Gemzar, Cisp, Sunitinib Urothelial Ca

• Sponsor: US Oncology Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00821327
• Collaborator: Pfizer (Industry)
• Enrollment: 36
• Locations: 48
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urothelial Cancer	Drug: Gemcitabine, Cisplatin, Sunitinib	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Gemcitabine, Cisplatin, and Sunitinib in Patients With Advanced/Metastatic Urothelial Carcinoma
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Study Arm Gemcitabine, Cisplatin, Sunitinib

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.; Other Names: Gemzar, Sutent

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR, CR+PR) in Patients With Advanced/Metastatic UC Treated With the Combination of Gemcitabine, Cisplatin, and Sunitinib. [2 years]

   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.

Secondary Outcome Measures

1. Progression-free Survival [2 years]

   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. Progression (PD) is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

2. Ovarall Survival (OS) [2 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates	Tucson	Arizona	United States	85704
2	Advanced Medical Specialties	Miami	Florida	United States	33176
3	Florida Cancer Institute - New Hope	New Port Richey	Florida	United States	34655
4	Cancer Centers of Florida, P.A.	Ocoee	Florida	United States	34761
5	Hematology Oncology Associates of Illinois	Chicago	Illinois	United States	60611
6	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois	United States	60714
7	Central Indiana Cancer Centers	Indianapolis	Indiana	United States	46227
8	Alliance Hematology Oncology PA.	Westminster	Maryland	United States	21157
9	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota	United States	55404
10	Missouri Cancer Associates	Columbia	Missouri	United States	65201
11	Arch Medical Services, Inc.	St. Louiis	Missouri	United States	63141
12	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
13	Hematology-Oncology Associates of Northern NJ, PA	Morristown	New Jersey	United States	07962
14	New Mexico Cancer Care Associates	Santa Fe	New Mexico	United States	87505
15	New York Oncology Hematology, P.C.	Albany	New York	United States	12206
16	Raleigh Hematology Oncology Associates	Raleigh	North Carolina	United States	27607
17	Willamette Valley Cancer Center	Springfield	Oregon	United States	97477
18	Medical Oncology Associates of Wyoming Valley, PC	Kingston	Pennsylvania	United States	18704
19	Cancer Centers of the Carolinas	Greenville	South Carolina	United States	29605
20	Texas Cancer Center - Abilene	Abilene	Texas	United States	79606
21	Texas Oncology, P.A. -Amarillo	Amarillo	Texas	United States	79106
22	Texas Cancer Center	Arlington	Texas	United States	76014
23	Texas Oncology - Round Rock Cancer Center	Austin	Texas	United States	78731
24	Mamie McFaddin Ward Cancer Center, Texas Oncology	Beaumont	Texas	United States	77702
25	Texas Oncology, P.A. - Bedford	Bedford	Texas	United States	76022
26	Texas Oncology	Dallas	Texas	United States	75230
27	Texas Oncology/Methodist Charlton Cancer Ctr.	Dallas	Texas	United States	75237
28	Texas Oncology, P.A.	Dallas	Texas	United States	75246
29	Texas Cancer Center	Denton	Texas	United States	76210
30	El Paso Cancer Treatment Center - East	El Paso	Texas	United States	79915
31	Texas Oncology	Fort Worth	Texas	United States	76104
32	Texas Oncology	Garland	Texas	United States	75042-5788
33	Longview Cancer Center	Longview	Texas	United States	75601
34	South Texas Cancer Center	McAllen	Texas	United States	78503
35	Texas Oncology, PA, Allison Cancer Center	Midland	Texas	United States	79701
36	Cancer Care Centers of South Texas	San Antonio	Texas	United States	78217
37	Cancer Care Centers of South Texas-HOAST	San Antonio	Texas	United States	78229
38	Texas Cancer Center - Sherman	Sherman	Texas	United States	75090
39	Texas Oncology Cancer Center - Sugar Land	Sugar Land	Texas	United States	77479
40	Tyler Cancer Center	Tyler	Texas	United States	75702
41	Texas Oncology Cancer Care and Research Center	Waco	Texas	United States	76712
42	Deke Slayton Cancer Center	Webster	Texas	United States	77598
43	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
44	Oncology & Hematology Associates of Southwest Virginia, Inc.	Salem	Virginia	United States	24153
45	Highline Medical Oncology	Burien	Washington	United States	98166
46	Pudget Sound Cancer Center	Edmonds	Washington	United States	98026
47	Cancer Care Northwest	Spokane	Washington	United States	99202
48	Northwest Cancer Specialists, PC	Vancouver	Washington	United States	98684

Sponsors and Collaborators

• US Oncology Research
• Pfizer

Investigators

• Principal Investigator: Guru Sonpavde, MD, US Oncology
• Principal Investigator: Thomas E Hutson, DO, US Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Oncology Research
• ClinicalTrials.gov Identifier: NCT00821327
• Other Study ID Numbers: 06040; WS356467
• First Posted: Jan 13, 2009
• Last Update Posted: Oct 25, 2016
• Last Verified: Sep 1, 2016

