- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00749892
Erlotinib Hydrochloride in Treating Participants With Muscle Invasive or Recurrent Urothelial Cancer
A Phase II Exploratory Study of Pre-Operative Treatment With Erlotinib (Tarceva) in Muscle Invasive or Recurrent Transitional Cell Carcinoma Requiring Cystectomy
Study Overview
Status
Conditions
- Recurrent Bladder Urothelial Carcinoma
- Recurrent Renal Pelvis Urothelial Carcinoma
- Recurrent Ureter Urothelial Carcinoma
- Recurrent Urethral Urothelial Carcinoma
- Stage III Renal Pelvis Cancer AJCC v8
- Stage III Ureter Cancer AJCC v8
- Stage III Urethral Cancer AJCC v8
- Stage 0a Bladder Cancer AJCC v8
- Stage 0is Bladder Cancer AJCC v8
- Stage IIIA Bladder Cancer AJCC v8
- Stage II Bladder Cancer AJCC v8
- Stage 0a Renal Pelvis Cancer AJCC v8
- Stage 0a Ureter Cancer AJCC v8
- Stage 0is Renal Pelvis Cancer AJCC v8
- Stage 0is Ureter Cancer AJCC v8
- Stage II Renal Pelvis Cancer AJCC v8
- Stage II Ureter Cancer AJCC v8
- Stage II Urethral Cancer AJCC v8
- Stage 0a Urethral Cancer AJCC v8
- Stage 0is Urethral Cancer AJCC v8
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the response rate (ie: pT0 rate) of patients with urothelial cancer treated with erlotinib prior to cystectomy.
SECONDARY OBJECTIVES:
I. 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.
V. 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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Texas
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Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (erlotinib hydrochloride)
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.
|
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response Rate
Time Frame: Determined at the time of surgery or cystectomy
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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.
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Determined at the time of surgery or cystectomy
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Estimated 4-Year Disease-Free Survival
Time Frame: 4 years
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4 years
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Neoplasms, Glandular and Epithelial
- Urinary Bladder Diseases
- Disease Attributes
- Ureteral Diseases
- Urethral Diseases
- Kidney Neoplasms
- Carcinoma
- Recurrence
- Urinary Bladder Neoplasms
- Pelvic Neoplasms
- Carcinoma, Transitional Cell
- Ureteral Neoplasms
- Urethral Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Erlotinib Hydrochloride
Other Study ID Numbers
- 2007-0704 (OTHER: M D Anderson Cancer Center)
- P30CA016672 (U.S. NIH Grant/Contract)
- NCI-2018-01833 (REGISTRY: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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