MDACC Study Summary 2007-0704

Study Summary
No. 2007-0704:.......Bladder......Arlene Siefker-Radtke......Genitourinary Medical Oncology

Study Summary Title



Study Summary Number:	2007-0704

Study Title:	A Phase II Exploratory Study of Pre-Operative Treatment with Erlotinib (Tarceva) in Muscle Invasive or Recurrent Transitional Cell Carcinoma Requiring Cystectomy

Physician

New Patient Referral



Name:	Arlene Siefker-Radtke	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Genitourinary Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2830 Contact us about clinical trials

General Information



Disease Group:	Bladder	Supported By:	Genentech, Inc.

Phase of Study:	Phase II	Return Visit:	Patient will return for blood testing and toxicity assessments weekly while receiving Tarceva.

Treatment Agents:	Tarceva	Home Care:	Patients will self-adminsiter the study drug daily.

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goal of this clinical research study is to learn if Tarceva™ (erlotinib hydrochloride; OSI-774) can help to shrink the tumor or slow its growth, before surgery, in patients with transitional cell carcinoma.

Study Objectives / Outcomes

Primary Objectives

1. To estimate the response rate (ie: pT0 rate) of patients with urothelial cancer treated with erlotinib prior to cystectomy. In this context, response will be defined as the absence of residual cancer in the resected specimen.

Secondary Objectives

Clinical Objectives:

1. To estimate the 4-year disease-free survival of patients with urothelial cancer treated with erlotinib prior to cystectomy.

Biologic Objectives:

1. To measure 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.

2. To quantify target inhibition, antiproliferation (KI-67), and apoptosis (TUNEL) in biopsies obtained from patients before, during, and after therapy.

3. 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.

4. 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.)

5. To profile mRNA expression in pre- and post-treatment biopsies using Affymetrix arrays and correlate the changes observed with EMT, growth arrest, and apoptosis.

6. To quantify EGFR copy number and correlate with changes observed with EMT, growth arrest, and apoptosis.

Study Status Information



Study Activation / Registration Date:	06/10/2008

IRB Review and Approval Date:	12/05/2007

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) 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.

2) Patients with the following high-risk features: Micropapillary features (more than focal on pathology); Small cell carcinoma; 3-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 CT or MRI imaging;

3) (# 2 cont'd) 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.

4) 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.

5) Patients must have an evaluation in the department of urology, and be deemed an acceptable surgical candidate.

6) 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 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.

7) Individuals must be > 18 years of age. In general, urothelial cancer occurs in the 6th to 7th decade of life, so it is unlikely that pediatric patients will be included.

8) 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.

9) Bone marrow function: absolute neutrophil count (ANC) >/= 1,000/ul; platelets >/= 75,000/microliters.

10) Renal function: 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.

11) Hepatic function: bilirubin </= 2.5 x ULN; AST </= 5.0 x ULN.

12) Zubrod PS </= 2.

13) 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:

1) Acute hepatitis or known HIV.

2) Active or uncontrolled infection.

3) 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%.

4) Prior therapy specifically and directly targeting the EGFR pathway.

5) Patients with interstitial lung disease.

6) Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).

7) 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.

8) Patients who have received prior systemic chemotherapy or radiation therapy for urothelial cancer are not eligible. Any prior intravesical chemotherapy is allowed.

Links

Registration Number: NCT00749892
Study Information on Clinical Trials Registry (clinicaltrials.gov)