Adenocarcinoma of the BladderPhase 2NCT00112905
Sorafenib in Treating Patients With Regional or Metastatic Cancer of the Urothelium
A Phase 2 study testing sorafenib tosylate and laboratory biomarker analysis in people with Adenocarcinoma of the Bladder and Distal Urethral Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well sorafenib works in treating patients with progressive regional or metastatic cancer of the urothelium. 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Bladder, Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
- What is being tested?
- sorafenib tosylate and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2005to Mar 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed transitional cell carcinoma or mixed histologies containing a component of transitional cell carcinoma of the urothelium (renal pelvis, ureter, bladder, urethra) with manifestations of progressing regional or metastatic cancer; or (2) Nontransitional cell histologies include patients with adenocarcinoma or squamous cell carcinomas representing greater than 90% of specimen; patients with small cell carcinoma, soft tissue sarcomas, or carcinosarcomas are excluded
- Measurable disease, as defined in the RECIST criteria; all sites of disease must be evaluated within 4 weeks prior to registration
- Patients must have progressed on one and only one prior systemic chemotherapy for metastatic disease; prior chemotherapy administered in the adjuvant or neoadjuvant setting is permitted (i.e. does not count as 1 prior regimen) provided that it was completed greater than 12 months prior to the start of the first chemotherapy regimen administered in the metastatic setting
- Patients must not have had prior systemic biologic response modifier therapy; patients must not have had chemotherapy, hormonal or biologic therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or have recovered from adverse events due to agents administered more than 4 weeks earlier
- Prior radiotherapy is allowed; patients must be >= 2 weeks post-radiotherapy at time of registration; a previously irradiated lesion can only be used as a marker lesion if there is unequivocal evidence of progression demonstrated on serial imaging studies; patients must have recovered from all toxicities associated with prior radiotherapy
- Patients must be >= 4 weeks post-major surgery at time of registration; patients must have recovered from all toxicities associated with prior surgery
Show all 22Show fewer
- ECOG performance status of 0 or 1
- No history of severe cardiovascular disease (AHA Class III or IV), uncontrolled CHF, uncontrolled hypertension, or ventricular dysrhythmias
- Patients with previously resected and irradiated CNS metastases with evidence of stable disease are eligible
- Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been disease free for >= 5 years; curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix must have been treated with curative intent; patients with clinically unsuspected organ confined prostate cancer found at the time of cystoprostatectomy are eligible
- Creatinine < 1.5 mg/dL
- Granulocytes >= 1500/mm^3
- Platelets >= 100,000/mm^3
- AST =< 2.5 x institutional upper limit of normal
- Bilirubin < 1.5 mg/dl
- No active unresolved infection requiring parenteral antibiotics < 7 days prior to study entry
- Patients must not have a swallowing dysfunction which would prevent the ingesting of pills
- Patients must not have any evidence of bleeding diathesis
- Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e. 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, and phenobarbital), rifampin, or St. John's Wort
- Women of childbearing potential must not be pregnant (as proven by a negative pregnancy test within 14 days prior to registration) or breast feeding because the effects of this treatment on the fetus and breast-fed infants is unknown
- Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Eastern Cooperative Oncology Group
Boston, Massachusetts, 02215
About this study
Official title: Phase II Trial of Sorafenib (BAY 43-9006) (IND 69896; NSC 724772) in Patients With Advanced Urothelial Cancer
This phase II trial is studying how well sorafenib works in treating patients with progressive regional or metastatic cancer of the urothelium. 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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the 4-month progression-free survival rate, response rate and toxicity of BAY 43-9006 in patients with progressing regional or metastatic transitional cell carcinoma (or mixed histologies containing a component of TCC) of the urothelium who have progressed on one and only one prior systemic chemotherapy regimen for metastatic disease.
SECONDARY OBJECTIVES:
- To determine the time to disease progression and overall survival with BAY 43-9006.
II. To evaluate the frequency of polymorphisms in drug metabolizing enzymes and to correlate these polymorphisms with variations in BAY 43-9006 pharmacokinetics.
III. To evaluate the frequency of raf kinase mutations in tumor specimens and correlate these with response rate.
IV. To evaluate serum VEGF levels as potential markers of angiogenesis inhibition by BAY 43-9006.
- To evaluate markers of apoptosis and kinase inhibition in peripheral blood mononuclear cells as potential biomarkers of BAY 43-9006 activity.
VI. To determine if there are proteins differentially translated from the genome in patients who respond to treatment with BAY 43-9006 versus patients who do not respond to BAY 43-9006.
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib twice daily on days 1-56. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until 2 years from study entry and then every 6 months until 3 years from study entry.
- Conditions
- Adenocarcinoma of the Bladder, Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
- Being tested
- sorafenib tosylate, laboratory biomarker analysis
- Medical subject headings
- Urinary Bladder Neoplasms, Urethral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenib tosylateDrug
Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar
Given PO
laboratory biomarker analysisOther
Optional correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (sorafenib tosylate) | Experimental | Patients receive oral sorafenib twice daily on days 1-56. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: sorafenib tosylate; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kaplan-Meier Estimate of Progression-free Survival at 4 Months
Survival estimate from the Kaplan-Meier curve of the proportion of patients alive and progression-free at 4 months.
Progression-free survival is defined as the time from registration to progression or death, whichever occurs first.
Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.
Measured: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Secondary outcomes (3)
Progression-free Survival
Time from registration to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.
Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.
Measured: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Overall Survival
Time from registration to death. Patients alive at last follow-up were censored.
