Gefitinib in Treating Patients With Cervical Cancer - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00049556

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 II

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:

MedlinePlus related topics: Cancer Cervical Cancer Ovarian Cancer

Drug Information available for: ZD1839

U.S. FDA Resources

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

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

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

National Cancer Institute (NCI)

Investigators

Study Chair:

Virginia Kwitkowski, MS, RN, CS, CRNP

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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 Mar 1;109(7):1323-1330 [Epub ahead of print]

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:	April 23, 2011
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:

Uterine Cervical Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases

Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012