Gefitinib in Treating Patients With Cervical Cancer

June 18, 2013 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
      • Bethesda, Maryland, United States, 20892
        • NCI - Center for Cancer Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Virginia Kwitkowski, MS, RN, CS, CRNP, National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2002

Study Completion (Actual)

August 1, 2006

Study Registration Dates

First Submitted

November 12, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 20, 2013

Last Update Submitted That Met QC Criteria

June 18, 2013

Last Verified

January 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000258117
  • NCI-02-C-0303
  • NCI-5561

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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