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Erlotinib Hydrochloride in Treating Participants With Muscle Invasive or Recurrent Urothelial Cancer

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ClinicalTrials.gov Identifier: NCT00749892
Recruitment Status : Active, not recruiting
First Posted : September 9, 2008
Last Update Posted : September 17, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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, by stopping them from dividing, or by stopping them from spreading.

Condition or disease Intervention/treatment Phase
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 Stage 0a Ureter Cancer AJCC v8 Stage 0a Urethral Cancer AJCC v8 Stage 0is Bladder Cancer AJCC v8 Stage 0is Renal Pelvis Cancer AJCC v8 Stage 0is Ureter Cancer AJCC v8 Stage 0is Urethral Cancer AJCC v8 Stage II Bladder Cancer AJCC v8 Stage II Renal Pelvis Cancer AJCC v8 Stage II Ureter Cancer AJCC v8 Stage II Urethral Cancer AJCC v8 Stage III Renal Pelvis Cancer AJCC v8 Stage III Ureter Cancer AJCC v8 Stage III Urethral Cancer AJCC v8 Stage IIIA Bladder Cancer AJCC v8 Drug: Erlotinib Hydrochloride Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Exploratory Study of Pre-Operative Treatment With Erlotinib (Tarceva) in Muscle Invasive or Recurrent Transitional Cell Carcinoma Requiring Cystectomy
Actual Study Start Date : June 10, 2008
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2019


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.
Drug: Erlotinib Hydrochloride
Given PO
Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva




Primary Outcome Measures :
  1. Response rate (ie: pT0 rate) [ Time Frame: 3-5 weeks of treatment ]

Secondary Outcome Measures :
  1. Disease-free survival [ Time Frame: Up to 5 years ]
  2. Epithelial-mesenchymal transition (EMT) markers [ Time Frame: Baseline up to 5 years ]
    Expression patterns will be correlated with biological responses.

  3. Target inhibition, antiproliferation, and apoptosis in biopsies [ Time Frame: Baseline up to 5 years ]
    Will be quantified.

  4. Interrogate membrane (phosphorylated EGFR) and downstream receptor signaling pathways [ Time Frame: Up to 5 years ]
  5. Changes in Ki-67 expression [ Time Frame: Up to 5 years ]
    Will correlated with changes in angiogenesis and angiogenesis related gene expression utilizing fluorescent tissue staining techniques.

  6. Profile messenger ribonucleic acid (mRNA) expression [ Time Frame: Baseline up to 5 years ]
    The changes observed will be correlated with EMT, growth arrest, and apoptosis.

  7. EGFR copy number [ Time Frame: Baseline up to 5 years ]
    Will be quantified and correlated with changes observed with EMT, growth arrest, and apoptosis.



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00749892


Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Arlene Siefker-Radtke M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00749892     History of Changes
Other Study ID Numbers: 2007-0704
NCI-2018-01833 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2007-0704 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: September 9, 2008    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urethral Neoplasms
Ureteral Neoplasms
Kidney Neoplasms
Pelvic Neoplasms
Carcinoma in Situ
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Ureteral Diseases
Kidney Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action