search
Back to results

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

Primary Purpose

Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
sorafenib tosylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Princess Margaret Hospital Phase 2 Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (sorafenib tosylate)

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Paricipants With Tumour Response Defined as Partial or Complete Response Per the RECIST 1.0 Criteria
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

Secondary Outcome Measures

Number of Participants With Stable Disease for More Than 3 Months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time to Progression
Progression is defined using the Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.0) as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in non-target lesions, or the appearance of new lesions.
Progression-free Survival
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 of Common Grade 3 Adverse Events
Will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.

Full Information

First Posted
June 2, 2005
Last Updated
July 26, 2018
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00112671
Brief Title
Sorafenib in Treating Patients With Advanced or Metastatic Cancer of the Urinary Tract
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)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (sorafenib tosylate)
Arm Type
Experimental
Arm Description
Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
sorafenib tosylate
Other Intervention Name(s)
BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN
Intervention Description
Given orally 400mg orally twice daily
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Number of Paricipants With Tumour Response Defined as Partial or Complete Response Per the RECIST 1.0 Criteria
Description
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Number of Participants With Stable Disease for More Than 3 Months
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame
From the start of the treatment until the criteria for progression are met, up to 5 years
Title
Time to Progression
Description
Progression is defined using the Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.0) as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in non-target lesions, or the appearance of new lesions.
Time Frame
Up to 5 years
Title
Progression-free Survival
Description
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.
Time Frame
From start of treatment to progression or death, assessed up to 1 year
Title
Frequency of Common Grade 3 Adverse Events
Description
Will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Srikala Sridhar
Organizational Affiliation
Princess Margaret Hospital Phase 2 Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Hospital Phase 2 Consortium
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs