Back to resultsGefitinib in Treating Patients With Cervical Cancer
Primary Purpose
Cervical Cancer, Fallopian Tube Cancer, Ovarian Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
gefitinib
immunohistochemistry staining method
surface-enhanced laser desorption/ionization-time of flight mass spectrometry
biopsy
sentinel lymph node biopsy
Sponsored by
About this trial
This is an interventional treatment trial for Cervical Cancer focused on measuring fallopian tube cancer, borderline ovarian surface epithelial-stromal tumor, primary peritoneal cavity cancer, recurrent cervical cancer, recurrent ovarian epithelial cancer
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)
Sites / Locations
- Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
- NCI - Center for Cancer Research
Outcomes
Primary Outcome Measures
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
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
Full Information
NCT ID
NCT00049556
First Posted
November 12, 2002
Last Updated
June 18, 2013
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00049556
Brief Title
Gefitinib in Treating Patients With Cervical Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2006
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2006 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer
Keywords
fallopian tube cancer, borderline ovarian surface epithelial-stromal tumor, primary peritoneal cavity cancer, recurrent cervical cancer, recurrent ovarian epithelial cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
gefitinib
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Type
Other
Intervention Name(s)
surface-enhanced laser desorption/ionization-time of flight mass spectrometry
Intervention Type
Procedure
Intervention Name(s)
biopsy
Intervention Type
Procedure
Intervention Name(s)
sentinel lymph node biopsy
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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
Title
Clinical activity of gefitinib as measured by CT scan of chest/abdomen/pelvis every 8 weeks
Title
Toxicity as measured by laboratory testing, history, physical exam, and patient diary every 4 weeks
Title
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
Title
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
Title
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
Title
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
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Virginia Kwitkowski, MS, RN, CS, CRNP
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Study Chair
Facility Information:
Facility Name
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1182
Country
United States
Facility Name
NCI - Center for Cancer Research
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
17330838
Citation
Posadas EM, Liel MS, Kwitkowski V, Minasian L, Godwin AK, Hussain MM, Espina V, Wood BJ, Steinberg SM, Kohn EC. A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer. Cancer. 2007 Apr 1;109(7):1323-30. doi: 10.1002/cncr.22545.
Results Reference
result
Citation
Liel MS, Espina V, Pazzagli C, et al.: Phase II study of gefitinib in epithelial ovarian cancer: Proteomic pathway profiling in tumor biopsies. [Abstract] American Association for Cancer Research: 96th Annual Meeting, April 16-20, 2005, Anaheim/Orange County, CA. A-5745, 2005. .
Results Reference
result
Learn more about this trial
Gefitinib in Treating Patients With Cervical Cancer
We'll reach out to this number within 24 hrs