• Additional relevant MeSH terms: Gemcitabine; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Study Arm: Advanced/Metastatic UC
Arm/Group Description	Gemcitabine, Cisplatin, Sunitinib 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.
Period Title: Overall Study
STARTED	36
COMPLETED	1
NOT COMPLETED	35

Baseline Characteristics

Arm/Group Title	Study Arm: Advanced/Metastatic UC
Arm/Group Description	Gemcitabine, Cisplatin, Sunitinib 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.
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (9.7)
Sex: Female, Male (Count of Participants)
Female	8 22.2%
Male	28 77.8%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	32 88.9%
Hispanic	2 5.6%
Asian	1 2.8%
Black	1 2.8%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR, CR+PR) in Patients With Advanced/Metastatic UC Treated With the Combination of Gemcitabine, Cisplatin, and Sunitinib.
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All eligible patients who meet the protocol-specified efficacy analyses requirements and who have received at least 1 dose of study drug.

Arm/Group Title	Study Arm: Advanced/Metastatic UC
Arm/Group Description	Gemcitabine, Cisplatin, Sunitinib 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.
Measure Participants	33
Number (95% Confidence Interval) [Percentage of participants]	48.5 134.7%

2. Secondary Outcome

Title	Progression-free Survival
Description	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. Progression (PD) is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Study Arm: Advanced/Metastatic UC
Arm/Group Description	Gemcitabine, Cisplatin, Sunitinib 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.
Measure Participants	36
Median (Full Range) [Month]	8.0

3. Secondary Outcome

Title	Ovarall Survival (OS)
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Study Arm: Advanced/Metastatic UC
Arm/Group Description	Gemcitabine, Cisplatin, Sunitinib 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.
Measure Participants	36
Median (95% Confidence Interval) [months]	13.8

Adverse Events

Time Frame	During the whole treatment period, up to 30 days following last dose.
Adverse Event Reporting Description	For treated patients only, assessed at each treatment visit.
Arm/Group Title	Study Arm: Advanced/Metastatic UC
Arm/Group Description	Gemcitabine, Cisplatin, Sunitinib 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.
All Cause Mortality
	Study Arm: Advanced/Metastatic UC
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Study Arm: Advanced/Metastatic UC
	Affected / at Risk (%)	# Events
Total	7/33 (21.2%)
Blood and lymphatic system disorders
ANEMIA	1/33 (3%)	1
BLOOD PRESSURE INCREASED	1/33 (3%)	1
HEMOGLOBIN DECREASED	1/33 (3%)	1
LYMPHADENOPATHY THORACIC	1/33 (3%)	1
NEUTROPENIA	1/33 (3%)	1
THROMBOCYTOPENIA	1/33 (3%)	1
Infections and infestations
CELLULITIS	1/33 (3%)	1
PANCREATITIS	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	Study Arm: Advanced/Metastatic UC
	Affected / at Risk (%)	# Events
Total	32/33 (97%)
Blood and lymphatic system disorders
ANEMIA	22/33 (66.7%)	78
BLEEDING NOSE	2/33 (6.1%)	2
EDEMA	2/33 (6.1%)	2
LEUCOPENIA	10/33 (30.3%)	40
NEUTROPENIA	30/33 (90.9%)	113
THROMBOCYTOPENIA	24/33 (72.7%)	88
Cardiac disorders
HYPERTENSION	5/33 (15.2%)	8
Gastrointestinal disorders
ABDOMINAL PAIN	2/33 (6.1%)	3
ANOREXIA	8/33 (24.2%)	8
CONSTIPATION	9/33 (27.3%)	10
DEHYDRATION	2/33 (6.1%)	2
DIARRHEA	6/33 (18.2%)	10
GASTROESOPHAGEAL REFLUX	9/33 (27.3%)	9
HICCUP	2/33 (6.1%)	2
NAUSEA	16/33 (48.5%)	22
VOMITING	7/33 (21.2%)	9
General disorders
FATIGUE	18/33 (54.5%)	34
INSOMNIA	3/33 (9.1%)	4
PAIN	4/33 (12.1%)	5
WEIGHT LOSS	4/33 (12.1%)	4
Infections and infestations
MUCOSAL SORES	2/33 (6.1%)	2
Metabolism and nutrition disorders
ALT INCREASED	2/33 (6.1%)	5
AST INCREASED	2/33 (6.1%)	6
CREATININE CLEARANCE DECREASED	2/33 (6.1%)	2
CREATININE SERUM INCREASED	3/33 (9.1%)	4
HYPOMAGNESAEMIA	3/33 (9.1%)	5
Musculoskeletal and connective tissue disorders
MUSCLE WEAKNESS	2/33 (6.1%)	2
Nervous system disorders
DIZZINESS	2/33 (6.1%)	3
HEADACHE	2/33 (6.1%)	2
NEUROPATHY	2/33 (6.1%)	2
Renal and urinary disorders
HEMATURIA	2/33 (6.1%)	2
Respiratory, thoracic and mediastinal disorders
SHORTNESS OF BREATH	7/33 (21.2%)	8
Skin and subcutaneous tissue disorders
ALOPECIA	3/33 (9.1%)	3
HAND-FOOT SYNDROME	3/33 (9.1%)	3
RASH	4/33 (12.1%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.