Recurrent Bladder Urothelial CarcinomaPhase 2NCT00749892
Erlotinib Hydrochloride in Treating Participants With Muscle Invasive or Recurrent Urothelial Cancer
A Phase 2 study testing Erlotinib Hydrochloride in people with Recurrent Bladder Urothelial Carcinoma and Recurrent Renal Pelvis Urothelial Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well erlotinib hydrochloride works in Treating participants with muscle invasive urothelial cancer or urothelial cancer that has come back. Drugs used in chemotherapy, such as erlotinib hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma
- What is being tested?
- Erlotinib Hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jun 2008to 26 Nov 2019
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologic proof of urothelial cancer. This includes bladder cancer, in addition to other tumors of the urothelial lining including renal pelvis, ureteral, and urethral cancer. This group may include any patient requiring cystectomy, including patients with recurrent or extensive superficial disease (cTa-T1N0M0), CIS (carcinoma in situ), or muscle invasive disease (cT2-3aN0M0), whose tumor could not be completely removed at transurethral resection
- Patients with the following high-risk features: Micropapillary features (more than focal on pathology); Small cell carcinoma; 3-dimensional (D) mass on exam under anesthesia (EUA); Lymphovascular invasion; Hydronephrosis (unless in the opinion of the treating physician, this is not due to tumor); High grade (grade 3) tumors of the ureter, renal pelvis, or urethra, or tumors in these areas with radiographic abnormality large enough to recognize as an abnormal mass by computed tomography (CT) or magnetic resonance imaging (MRI) imaging; Direct invasion of the prostatic stroma or the vaginal wall (ie: cT4a disease) should be offered neoadjuvant cytoreductive chemotherapy (ie: cisplatin-based). Patients refusing or who are not considered candidates for cytoreductive chemotherapy may be considered eligible. Dr. Siefker-Radtke will be the final arbiter in determining eligibility for the trial
- Please note that the presence of variant histologic subtypes is acceptable, except in the case for small cell variant which is traditionally treated with cytoreductive chemotherapy. Patients with small cell who refuse recommended cytoreductive chemotherapy may still be considered eligible
- Patients must have an evaluation in the department of urology, and be deemed an acceptable surgical candidate
- Patients must NOT have clinical evidence of metastatic disease by either CT or MRI of the abdomen and pelvis, and chest x-ray. In the absence of a bone scan, patients should be free of bone pain and have an alkaline phosphatase < 1.5 x upper limit of normal (ULN) of the upper limit of normal, or a normal bone fraction of alkaline phosphatase. If these features are present, patients should have a bone scan and this should be interpreted as showing no evidence of metastatic disease in order to be eligible
- Patients, 18 years and older, must either be not of child bearing potential or have a negative pregnancy test within 2 weeks of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
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- Absolute neutrophil count (ANC) >= 1,000/ul
- Platelets >= 75,000/microliters
- Creatinine =< 2.0 x institutional upper limit of normal (ULN), or a creatinine clearance of > 30 ml/min as calculated by Cockroft-Gault or by 24-hour urine collection
- Bilirubin =< 2.5 x ULN
- Aspartate aminotransferase (AST) =< 5.0 x ULN
- Zubrod performance status (PS) =< 2
- Patients with second malignancies are eligible provided that the expected outcome from the second cancer is such that this will not interfere in the delivery of this therapy, or in doing cystectomy, and provided that the expectation of survival from any prior malignancy is reliably > 4 years
Who cannot join
- Acute hepatitis or known human immunodeficiency virus (HIV)
- Active or uncontrolled infection
- Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction =< 40%
- Prior therapy specifically and directly targeting the EGFR pathway
- Patients with interstitial lung disease
- Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s)
- Patients with metastatic or surgically unresectable disease are not eligible for this study. In addition, patients who do not agree to surgery are not eligible for this trial
- Patients who have received prior systemic chemotherapy or radiation therapy for urothelial cancer are not eligible. Any prior intravesical chemotherapy is allowed
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Exploratory Study of Pre-Operative Treatment With Erlotinib (Tarceva) in Muscle Invasive or Recurrent Transitional Cell Carcinoma Requiring Cystectomy
This phase II trial studies how well erlotinib hydrochloride works in Treating participants with muscle invasive urothelial cancer or urothelial cancer that has come back. Drugs used in chemotherapy, such as erlotinib hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the response rate (ie: pT0 rate) of patients with urothelial cancer treated with erlotinib prior to cystectomy.
