Gefitinib in Treating Patients With Cervical Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of cervical cancer. Comparing results of diagnostic procedures performed before, during, and after treatment with gefitinib may help doctors predict a patient's response to treatment and help plan the most effective treatment. PURPOSE: This phase II trial is studying how well gefitinib works in treating patients with cervical cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the reduction in phosphorylation of epidermal growth factor receptor (EGFR), AKT, and ERK by proteomics in tumor and normal skin of patients with ovarian epithelial cancer or cervical cancer receiving gefitinib. (Open to accrual for cervical cancer patients only as of 4/5/2005) Determine the clinical activity of this drug in these patients. Determine the toxicity of this drug in these patients. Correlate the biologic modulation of EGFR, ERK, and AKT by this drug with outcome and toxic effects in these patients. Correlate EGFR modulation in skin with outcome and toxic effects in patients treated with this drug. Correlate expression of EGFR and phosphorylated-EGFR in tissue biopsies from these patients with biochemical modulation and outcome. Determine the application of surface-enhanced laser desorption and ionization with time-of-flight detection (SELDI-TOF) and artificial intelligence bioinformatics to serially obtained serum samples for predicting response and toxic effects in these patients. OUTLINE: Patients are stratified according to disease (cervical cancer vs ovarian epithelial, fallopian tube, and primary peritoneal cancer). (Open to accrual for cervical cancer patients only as of 4/5/2005) Patients receive oral gefitinib daily. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Biopsies of a sentinel lesion (with CT guidance or laparoscopy) are obtained at baseline and at 4 weeks. Skin biopsies of unaffected areas are also obtained at these time points. Tissue is examined using immunohistochemical methods. Proteomic profiling using surface-enhanced laser desorption/ionization with time-of-flight (SELDI-TOF) mass spectrometry is conducted on serum at baseline and then every 4 weeks. Patients are followed monthly. PROJECTED ACCRUAL: A total of 30-40 patients (15-20 per stratum) will be accrued for this study within 10-12 months. (Open to accrual for cervical cancer patients only as of 4/5/2005)

Official Title
-----------------
Phase II Pilot Study of Clinical Activity and Proteomic Pathway Profiling of the EGFR Inhibitor, ZD1839 (Iressa; Gefitinib), in Patients With Epithelial Ovarian Cancer or Cervical Cancer

Conditions
-----------------
Cervical Cancer, Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
-----------------
* Drug: gefitinib
* Other: immunohistochemistry staining method
* Other: surface-enhanced laser desorption/ionization-time of flight mass spectrometry
* Procedure: biopsy
* Procedure: sentinel lymph node biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed ovarian epithelial cancer or cervical cancer (open to accrual for cervical cancer patients only as of 4/5/2005) Relapsed or refractory The following are also eligible: (open to accrual for cervical cancer patients only as of 4/5/2005) Cancer of the fallopian tube Primary peritoneal cancer Cancer with low malignant potential and an invasive recurrence Block or recuts of primary tumor or recent resection specimen of a metastatic site required Measurable disease with a sentinel lesion adequate for core biopsy by percutaneous biopsy or laparoscopy No CNS involvement PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic WBC greater than 3,000/mm^3 Platelet count greater than 100,000/mm^3 Hepatic Bilirubin less than 1.5 mg/dL AST and ALT no greater than 2.5 times upper limit of normal Renal Creatinine less than 1.5 mg/dL Cardiovascular No myocardial infarction within the past 6 months No unstable dysrhythmia within the past 6 months Other No other invasive malignancy within the past 5 years except noninvasive nonmelanoma skin cancer No active ocular inflammation or infection No active infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after study PRIOR CONCURRENT THERAPY: Biologic therapy No prior cetuximab or monoclonal antibody ABX-EGF Chemotherapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Endocrine therapy At least 4 weeks since prior hormonal therapy and recovered No concurrent tamoxifen Radiotherapy At least 4 weeks since prior radiotherapy and recovered Surgery Recovered from prior oncologic or other major surgery Other No prior epidermal growth factor receptor inhibitory agents (e.g., OSI-774) No concurrent antiretroviral therapy No concurrent itraconozole, ketoconazole, erythromycin, verapamil, chlorpromazine, amiodarone, or chloroquine No concurrent drugs known to induce CYP3A4 enzymes (e.g., phenytoin, carbamazepine, rifampicin, barbiturates, oxacarbazepine, rifapentine, or Hypericum perforatum)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gefitinib|nan|
|Other: immunohistochemistry staining method|nan|
|Other: surface-enhanced laser desorption/ionization-time of flight mass spectrometry|nan|
|Procedure: biopsy|nan|
|Procedure: sentinel lymph node biopsy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochem. modulation of EGFR signal transduction pathways in tumor by tissue lysate array reduction in phosphorylation of EGFR , AKT, and ERK in tumor biopsies at baseline and at 4 weeks during therapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochem. modulation of EGFR signal transduction pathways in skin biopsy tissue by tissue lysate array reduction in phosphorylation of EGFR , AKT, and ERK in skin biopsies at baseline and at 4 weeks during therapy |  |  | 
| Clinical activity of gefitinib as measured by CT scan of chest/abdomen/pelvis every 8 weeks |  |  | 
| Toxicity as measured by laboratory testing, history, physical exam, and patient diary every 4 weeks |  |  | 
| Skin as a surrogate site for study of EGFR modulation and correlation with outcome and toxicity as measured by tissue lysate arrays at baseline and 4 weeks after the start of study therapy |  |  | 
| Potential collateral activation of other signal pathways in tumor and skin as measured by tissue lysate arrays at baseline and 4 weeks after the start of study therapy |  |  | 
| Expression of EGFR and phosphorylated-EGFR (pY-EGFR) as measured by tissue lysate arrays at baseline and 4 weeks after the start of study therapy |  |  | 
| Prediction of response and/or toxicity by serially obtained serum samples using surface-enhanced laser desorption and ionization with time-of-flight detection (SELDI-TOF) and artificial intelligence bioinformatics at baseline and then monthly |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
fallopian tube cancer, borderline ovarian surface epithelial-stromal tumor, primary peritoneal cavity cancer, recurrent cervical cancer, recurrent ovarian epithelial cancer