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Gefitinib in Treating Patients With Cervical Cancer

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00049556
First received: November 12, 2002
Last updated: June 18, 2013
Last verified: January 2006
  Purpose

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.


Condition Intervention Phase
Cervical Cancer
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Drug: gefitinib
Other: immunohistochemistry staining method
Other: surface-enhanced laser desorption/ionization-time of flight mass spectrometry
Procedure: biopsy
Procedure: sentinel lymph node biopsy
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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 [ Designated as safety issue: No ]

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 [ Designated as safety issue: No ]
  • Clinical activity of gefitinib as measured by CT scan of chest/abdomen/pelvis every 8 weeks [ Designated as safety issue: No ]
  • Toxicity as measured by laboratory testing, history, physical exam, and patient diary every 4 weeks [ Designated as safety issue: Yes ]
  • 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 [ Designated as safety issue: Yes ]
  • 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 [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: Yes ]

Study Start Date: October 2002
Study Completion Date: August 2006
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049556

Locations
United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Virginia Kwitkowski, MS, RN, CS, CRNP National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
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. .

ClinicalTrials.gov Identifier: NCT00049556     History of Changes
Obsolete Identifiers: NCT00046007
Other Study ID Numbers: CDR0000258117, NCI-02-C-0303, NCI-5561
Study First Received: November 12, 2002
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
fallopian tube cancer
borderline ovarian surface epithelial-stromal tumor
primary peritoneal cavity cancer
recurrent cervical cancer
recurrent ovarian epithelial cancer

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Uterine Cervical Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Gefitinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014