days (3 weeks). Restaging studies will be performed after every 3 cycles of therapy. 3. Successive cycles will be initiated every 3 weeks, and will be continued through 6 cycles unless a patient shows evidence of disease progression or intolerable toxicity.

Locations

Country	Name	City	State
United States	Texas Cancer Center - Abilene	Abilene	Texas
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Texas Oncology, P.A. -Amarillo	Amarillo	Texas
United States	Texas Cancer Center	Arlington	Texas
United States	Texas Oncology - Round Rock Cancer Center	Austin	Texas
United States	Mamie McFaddin Ward Cancer Center, Texas Oncology	Beaumont	Texas
United States	Texas Oncology, P.A. - Bedford	Bedford	Texas
United States	Highline Medical Oncology	Burien	Washington
United States	Hematology Oncology Associates of Illinois	Chicago	Illinois
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Texas Oncology	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Texas Oncology/Methodist Charlton Cancer Ctr.	Dallas	Texas
United States	Texas Cancer Center	Denton	Texas
United States	Pudget Sound Cancer Center	Edmonds	Washington
United States	El Paso Cancer Treatment Center - East	El Paso	Texas
United States	Texas Oncology	Fort Worth	Texas
United States	Texas Oncology	Garland	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Medical Oncology Associates of Wyoming Valley, PC	Kingston	Pennsylvania
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Longview Cancer Center	Longview	Texas
United States	South Texas Cancer Center	McAllen	Texas
United States	Advanced Medical Specialties	Miami	Florida
United States	Texas Oncology, PA, Allison Cancer Center	Midland	Texas
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Hematology-Oncology Associates of Northern NJ, PA	Morristown	New Jersey
United States	Florida Cancer Institute - New Hope	New Port Richey	Florida
United States	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	Raleigh Hematology Oncology Associates	Raleigh	North Carolina
United States	Oncology & Hematology Associates of Southwest Virginia, Inc.	Salem	Virginia
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Cancer Care Centers of South Texas-HOAST	San Antonio	Texas
United States	New Mexico Cancer Care Associates	Santa Fe	New Mexico
United States	Texas Cancer Center - Sherman	Sherman	Texas
United States	Cancer Care Northwest	Spokane	Washington
United States	Willamette Valley Cancer Center	Springfield	Oregon
United States	Arch Medical Services, Inc.	St. Louiis	Missouri
United States	Texas Oncology Cancer Center - Sugar Land	Sugar Land	Texas
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists, PC	Vancouver	Washington
United States	Texas Oncology Cancer Care and Research Center	Waco	Texas
United States	Deke Slayton Cancer Center	Webster	Texas
United States	Alliance Hematology Oncology PA.	Westminster	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
US Oncology Research	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR, CR+PR) in Patients With Advanced/Metastatic UC Treated With the Combination of Gemcitabine, Cisplatin, and Sunitinib.	Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.	2 years	No
Secondary	Progression-free Survival	PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date	2 years	Yes
Secondary	Ovarall Survival (OS)	OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.	2 years	No