Gemcitabine, Cisplatin, and Sunitinib (GC-S) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer

• ClinicalTrials.gov Identifier: NCT00847015
• Recruitment Status: Completed
• First Posted: February 19, 2009
• Results First Posted: February 29, 2016
• Last Update Posted: February 29, 2016
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: Pfizer
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Bladder Cancer; Urinary Bladder
• Interventions: Drug: Sunitinib; Drug: Gemcitabine; Drug: cisplatin
• Enrollment: 18

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Gemcitabine, Cisplatin, and Sunitinib
Arm/Group Description	This is a phase II study of GCS (Gemcitabine, Cisplatin, and Sunitinib) as neoadjuvant chemotherapy in patients with muscle-invasive urothelial carcinoma of the bladder. Patients with muscle invasive urothelial carcinoma who are candidates for radical cystectomy will be enrolled. Gemcitabine, Cisplatin, and Sunitinib: Patients will receive four cycles of GCS administered every 21 days followed by radical cystectomy. Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period. Gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8.
Period Title: Overall Study
Started	18
Completed	15
Not Completed	3
Reason Not Completed
Withdrawal by Subject	1
declined any surgery	1
partial cystectomy vs radical cystectomy	1

Baseline Characteristics

Arm/Group Title		Gemcitabine, Cisplatin, and Sunitinib
Arm/Group Description		This is a phase II study of GCS (Gemcitabine, Cisplatin, and Sunitinib) as neoadjuvant chemotherapy in patients with muscle-invasive urothelial carcinoma of the bladder. Patients with muscle invasive urothelial carcinoma who are candidates for radical cystectomy will be enrolled. Gemcitabine, Cisplatin, and Sunitinib: Patients will receive four cycles of GCS administered every 21 days followed by radical cystectomy. Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period. Gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8.
Overall Number of Baseline Participants		18
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	11 61.1%
	>=65 years	7 38.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	Female	3 16.7%
	Male	15 83.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	18 participants
		18

Outcome Measures

1. Primary Outcome

Title	The Pathologic Complete Response Rate (<pT0) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer.
Description	Complete pathologic response to neoadjuvant GCS is the primary endpoint is defined as the absence of carcinoma (pT0 disease) and the absence of microscopic lymph node metastases (N0) on the final cystectomy specimen.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Cisplatin, and Sunitinib
Arm/Group Description:	This is a phase II study of GCS (Gemcitabine, Cisplatin, and Sunitinib) as neoadjuvant chemotherapy in patients with muscle-invasive urothelial carcinoma of the bladder. Patients with muscle invasive urothelial carcinoma who are candidates for radical cystectomy will be enrolled. Gemcitabine, Cisplatin, and Sunitinib: Patients will receive four cycles of GCS administered every 21 days followed by radical cystectomy. Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period. Gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8.
Overall Number of Participants Analyzed	15
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	6.67; (.34 to 29.8)

2. Secondary Outcome

Title	The Pathologic Response Rate (<pT2) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer.
Description	is defined as the absence of muscle invasive carcinoma (<pT2 disease) and the absence of microscopic lymph node metastases (N0) on the final cystectomy specimen.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Cisplatin, and Sunitinib
Arm/Group Description:	This is a phase II study of GCS (Gemcitabine, Cisplatin, and Sunitinib) as neoadjuvant chemotherapy in patients with muscle-invasive urothelial carcinoma of the bladder. Patients with muscle invasive urothelial carcinoma who are candidates for radical cystectomy will be enrolled. Gemcitabine, Cisplatin, and Sunitinib: Patients will receive four cycles of GCS administered every 21 days followed by radical cystectomy. Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period. Gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8.
Overall Number of Participants Analyzed	15
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	33; (15 to 58)

3. Secondary Outcome

Title	The Time to Disease Progression in Patients With Muscle Invasive Urothelial Carcinoma of the Bladder Treated With Neoadjuvant GCS Followed by Radical Cystectomy.
Description	The time to disease progression is measured from the time of initiation of chemotherapy until the first date that systemic recurrence is objectively documented. Systemic recurrence for this trial is defined as either metastatic or local pelvic recurrence.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Cisplatin, and Sunitinib
Arm/Group Description:	This is a phase II study of GCS (Gemcitabine, Cisplatin, and Sunitinib) as neoadjuvant chemotherapy in patients with muscle-invasive urothelial carcinoma of the bladder. Patients with muscle invasive urothelial carcinoma who are candidates for radical cystectomy will be enrolled. Gemcitabine, Cisplatin, and Sunitinib: Patients will receive four cycles of GCS administered every 21 days followed by radical cystectomy. Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period. Gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8.
Overall Number of Participants Analyzed	15
Median (95% Confidence Interval); Unit of Measure: months
	10 [1]; (3.5 to NA)

[1]

This number could not be calculated as three participants are deceased.

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Gemcitabine, Cisplatin, and Sunitinib
Arm/Group Description	This is a phase II study of GCS (Gemcitabine, Cisplatin, and Sunitinib) as neoadjuvant chemotherapy in patients with muscle-invasive urothelial carcinoma of the bladder. Patients with muscle invasive urothelial carcinoma who are candidates for radical cystectomy will be enrolled. Gemcitabine, Cisplatin, and Sunitinib: Patients will receive four cycles of GCS administered every 21 days followed by radical cystectomy. Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period. Gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8.
All-Cause Mortality
	Gemcitabine, Cisplatin, and Sunitinib
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Gemcitabine, Cisplatin, and Sunitinib
	Affected / at Risk (%)	# Events
Total	14/18 (77.78%)
Blood and lymphatic system disorders
Febrile Neutropenia † 1	2/18 (11.11%)	2
Anemia † 2	2/18 (11.11%)	2
General disorders
Fever † 2	2/18 (11.11%)	2
Infections and infestations
Wound infection † 2	1/18 (5.56%)	1
Skin infection † 2	1/18 (5.56%)	1
Investigations
Neutrophil count decrease † 2	1/18 (5.56%)	1
Platelet count decreased † 2	4/18 (22.22%)	5
Metabolism and nutrition disorders
Hyponatremia † 2	1/18 (5.56%)	1
Dehydration † 2	1/18 (5.56%)	1
Nervous system disorders
Syncope † 2	1/18 (5.56%)	1
Vascular disorders
Hypotension † 2	1/18 (5.56%)	1
Thrombosis † 2	2/18 (11.11%)	2
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, ctcae 3.0; 2 Term from vocabulary, CTCAE (3.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Gemcitabine, Cisplatin, and Sunitinib
	Affected / at Risk (%)	# Events
Total	18/18 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	11/18 (61.11%)	11
Febrile Neutropenia † 1	2/18 (11.11%)	2
Cardiac disorders
Leukocytes (total WBC) † 1	6/18 (33.33%)	25
General disorders
Fatigue (asthenia, lethargy, malaise) † 1	2/18 (11.11%)	2
Infections and infestations
Infection † 1	2/18 (11.11%)	2
Investigations
Neutrophil count decreased † 1	6/18 (33.33%)	6
Lymphopenia † 1	3/18 (16.67%)	5
Neutrophils/granulocytes (ANC/AGC) † 1	6/18 (33.33%)	34
Platelets † 1	6/18 (33.33%)	16
Metabolism and nutrition disorders
Glucose, high (hyperglycemia) † 1	8/18 (44.44%)	18
Magnesium, low (hypomagnesemia) † 1	2/18 (11.11%)	3
Potassium, high (hyperkalemia) † 1	2/18 (11.11%)	3
Renal and urinary disorders
Urinary frequency/urgency † 1	5/18 (27.78%)	7
Vascular disorders
Thrombotic events † 1	2/18 (11.11%)	2
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE (3.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. M. Catherine Pietanza
• Organization: Memorial Sloan Kettering Cancer Center
• Phone: 646-888-4203
• EMail: pietanzm@mskcc.org

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00847015
• Other Study ID Numbers: 08-159
• First Submitted: February 18, 2009
• First Posted: February 19, 2009
• Results First Submitted: October 19, 2015
• Results First Posted: February 29, 2016
• Last Update Posted: February 29, 2016