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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00847015
• Collaborator: Pfizer (Industry)
• Enrollment: 18
• Locations: 5
• Arm: 1
• Duration (Months): 45
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if using the combination of standard chemotherapy (gemcitabine and cisplatin) plus this new targeted pill (sunitinib) can help shrink your tumor before you undergo surgery for your bladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer; Urinary Bladder	Drug: Sunitinib; Drug: Gemcitabine; Drug: cisplatin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Gemcitabine, Cisplatin, and Sunitinib (GC-S) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine, Cisplatin, and Sunitinib 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.	Drug: Sunitinib; Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period.; Drug: Gemcitabine; Gemcitabine 1,000 mg/m^2; Drug: cisplatin; cisplatin 35 mg/m^2 will be administered intravenously on days 1 and 8.

Outcome Measures

Primary Outcome Measures

1. The Pathologic Complete Response Rate (<pT0) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer. [2 years]

   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.

Secondary Outcome Measures

1. The Pathologic Response Rate (<pT2) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer. [2 years]

   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.

2. The Time to Disease Progression in Patients With Muscle Invasive Urothelial Carcinoma of the Bladder Treated With Neoadjuvant GCS Followed by Radical Cystectomy. [2 years]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed muscle invasive transitional cell carcinoma of the bladder at MSKCC.

• Clinical stage T2-T4a N0/X M0 disease.

• Medically appropriate candidate for radical cystectomy as per MSKCC attending urologic oncologist.

• Karnofsky Performance Status ≥ 70%.

• Age ≥ 18 years of age.

• Required Initial Laboratory Values:

• Absolute neutrophil count ≥ 1500 cells/mm3

• Platelets ≥ 100,000 cells/mm3

• Hemoglobin ≥ 9.0g/dL

• Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution

• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution

• Alkaline phosphatase ≤ 2.5 x ULN for the institution

• Serum creatinine ≤ 1.5 mg/dL

• Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 using the CKD-EPI equation:

• eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age

• x 1.018 [if female] x 1.159 [if black]

• Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1.

• If female of childbearing potential, pregnancy test is negative.

• Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial.

Exclusion Criteria:

• Prior systemic chemotherapy (prior intravesical therapy is allowed)

• Prior radiation therapy to the bladder

• Evidence of NYHA functional class III or IV heart disease.

• Serious intercurrent medical or psychiatric illness, including serious active infection.

• Preexisting sensory grade 3 neuropathy

• Major surgery or radiation therapy < 4 weeks of starting study treatment.

• Concomitant use of any other investigational drugs

• 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.

• Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥ 2.

• Prolonged QTc interval on baseline EKG (>450 msec for males and >470 msec for females).

• Uncontrolled hypertension (>150/100 mmHg despite optimal medical therapy).

• Pre-existing thyroid abnormality, with thyroid function tests that cannot be maintained in the normal range with medication.

• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection.

• Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.

• Ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg po daily for thromboembolic prophylaxis is allowed).

• Pregnancy or breast-feeding. 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 principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering at Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan-Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
3	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
4	Memorial Sloan-Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York	United States	11570
5	Memoral Sloan Kettering Cancer Center@Phelps	Sleepy Hollow	New York	United States

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Pfizer

Investigators

• Principal Investigator: Dean Bajorin, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00847015
• Other Study ID Numbers: 08-159
• First Posted: Feb 19, 2009
• Last Update Posted: Feb 29, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: Bladder; Urinary; CISPLATIN; GEMCITABINE; SU011248 (Sunitinib Malate); 08-159
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Gemcitabine; Sunitinib

Study Results

Participant Flow

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

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 Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 61.1%
>=65 years	7 38.9%
Sex: Female, Male (Count of Participants)
Female	3 16.7%
Male	15 83.3%
Region of Enrollment (participants) [Number]
United States	18 100%

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.
Measure Participants	15
Number (95% Confidence Interval) [percentage of participants]	6.67 37.1%

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.
Measure Participants	15
Number (95% Confidence Interval) [percentage of participants]	33 183.3%

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.
Measure Participants	15
Median (95% Confidence Interval) [months]	10

Adverse Events

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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine, Cisplatin, and Sunitinib
	Affected / at Risk (%)	# Events
Total	14/18 (77.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	2/18 (11.1%)	2
Anemia	2/18 (11.1%)	2
General disorders
Fever	2/18 (11.1%)	2
Infections and infestations
Wound infection	1/18 (5.6%)	1
Skin infection	1/18 (5.6%)	1
Investigations
Neutrophil count decrease	1/18 (5.6%)	1
Platelet count decreased	4/18 (22.2%)	5
Metabolism and nutrition disorders
Hyponatremia	1/18 (5.6%)	1
Dehydration	1/18 (5.6%)	1
Nervous system disorders
Syncope	1/18 (5.6%)	1
Vascular disorders
Hypotension	1/18 (5.6%)	1
Thrombosis	2/18 (11.1%)	2
Other (Not Including Serious) Adverse Events
	Gemcitabine, Cisplatin, and Sunitinib
	Affected / at Risk (%)	# Events
Total	18/18 (100%)
Blood and lymphatic system disorders
Anemia	11/18 (61.1%)	11
Febrile Neutropenia	2/18 (11.1%)	2
Cardiac disorders
Leukocytes (total WBC)	6/18 (33.3%)	25
General disorders
Fatigue (asthenia, lethargy, malaise)	2/18 (11.1%)	2
Infections and infestations
Infection	2/18 (11.1%)	2
Investigations
Neutrophil count decreased	6/18 (33.3%)	6
Lymphopenia	3/18 (16.7%)	5
Neutrophils/granulocytes (ANC/AGC)	6/18 (33.3%)	34
Platelets	6/18 (33.3%)	16
Metabolism and nutrition disorders
Glucose, high (hyperglycemia)	8/18 (44.4%)	18
Magnesium, low (hypomagnesemia)	2/18 (11.1%)	3
Potassium, high (hyperkalemia)	2/18 (11.1%)	3
Renal and urinary disorders
Urinary frequency/urgency	5/18 (27.8%)	7
Vascular disorders
Thrombotic events	2/18 (11.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.