Measured: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Best Overall Response by RECIST
This outcome measure reports the best response a patient has ever experienced.
<Target Lesions>
Complete Response (CR):
The disappearance of all target lesions, confirmed by assessments >=4 weeks (wks) later.
Partial Response:
>=30% decrease in the sum of the longest diameters of target lesions from baseline, confirmed by assessments >=4 wks later.
Progressive Disease (PD):
>=20% increase in the sum of the longest diameters of target lesions from the smallest sum longest diameter since baseline, or the appearance of new lesions.
Stable Disease (SD):
Neither response criteria nor progressive disease criteria are met for >=8 wks.
<Nontarget Lesions>
CR:
The disappearance of all nontarget lesions and normalization of tumor marker levels, confirmed by assessments >=4 wks later.
SD:
Persistence of nontarget lesions or maintenance of tumor marker levels above the normal limits for >=8 wks.
PD:
The appearance of new lesions or unequivocal progression of existing lesions.
Measured: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2005 (estimated)
- Study startOct 2005
- Primary completionMar 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenocarcinoma of the BladderStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert Dreicer, Principal investigator, Eastern Cooperative Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00112905
- Sponsor's protocol ID
- NCI-2012-02975
- Other IDs
- NCI-2012-02975, U10CA021115, E1804, E1804
- Status last verified
- Dec 2012
- First submitted
- 2 Jun 2005
- Last updated
- 30 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Sorafenib (BAY 43-9006) (IND 69896; NSC 724772) in Patients With Advanced Urothelial Cancer
- ClinicalTrials.gov ID
- NCT00112905
- Acronym / sponsor ID
- NCI-2012-02975
- Conditions
- Adenocarcinoma of the Bladder, Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 27 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2005
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 3 Jun 2005 (estimated)
- Results
- Posted 4 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well sorafenib works in treating patients with progressive regional or metastatic cancer of the urothelium. 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:
- To evaluate the 4-month progression-free survival rate, response rate and toxicity of BAY 43-9006 in patients with progressing regional or metastatic transitional cell carcinoma (or mixed histologies containing a component of TCC) of the urothelium who have progressed on one and only one prior systemic chemotherapy regimen for metastatic disease.
SECONDARY OBJECTIVES:
- To determine the time to disease progression and overall survival with BAY 43-9006.
II. To evaluate the frequency of polymorphisms in drug metabolizing enzymes and to correlate these polymorphisms with variations in BAY 43-9006 pharmacokinetics.
III. To evaluate the frequency of raf kinase mutations in tumor specimens and correlate these with response rate.
IV. To evaluate serum VEGF levels as potential markers of angiogenesis inhibition by BAY 43-9006.
- To evaluate markers of apoptosis and kinase inhibition in peripheral blood mononuclear cells as potential biomarkers of BAY 43-9006 activity.
VI. To determine if there are proteins differentially translated from the genome in patients who respond to treatment with BAY 43-9006 versus patients who do not respond to BAY 43-9006.
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib twice daily on days 1-56. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until 2 years from study entry and then every 6 months until 3 years from study entry.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (sorafenib tosylate) | Experimental | Drug: sorafenib tosylate, Other: laboratory biomarker analysisPatients receive oral sorafenib twice daily on days 1-56. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histologically confirmed transitional cell carcinoma or mixed histologies containing a component of transitional cell carcinoma of the urothelium (renal pelvis, ureter, bladder, urethra) with manifestations of progressing regional or metastatic cancer; or (2) Nontransitional cell histologies include patients with adenocarcinoma or squamous cell carcinomas representing greater than 90% of specimen; patients with small cell carcinoma, soft tissue sarcomas, or carcinosarcomas are excluded
- Measurable disease, as defined in the RECIST criteria; all sites of disease must be evaluated within 4 weeks prior to registration
- Patients must have progressed on one and only one prior systemic chemotherapy for metastatic disease; prior chemotherapy administered in the adjuvant or neoadjuvant setting is permitted (i.e. does not count as 1 prior regimen) provided that it was completed greater than 12 months prior to the start of the first chemotherapy regimen administered in the metastatic setting
- Patients must not have had prior systemic biologic response modifier therapy; patients must not have had chemotherapy, hormonal or biologic therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or have recovered from adverse events due to agents administered more than 4 weeks earlier
- Prior radiotherapy is allowed; patients must be >= 2 weeks post-radiotherapy at time of registration; a previously irradiated lesion can only be used as a marker lesion if there is unequivocal evidence of progression demonstrated on serial imaging studies; patients must have recovered from all toxicities associated with prior radiotherapy
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sorafenib tosylateAlso: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, NexavarGiven PO | Drug | Treatment (sorafenib tosylate) |
| laboratory biomarker analysisOptional correlative studies | Other | Treatment (sorafenib tosylate) |
Primary outcome
Kaplan-Meier Estimate of Progression-free Survival at 4 Months
Time frame: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Survival estimate from the Kaplan-Meier curve of the proportion of patients alive and progression-free at 4 months. Progression-free survival is defined as the time from registration to progression or death, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.
3 secondary outcomes
Progression-free Survival
Time frame: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Overall Survival
Time frame: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Best Overall Response by RECIST
Time frame: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Dreicer principal investigator
Eastern Cooperative Oncology Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sorafenib tosylate and laboratory biomarker analysis in people with Adenocarcinoma of the Bladder and Distal Urethral Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kaplan-Meier Estimate of Progression-free Survival at 4 Months (time frame: Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2014.