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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00112671
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Months): 61
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	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

Detailed Description

PRIMARY OBJECTIVES:

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

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

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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)
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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 400mg orally twice daily; Other Names: BAY 43-9006 BAY 43-9006 Tosylate Salt BAY 54-9085 Nexavar SFN ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Paricipants With Tumour Response Defined as Partial or Complete Response Per the RECIST 1.0 Criteria [Up to 5 years]

   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

1. Number of Participants With Stable Disease for More Than 3 Months [From the start of the treatment until the criteria for progression are met, up to 5 years]

   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.

2. Time to Progression [Up to 5 years]

   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.

3. Progression-free Survival [From start of treatment to progression or death, assessed up to 1 year]

   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.

4. Frequency of Common Grade 3 Adverse Events [Up to 5 years]

   Will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Princess Margaret Hospital Phase 2 Consortium	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Srikala Sridhar, Princess Margaret Hospital Phase 2 Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00112671
• Other Study ID Numbers: NCI-2012-03095; PHL-036; 7062; N01CM62203
• First Posted: Jun 3, 2005
• Last Update Posted: Jul 27, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Kidney Neoplasms; Ureteral Neoplasms; Recurrence; Sorafenib

Study Results

Participant Flow

Arm/Group Title	Treatment (Sorafenib Tosylate)
Arm/Group 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. sorafenib tosylate: Given orally laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	17
COMPLETED	17
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Sorafenib Tosylate)
Arm/Group 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. sorafenib tosylate: Given orally laboratory biomarker analysis: Correlative studies
Overall Participants	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 47.1%
>=65 years	9 52.9%
Sex: Female, Male (Count of Participants)
Female	3 17.6%
Male	14 82.4%
Region of Enrollment (participants) [Number]
Canada	17 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Sorafenib Tosylate)
Arm/Group 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. sorafenib tosylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Number [participants]	0 0%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Stable disease for more than 3 months

Arm/Group Title	Treatment (Sorafenib Tosylate)
Arm/Group 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. sorafenib tosylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Number [participants]	1 5.9%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Sorafenib Tosylate)
Arm/Group 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. sorafenib tosylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Median (95% Confidence Interval) [months]	1.9

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

3 months progression free survival

Arm/Group Title	Treatment (Sorafenib Tosylate)
Arm/Group 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. sorafenib tosylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	14
Median (95% Confidence Interval) [percentage of participants]	27 158.8%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Sorafenib Tosylate)
Arm/Group 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. sorafenib tosylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Number [common grade 3 events]	3

Adverse Events

Arm/Group Title	Treatment (Sorafenib Tosylate)
Arm/Group 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. sorafenib tosylate: Given orally laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Sorafenib Tosylate)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Sorafenib Tosylate)
	Affected / at Risk (%)	# Events
Total	2/17 (11.8%)
General disorders
Multi-organ failure	1/17 (5.9%)	1
Death NOS	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Sorafenib Tosylate)
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Gastrointestinal disorders
Constipation	11/17 (64.7%)	11
Abdominal pain	11/17 (64.7%)	11
Abdominal pain	4/17 (23.5%)	4
General disorders
Fatigue	16/17 (94.1%)	16
Infections and infestations
bladder infection	3/17 (17.6%)	3
Metabolism and nutrition disorders
Anorexia	12/17 (70.6%)	12
Musculoskeletal and connective tissue disorders
back pain	4/17 (23.5%)	4
Skin and subcutaneous tissue disorders
hand-foot reaction	3/17 (17.6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.