SECONDARY OBJECTIVES:
- To estimate the 4-year disease-free survival of patients with urothelial cancer treated with erlotinib prior to cystectomy.
II. To measure epithelial-mesenchymal transition (EMT) markers (E-cadherin, HER4, PDGFR-beta, vimentin, fibronectin) in pre- and post-treatment biopsies and correlate expression patterns with the biological responses measured below.
III. To quantify target inhibition, antiproliferation (KI-67), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) in biopsies obtained from patients before, during, and after therapy.
IV. Interrogate membrane (phosphorylated EGFR) and downstream receptor signaling pathways (ERKs, AKT/mTOR, GSK-3beta) to provide further insight into whether or not a given tumor displays a biological response.
- To correlate the changes in Ki-67 expression with changes in angiogenesis and angiogenesis related gene expression utilizing fluorescent tissue staining techniques that we have developed in the laboratory (such as two-color TUNEL, phosphor-receptor, and microvessel density.) VI. To profile messenger ribonucleic acid (mRNA) expression in pre- and post-treatment biopsies using Affymetrix arrays and correlate the changes observed with EMT, growth arrest, and apoptosis.
VII. To quantify EGFR copy number and correlate with changes observed with EMT, growth arrest, and apoptosis.
OUTLINE:
Participants receive erlotinib hydrochloride orally (PO) once daily (QD) for 3-5 weeks in the absence of disease progression or unacceptable toxicity. Within 24 hours of the last dose, participants undergo cystectomy.
After completion of study treatment, participants are followed up every 6 months for 1 year, then annually for 4 years.
- Conditions
- Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0a Renal Pelvis Cancer AJCC v8
- Being tested
- Erlotinib Hydrochloride
- Medical subject headings
- Urinary Bladder Neoplasms, Ureteral Neoplasms, Urethral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erlotinib HydrochlorideDrug
Also called Cp-358,774, OSI-774, Tarceva
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (erlotinib hydrochloride) | Experimental | Participants receive erlotinib hydrochloride PO QD for 3-5 weeks in the absence of disease progression or unacceptable toxicity. Within 24 hours of the last dose, participants undergo cystectomy. Receives: Drug: Erlotinib Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
The response rate is the number of patients with urothelial cancer treated with erlotinib prior to cystectomy. The response is defined as the absence of residual cancer in the surgical removed tissue (i.e., pT0). A responder is defined as a participant with the pathological stage of pT0 meaning that there is no evidence of disease.
Measured: Determined at the time of surgery or cystectomy
Secondary outcomes (1)
Estimated 4-Year Disease-Free Survival
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2008 (estimated)
- Study start10 Jun 2008
- Primary completion30 Jun 2019
- Study completion26 Nov 2019
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 Recurrent Bladder Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Arlene Siefker-Radtke, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00749892
- Sponsor's protocol ID
- 2007-0704
- Other IDs
- NCI-2018-01833, 2007-0704, P30CA016672
- Status last verified
- Aug 2020
- First submitted
- 5 Sep 2008
- Last updated
- 10 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Exploratory Study of Pre-Operative Treatment With Erlotinib (Tarceva) in Muscle Invasive or Recurrent Transitional Cell Carcinoma Requiring Cystectomy
- ClinicalTrials.gov ID
- NCT00749892
- Acronym / sponsor ID
- 2007-0704
- Conditions
- Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0a Renal Pelvis Cancer AJCC v8
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Jun 2008 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 26 Nov 2019 (actual)
- First posted
- 9 Sep 2008 (estimated)
- Results
- Posted 10 Sep 2020
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 studies how well erlotinib hydrochloride works in Treating participants with muscle invasive urothelial cancer or urothelial cancer that has come back. Drugs used in chemotherapy, such as erlotinib hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the response rate (ie: pT0 rate) of patients with urothelial cancer treated with erlotinib prior to cystectomy.
SECONDARY OBJECTIVES:
- To estimate the 4-year disease-free survival of patients with urothelial cancer treated with erlotinib prior to cystectomy.
II. To measure epithelial-mesenchymal transition (EMT) markers (E-cadherin, HER4, PDGFR-beta, vimentin, fibronectin) in pre- and post-treatment biopsies and correlate expression patterns with the biological responses measured below.
III. To quantify target inhibition, antiproliferation (KI-67), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) in biopsies obtained from patients before, during, and after therapy.
IV. Interrogate membrane (phosphorylated EGFR) and downstream receptor signaling pathways (ERKs, AKT/mTOR, GSK-3beta) to provide further insight into whether or not a given tumor displays a biological response.
