Sunitinib Malate in Treating Patients With Recurrent Transitional Cell Bladder Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01118351
First received: May 5, 2010
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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

PURPOSE: This phase II trial is studying how well sunitinib malate works in treating patients with recurrent transitional cell bladder cancer.


Condition Intervention Phase
Recurrent Bladder Cancer
Transitional Cell Carcinoma of the Bladder
Drug: sunitinib malate
Other: immunohistochemistry staining method
Other: TdT-mediated dUTP nick end labeling assay
Other: light microscopy
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Single Arm, Open Label, Single Institution Study of Continuous Sunitinib (Sutent) in Patients With High-Risk (BCG-Refractory) Superficial Transitional Cell Carcinoma (TCC) of the Bladder

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Complete response rate [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
    Negative cystoscopy with negative biopsy and no evidence of cancer on urine cytology 12 months after treatment with sunitinib.


Secondary Outcome Measures:
  • Recurrence-free survival [ Time Frame: at 12 months after completion of treatment ] [ Designated as safety issue: No ]
    Time from registration to the first documentation of recurrence or death due to any cause. Patients last known to be alive and not to have recurred are censored at the last day of contact.

  • Progression-free survival [ Time Frame: at 12 months after completion of treatment ] [ Designated as safety issue: No ]
    From time of registration to time of first documentation of progression (appearance of new lesions, or death due to any cause). Patients last known to be alive and not to have progressed are censored at the last day of contact.

  • Overall survival [ Time Frame: at 12 months after completion of treatment ] [ Designated as safety issue: No ]
    From date of registration to date of death due to any cause.

  • Angiogenesis [ Time Frame: at 12 months after completion of treatment ] [ Designated as safety issue: No ]
    The secondary outcome measure of response for the correlative studies will be the degree of apoptosis and the overexpression or not of known angiogenic markers (i.e. VEGF-R2, PDGF-R) an comparison by IHC analysis within bladder tumor tissue from the TURBT biopsy specimens with the post sunitinib (Sutent®) treatment TURBT specimens.

  • Immune response [ Time Frame: at 12 months after completion of treatment ] [ Designated as safety issue: No ]
    The secondary outcome measure of response for the correlative studies will be the degree of apoptosis and the overexpression or not of known angiogenic markers (i.e. VEGF-R2, PDGF-R) an comparison by IHC analysis within bladder tumor tissue from the TURBT biopsy specimens with the post sunitinib (Sutent®) treatment TURBT specimens.

  • Toxicity assessed, graded, and tabulated using CTCAE version 3.0 [ Time Frame: D28 of each cycle and at the end of study visit ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: October 2008
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Drug: sunitinib malate
Given orally
Other Names:
  • SU011248
  • SU11248
  • sunitinib
  • Sutent
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Other: TdT-mediated dUTP nick end labeling assay
Correlative studies
Other Name: TUNEL assay
Other: light microscopy
Correlative studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the clinical efficacy of oral sunitinib (Sutent) given continuously for a maximum of 12 weeks, with respect to complete response rates at 12 months after completion of treatment in patients with high-risk superficial bladder cancer who have failed previous intravesical BCG.

SECONDARY OBJECTIVES:

I. To assess the impact of sunitinib treatment in recurrence-free survival, progression-free survival, and overall survival in patients with high-risk superficial TCC of the bladder who have failed previous intravesical BCG.

II. To evaluate the safety and tolerability of sunitinib (Sutent) administered in patients with high-risk superficial TCC of the bladder who have failed previous intravesical BCG.

TERTIARY OBJECTIVES:

I. To assess pre-treatment tissue baseline angiogenic markers and to evaluate the magnitude of the difference among these variables with post-treatment tumor tissue after treatment with sunitinib (Sutent).

II. To evaluate the effects of Sunitinib (Sutent) on immunosuppressive regulatory T cells (Tregs).

III. To determine the presence of circulating tumor cells in superficial BCG-refractory TCC patients.

OUTLINE:

Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  • Patients must have clinically and histologically proven, recurrent superficial transitional cell carcinoma of the bladder after treatment with BCG therapy
  • Patients could have received previous any INTRAVESICAL therapy including BCG and/or IFN and/or chemotherapy up to 3 years prior to registration
  • Patients biopsy specimen should be available for review
  • ECOG PS 0-1 (Karnofsky greater than 70%)
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8.5 g/dl
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) =< 3.5 X institutional upper limit of normal
  • Alkaline phosphatase =< 2.5 ULN ( =< 10 x ULN in presence of bone metastasis)
  • Serum calcium of =< 12 mg/dl
  • Creatinine =< 1.5 X institutional upper limit of normal
  • INR =< 1.5, except for subjects receiving warfarin therapy
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of Sunitinib (Sutent) will be determined following review of their case by the Principal Investigator
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; sexually active patients must continue to use contraception for three months after completion of study therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • All patients must be informed of the investigational nature of this study and must provide written informed consent in accordance with institutional and federal guidelines

Exclusion

  • Prior systemic chemotherapy for bladder cancer; all other systemic chemotherapy must have been completed at least 3 years prior to enrollment
  • Prior treatment with any other anti-angiogenic therapy (including immunomodulatory agents such as thalidomide and lenalidomide, and anti-VEGF therapy with agents such as bevacizumab (Bevacizumab Avastin, Sunitinib (Sutent) and Sorafenib (Nexavar)
  • Prior major surgery (not TURBT/Cystoscopy), radiation therapy, or systemic therapy within 4 weeks of starting the study treatment
  • NCI CTCAE grade 3 hemorrhage within 4 weeks of starting study treatment
  • 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 grade >= 2, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females (Atrial Fibrillation is allowed provided patients are rated controlled)
  • Hypertension that cannot be controlled by medications
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) - related illness or infectious hepatitis type A, B or C
  • Disease-free of prior malignancies for >= 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix
  • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment
  • Pregnancy or breastfeeding (Female patients must be surgically sterile or postmenopausal, or must agree to use effective contraception during the period of therapy; all female patients with reproductive potential must have a negative pregnancy test [serum or urine] prior to enrollment)
  • Male patients must be surgically sterile 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01118351

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
CCF-Fairview Hospital
Cleveland, Ohio, United States, 44111
Sponsors and Collaborators
Case Comprehensive Cancer Center
Pfizer
Investigators
Principal Investigator: Jorge Garcia, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01118351     History of Changes
Other Study ID Numbers: CASE3808, NCI-2010-01137, CASE 3808-CC530
Study First Received: May 5, 2010
Last Updated: January 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 23, 2014