Sunitinib Malate in Treating Patients With Locally Recurrent, Locally Advanced, Unresectable, or Metastatic Urinary Tract Cancer

Sponsor

Hospital del Mar (Other)

Overall Status

Unknown status

CT.gov ID

NCT01118039

Collaborator

(none)

Enrollment

Locations

10.3

Patients Per Site

Study Details

Study Description

Brief Summary

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

PURPOSE: This phase II trial is studying the side effects of giving sunitinib malate and to see how well it works in treating patients with locally recurrent, locally advanced, unresectable, or metastatic urinary tract cancer.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral Cancer	Drug: sunitinib malate Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: pharmacological study Procedure: quality-of-life assessment	Phase 2

Detailed Description

OBJECTIVES:

Primary

To determine the time to disease progression (defined as the time from diagnosis of metastatic urothelial carcinoma until first confirmed progression of the disease) in patients with locally recurrent, locally advanced, unresectable, or metastatic urothelial cancer treated with sunitinib malate and ineligible for cisplatin-based chemotherapy.
To determine the safety of this drug in these patients.

Secondary

To determine the progression-free survival of patients treated with this drug.
To determine the overall response rate in patients treated with this drug.
To determine the overall survival of patients treated with this drug.
To determine the time to treatment failure in patients treated with this drug.
To determine the pharmacodynamic profile of this drug in pre- and post-treatment serum and tumor tissue (i.e., IL8, VEGF, MMP9, bFGF, p27, Ki-67, and apoptosis [H/E]) at week 6, and if possible, at time of progression.
To determine the quality of life of patients treated with this drug using the QLQ-C30 version 3 questionnaire.

OUTLINE: This is a multicenter study.

Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life questionnaire (EORTC QLQ-C30) before, during, and at the end of study treatment.

Serum and tumor tissue samples are collected at baseline and after study treatment for pharmacodynamic studies. Samples are analyzed for markers (i.e., IL8, VEGF, MMP9, bFGF, p27, Ki-67, and apoptosis [H/E]) via immunohistochemistry.

After completion of study treatment, patients are followed for 28 days and then every 2 months for up to 3 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

41 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study Assessing SU-011248 in Previously Untreated Patients With Advanced Urothelial Cancer Ineligible for Cisplatin-Based Chemotherapy

Study Start Date :

Jul 1, 2006

Anticipated Primary Completion Date :

Dec 1, 2010

Outcome Measures

Primary Outcome Measures

Time to disease progression []
Safety []

Secondary Outcome Measures

Progression-free survival []
Overall response rate []
Overall survival []
Time to treatment failure []
Pharmacodynamic profile []
Quality of life []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed transitional cell carcinoma of the urinary tract meeting ≥ 1 of the following criteria:
Unresectable, locally recurrent disease
Locally recurrent disease must not be amenable to resection or radiotherapy with curative intent
Locally advanced or metastatic disease
No prior chemotherapy for advanced disease
Ineligible (unfit) for cisplatin-based chemotherapy due to creatinine clearance < 60 mL/min but > 30 mL/min
Measurable or nonmeasurable disease according to RECIST criteria
Measurable lesions that have been previously irradiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy

PATIENT CHARACTERISTICS:

See Disease Characteristics
ECOG performance status 0-1
Life expectancy > 12 weeks
Absolute neutrophil count ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Hemoglobin ≥ 9.0 g/dL
Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
Serum creatinine ≤ 1.5 times ULN
AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver function abnormalities are due to underlying malignancy)
Serum albumin ≥ 3.0 g/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during study therapy
No diagnosis of a second malignancy within the past 3 years except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
None of the following within the past 12 months:
Myocardial infarction
Severe/unstable angina
Coronary/peripheral artery bypass graft
Congestive heart failure
Cerebrovascular accident, including transient ischemic attack
Pulmonary embolus
No ongoing cardiac dysrhythmias (NCI CTCAE grade ≥ 2), atrial fibrillation of any grade, or QTc interval > 450 msec (males) or > 470 msec (females)
No hypertension that cannot be controlled by medications (> 150/100 mm Hg despite optimal medical therapy)
No known HIV infection
No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which would make the patient inappropriate for entry into this study

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from all acute toxic effects of prior therapy or surgical procedures to grade ≤ 1 (except alopecia)
At least 3 weeks since prior major surgery, radiotherapy, or systemic therapy (except palliative radiotherapy to non-target metastatic lesions)
Not enrolled in a dialysis program or anticipating a need for dialysis
No prior chemotherapy regimen or biological treatment for locally advanced or metastatic transitional cell carcinoma of the urinary tract
No prior treatment on another sunitinib malate clinical trial
No prior tyrosine kinase inhibitors, VEGF inhibitors, or other angiogenic inhibitors
No prior high-dose chemotherapy requiring hematopoietic stem cell rescue
No prior radiotherapy to > 25% of the bone marrow
No concurrent treatment on another clinical trial
No concurrent treatment with therapeutic doses of acenocoumarol

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital Del Mar	Barcelona	Spain	08003
2	Hospital de la Santa Cruz i Sant Pau	Barcelona	Spain	08025
3	Hospital Universitario San Carlos	Madrid	Spain	28040
4	Hospital Universitario 12 de Octubre	Madrid	Spain	28041