Sunitinib in Treating Patients With Progressive Metastatic Transitional Cell Cancer of the Urothelium

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00397488
• Collaborator: National Cancer Institute (NCI) (NIH), Pfizer (Industry)
• Enrollment: 78
• Location: 1
• Arm: 1
• Duration (Months): 65
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with progressive metastatic transitional cell cancer of the urothelium.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter; Urethral Cancer	Drug: sunitinib malate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate in patients with progressive metastatic transitional cell carcinoma of the urothelium treated with sunitinib malate.

• Determine the safety of this regimen in these patients.

Secondary

• Determine the time to disease progression in patients treated with this regimen.

• To determine time to tumor progression (TTP) for sunitinib malate on a continuous dosing schedule for treatment of metastatic urothelial carcinoma.

• To estimate sunitinib and SU012662 trough plasma concentration (Ctrough) data for the continuous daily schedule and to determine potential association with efficacy and safety.

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Sunitinib in Metastatic Transitional Cell Carcinoma of the Urothelium
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Sunitinib This is a phase II trial of Sunitinib in patients with metastatic urothelial carcinoma. Sunitinib will be administered at a dose of 50 mg orally once daily for four consecutive weeks followed by a two-week rest period for the initial population. A second cohort of patients will be enrolled, who will receive 37.5 mg of sunitinib orally, on a continuous dosing schedule. Intra-patient dose reduction may be required depending on the type and severity of individual toxicity encountered. Re-staging imaging studies will be performed after every cycle of treatment during the first 4 cycles and subsequently after every other cycle. Patients may continue on study as long as they are tolerating therapy and in the absence of disease progression.

Drug: sunitinib malate

Outcome Measures

Primary Outcome Measures

1. Overall Objective Response [2 years]

   Response rate as measured by RECIST criteria. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the urothelium, including 1 of the following sites:

• Bladder

• Urethra

• Ureter

• Renal pelvis

• Progressive metastatic disease

• Progressive disease defined as new or progressive lesions on cross-sectional imaging

• Progressed despite prior treatment with cytotoxic chemotherapy

• Measurable disease

• Previously treated disease, as defined by the following:

• Received treatment with 1-4 cytotoxic agents

• Prior therapy must have included ≥ 1 of the following:

• Cisplatin

• Carboplatin

• Paclitaxel

• Docetaxel

• Gemcitabine hydrochloride

• Prior cytotoxic agents in the perioperative or metastatic setting allowed and may have been administered sequentially (e.g., first-line treatment followed by second-line treatment at time of progression) or all as part of a single regimen

• No symptomatic CNS metastases

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Absolute neutrophil count ≥ 1,000/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 8.0 g/dL

• Bilirubin ≤ 1.5 mg/dL (unless Gilbert's disease is present)

• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver function abnormalities are due to underlying malignancy)

• Creatinine ≤ 2.0 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• None of the following within the past 6 months:

• Myocardial infarction

• Severe or unstable angina

• Coronary or peripheral artery bypass graft

• Symptomatic congestive heart failure

• Cerebrovascular accident or transient ischemic attack

• Pulmonary embolism

• No ongoing cardiac dysrhythmias ≥ grade 2

• No prolonged QTc interval on baseline ECG

• No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy

• No preexisting thyroid abnormality (i.e., thyroid function tests that cannot be maintained in the normal range with medication)

• No known HIV- or AIDS-related illness or other active infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy or chemotherapy

• At least 4 weeks since prior major surgery

• No other concurrent investigational drugs

• No concurrent participation in another clinical trial (supportive care trials or non-treatment trials [e.g., quality of life] allowed)

• No concurrent therapeutic doses of warfarin (low-dose warfarin ≤ 2 mg once daily for thromboembolic prophylaxis allowed)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)
• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00397488
• Other Study ID Numbers: 06-081; MSKCC-06081
• First Posted: Nov 9, 2006
• Last Update Posted: Jan 25, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: recurrent bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder; anterior urethral cancer; posterior urethral cancer; recurrent urethral cancer; metastatic transitional cell cancer of the renal pelvis and ureter; recurrent transitional cell cancer of the renal pelvis and ureter; urethral cancer associated with invasive bladder cancer
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urethral Neoplasms; Kidney Neoplasms; Ureteral Neoplasms; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib
Arm/Group Description	Sunitinib in patients with metastatic urothelial carcinoma.
Period Title: Overall Study
STARTED	78
COMPLETED	71
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Sunitinib
Arm/Group Description	Sunitinib in patients with metastatic urothelial carcinoma.
Overall Participants	78
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	39 50%
>=65 years	39 50%
Sex: Female, Male (Count of Participants)
Female	24 30.8%
Male	54 69.2%

