Sorafenib in Treating Patients With Advanced or Metastatic Cancer of the Urinary Tract

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00112671
First received: June 2, 2005
Last updated: May 6, 2013
Last verified: May 2013
  Purpose

This phase II trial is studying how well sorafenib works in treating patients with advanced or metastatic cancer of the urinary tract. Sorafenib 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.


Condition Intervention Phase
Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
Recurrent Bladder Cancer
Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
Stage III Bladder Cancer
Stage IV Bladder Cancer
Transitional Cell Carcinoma of the Bladder
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of BAY 43-9006 in Advanced or Metastatic Urothelial Cancer (Transitional Cell Cancer of the Bladder, Ureter and Renal Pelvis)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Antitumor activity of BAY 43-9006 using objective tumor response rate defined as partial or complete response by the RECIST criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated using figures and plots.


Secondary Outcome Measures:
  • Rate and duration of stable disease [ Time Frame: From the start of the treatment until the criteria for progression are met, up to 5 years ] [ Designated as safety issue: No ]
    Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Time to progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Progression-free survival [ Time Frame: From start of treatment to progression, assessed up to 1 year ] [ Designated as safety issue: No ]
    Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Survival estimates will be computed using the Kaplan-Meier method. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated.

  • Frequency and severity of adverse events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.


Enrollment: 33
Study Start Date: April 2005
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sorafenib tosylate)
Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the efficacy (response rate and stable disease rate) of Bay 439006 given to patients with advanced or metastatic urothelial cancer.

II. To assess the toxicity, time to progression and response duration of Bay 439006 given to patients with advanced or metastatic urothelial cancer.

III. To measure Ras mutational status and EGFR/HER2 on archival specimens. To determine baseline and post-treatment levels of pERK, pAKT, VEGFR2, CD31, Ki-67/MIB-1, and cleaved caspase 3 and to explore the relationship between these correlative endpoints and clinical outcome.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed within 3 weeks and then every 3 months thereafter.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed transitional cell cancer of the bladder, renal pelvis or ureter
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • Patients must not have had any prior systemic therapy for advanced or metastatic disease; prior adjuvant or neoadjuvant chemotherapy is permitted providing it was completed at least 4 weeks prior to study entry; radiation therapy is permitted if completed > 4 weeks prior to trial entry
  • Life expectancy of greater than 3 months
  • ECOG performance status 0 or 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • Creatinine < 1.5 x ULN OR creatinine clearance >= 45 mL/min/1.73 m^2
  • No serious medical conditions such as myocardial infarction within 6 months prior to entry, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, or any other medical conditions that might be aggravated by treatment
  • Patients must have tumor lesions accessible for biopsy for correlative studies and must be willing to undergo tumor biopsy once before and once during experimental therapy; if there is a medical contraindication to biopsy, exception may be granted upon discussion with the Principal Investigator/Chair
  • 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Able to swallow and retain oral medication
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior systemic therapy for advanced or metastatic urothelial carcinoma
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents
  • Patients receiving any other investigational agents, or concurrent anticancer therapy
  • Patients with only non-measurable disease, defined as all other lesions, including small lesions (longest diameter < 20mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions, which include the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound evaluation of neurologic and other adverse events
  • Patients with a history of other active malignancy in the past 5 years (with the exception of adequately treated cervical carcinoma in situ and non melanomatous skin cancers) are excluded
  • Uncontrolled intercurrent illness including, but no limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients must not have any evidence of a bleeding diathesis
  • Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (ie. Low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met
  • Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or Phenobarbital), rifampin or St. John's Wort
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with BAY 43-9006
  • Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006
  • Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112671

Locations
Canada, Ontario
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Srikala Sridhar Princess Margaret Hospital Phase 2 Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112671     History of Changes
Other Study ID Numbers: NCI-2012-03095, PHL-036, 7062, N01CM62203
Study First Received: June 2, 2005
Last Updated: May 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Diseases
Ureteral Diseases
Sorafenib
Niacinamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014