- To correlate the changes in Ki-67 expression with changes in angiogenesis and angiogenesis related gene expression utilizing fluorescent tissue staining techniques that we have developed in the laboratory (such as two-color TUNEL, phosphor-receptor, and microvessel density.) VI. To profile messenger ribonucleic acid (mRNA) expression in pre- and post-treatment biopsies using Affymetrix arrays and correlate the changes observed with EMT, growth arrest, and apoptosis.
VII. To quantify EGFR copy number and correlate with changes observed with EMT, growth arrest, and apoptosis.
OUTLINE:
Participants receive erlotinib hydrochloride orally (PO) once daily (QD) for 3-5 weeks in the absence of disease progression or unacceptable toxicity. Within 24 hours of the last dose, participants undergo cystectomy.
After completion of study treatment, participants are followed up every 6 months for 1 year, then annually for 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (erlotinib hydrochloride) | Experimental | Drug: Erlotinib HydrochlorideParticipants receive erlotinib hydrochloride PO QD for 3-5 weeks in the absence of disease progression or unacceptable toxicity. Within 24 hours of the last dose, participants undergo cystectomy. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologic proof of urothelial cancer. This includes bladder cancer, in addition to other tumors of the urothelial lining including renal pelvis, ureteral, and urethral cancer. This group may include any patient requiring cystectomy, including patients with recurrent or extensive superficial disease (cTa-T1N0M0), CIS (carcinoma in situ), or muscle invasive disease (cT2-3aN0M0), whose tumor could not be completely removed at transurethral resection
- Patients with the following high-risk features: Micropapillary features (more than focal on pathology); Small cell carcinoma; 3-dimensional (D) mass on exam under anesthesia (EUA); Lymphovascular invasion; Hydronephrosis (unless in the opinion of the treating physician, this is not due to tumor); High grade (grade 3) tumors of the ureter, renal pelvis, or urethra, or tumors in these areas with radiographic abnormality large enough to recognize as an abnormal mass by computed tomography (CT) or magnetic resonance imaging (MRI) imaging; Direct invasion of the prostatic stroma or the vaginal wall (ie: cT4a disease) should be offered neoadjuvant cytoreductive chemotherapy (ie: cisplatin-based). Patients refusing or who are not considered candidates for cytoreductive chemotherapy may be considered eligible. Dr. Siefker-Radtke will be the final arbiter in determining eligibility for the trial
- Please note that the presence of variant histologic subtypes is acceptable, except in the case for small cell variant which is traditionally treated with cytoreductive chemotherapy. Patients with small cell who refuse recommended cytoreductive chemotherapy may still be considered eligible
- Patients must have an evaluation in the department of urology, and be deemed an acceptable surgical candidate
- Patients must NOT have clinical evidence of metastatic disease by either CT or MRI of the abdomen and pelvis, and chest x-ray. In the absence of a bone scan, patients should be free of bone pain and have an alkaline phosphatase < 1.5 x upper limit of normal (ULN) of the upper limit of normal, or a normal bone fraction of alkaline phosphatase. If these features are present, patients should have a bone scan and this should be interpreted as showing no evidence of metastatic disease in order to be eligible
Key exclusion criteria (8 listed)
- Acute hepatitis or known human immunodeficiency virus (HIV)
- Active or uncontrolled infection
- Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction =< 40%
- Prior therapy specifically and directly targeting the EGFR pathway
- Patients with interstitial lung disease
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 |
|---|---|---|
| Erlotinib HydrochlorideAlso: Cp-358,774, OSI-774, TarcevaGiven PO | Drug | Treatment (erlotinib hydrochloride) |
Primary outcome
Response Rate
Time frame: Determined at the time of surgery or cystectomy
The response rate is the number of patients with urothelial cancer treated with erlotinib prior to cystectomy. The response is defined as the absence of residual cancer in the surgical removed tissue (i.e., pT0). A responder is defined as a participant with the pathological stage of pT0 meaning that there is no evidence of disease.
1 secondary outcome
Estimated 4-Year Disease-Free Survival
Time frame: 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Arlene Siefker-Radtke principal investigator
M.D. Anderson Cancer Center
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 Erlotinib Hydrochloride in people with Recurrent Bladder Urothelial Carcinoma and Recurrent Renal Pelvis Urothelial Carcinoma, run by M.D. Anderson Cancer Center 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 13 inclusion and 8 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: finished, as of the sponsor's last update on 10 Sep 2020. 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 10 Sep 2020). 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?
Response Rate (time frame: Determined at the time of surgery or cystectomy). 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 10 Sep 2020.