Gemzar, Cisp, Sunitinib Urothelial Ca

NCT ID: NCT00821327

Last Updated: 2016-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2012-08-31

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.

Conditions

Urothelial Cancer

Study Design

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

Study Groups

Study Arm

Gemcitabine, Cisplatin, Sunitinib

Group Type: EXPERIMENTAL

Gemcitabine, Cisplatin, Sunitinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Gemzar, Sutent

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

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

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

US Oncology Research

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guru Sonpavde, MD

Role: PRINCIPAL_INVESTIGATOR

US Oncology

Thomas E Hutson, DO

Role: PRINCIPAL_INVESTIGATOR

US Oncology

Locations

Arizona Oncology Associates

Tucson, Arizona, United States

Advanced Medical Specialties

Miami, Florida, United States

Florida Cancer Institute - New Hope

New Port Richey, Florida, United States

Cancer Centers of Florida, P.A.

Ocoee, Florida, United States

Hematology Oncology Associates of Illinois

Chicago, Illinois, United States

Cancer Care & Hematology Specialists of Chicagoland

Niles, Illinois, United States

Central Indiana Cancer Centers

Indianapolis, Indiana, United States

Alliance Hematology Oncology PA.

Westminster, Maryland, United States

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, United States

Missouri Cancer Associates

Columbia, Missouri, United States

Arch Medical Services, Inc.

Saint Louiis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Hematology-Oncology Associates of Northern NJ, PA

Morristown, New Jersey, United States

New Mexico Cancer Care Associates

Santa Fe, New Mexico, United States

New York Oncology Hematology, P.C.

Albany, New York, United States

Raleigh Hematology Oncology Associates

Raleigh, North Carolina, United States

Willamette Valley Cancer Center

Springfield, Oregon, United States

Medical Oncology Associates of Wyoming Valley, PC

Kingston, Pennsylvania, United States

Cancer Centers of the Carolinas

Greenville, South Carolina, United States

Texas Cancer Center - Abilene

Abilene, Texas, 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

Texas Oncology

Dallas, Texas, United States

Texas Oncology/Methodist Charlton Cancer Ctr.

Dallas, Texas, United States

Texas Oncology, P.A.

Dallas, Texas, United States

Texas Cancer Center

Denton, Texas, 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

Longview Cancer Center

Longview, Texas, United States

South Texas Cancer Center

McAllen, Texas, United States

Texas Oncology, PA, Allison Cancer Center

Midland, Texas, 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

Texas Cancer Center - Sherman

Sherman, Texas, United States

Texas Oncology Cancer Center - Sugar Land

Sugar Land, Texas, United States

Tyler Cancer Center

Tyler, Texas, United States

Texas Oncology Cancer Care and Research Center

Waco, Texas, United States

Deke Slayton Cancer Center

Webster, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Oncology & Hematology Associates of Southwest Virginia, Inc.

Salem, Virginia, United States

Highline Medical Oncology

Burien, Washington, United States

Pudget Sound Cancer Center

Edmonds, Washington, United States

Cancer Care Northwest

Spokane, Washington, United States

Northwest Cancer Specialists, PC

Vancouver, Washington, United States

Countries

United States

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)

Other Identifiers

WS356467

Identifier Type: OTHER

Identifier Source: secondary_id

06040

Identifier Type: -

Identifier Source: org_study_id