Outcome Measures

1. Primary Outcome

Title	Overall Objective Response
Description	Response rate as measured by RECIST criteria. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib
Arm/Group Description	Sunitinib in patients with metastatic urothelial carcinoma.
Measure Participants	71
Partial Response (PR)	3 3.8%
Stable Disease (SD)	29 37.2%
Progression of Disease (POD)	39 50%

Adverse Events

Arm/Group Title	Sunitinib
Arm/Group Description	Sunitinib in patients with metastatic urothelial carcinoma.
All Cause Mortality
	Sunitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	34/78 (43.6%)
Blood and lymphatic system disorders
Hemoglobin	1/78 (1.3%)	1
Platelets	1/78 (1.3%)	1
Cardiac disorders
Cardiac ischemia/infarction	1/78 (1.3%)	1
Hypertension	1/78 (1.3%)	1
Gastrointestinal disorders
Constipation	1/78 (1.3%)	1
Distension/bloating, abdominal	1/78 (1.3%)	1
Fistula, GI- Small bowel	1/78 (1.3%)	1
Nausea	1/78 (1.3%)	1
Small intestinal obstruction	2/78 (2.6%)	2
Abdominal pain	5/78 (6.4%)	5
General disorders
Death not associated with CTCAE term- Death NOS	4/78 (5.1%)	4
Death not associated with CTCAE term-Disease progression	2/78 (2.6%)	2
Dehydration	2/78 (2.6%)	2
Extremity-lower (gait/walking)	1/78 (1.3%)	1
Fatigue (asthenia, lethargy, malaise)	2/78 (2.6%)	2
Fever (in the absence of neutropenia)	1/78 (1.3%)	1
Sepsis	1/78 (1.3%)	1
Pneumonia	1/78 (1.3%)	1
Pain - Back	3/78 (3.8%)	3
Pain - Bone	1/78 (1.3%)	1
Pain - Extremity-limb	2/78 (2.6%)	2
Pain - Head/headache	2/78 (2.6%)	2
Pain - Pelvis	1/78 (1.3%)	1
Infections and infestations
Infection	4/78 (5.1%)	4
Metabolism and nutrition disorders
Creatinine	1/78 (1.3%)	1
Nervous system disorders
Memory impairment	1/78 (1.3%)	1
Renal and urinary disorders
Bladder infection	2/78 (2.6%)	2
Renal failure	2/78 (2.6%)	2
Urinary retention	2/78 (2.6%)	2
Respiratory, thoracic and mediastinal disorders
Thrombosis/thrombus/embolism	2/78 (2.6%)	2
Other (Not Including Serious) Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	67/78 (85.9%)
Blood and lymphatic system disorders
ALT, SGPT	5/78 (6.4%)	5
AST, SGOT	6/78 (7.7%)	6
Hemoglobin	28/78 (35.9%)	28
Leukocytes (total WBC)	29/78 (37.2%)	29
Lymphopenia	19/78 (24.4%)	19
Neutrophils/granulocytes (ANC/AGC)	20/78 (25.6%)	20
Platelets	20/78 (25.6%)	20
Partial thromboplastin time (PTT)	5/78 (6.4%)	5
Cardiac disorders
Hypertension	6/78 (7.7%)	6
Gastrointestinal disorders
Diarrhea	4/78 (5.1%)	4
Heartburn/dyspepsia	5/78 (6.4%)	5
Nausea	7/78 (9%)	7
General disorders
Anorexia	4/78 (5.1%)	4
Fatigue (asthenia, lethargy, malaise)	28/78 (35.9%)	28
Weight loss	4/78 (5.1%)	4
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	6/78 (7.7%)	6
Alkaline phosphatase	8/78 (10.3%)	8
Creatinine	13/78 (16.7%)	13
Glucose, high (hyperglycemia)	18/78 (23.1%)	18
Phosphate, low (hypophosphatemia)	7/78 (9%)	7
Potassium, high (hyperkalemia)	5/78 (6.4%)	5
Sodium, low (hyponatremia)	5/78 (6.4%)	5
Renal and urinary disorders
Hemorrhage, Urinary NOS	5/78 (6.4%)	5
Skin and subcutaneous tissue disorders
Rash: hand-foot skin reaction	13/78 (16.7%)	13

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.