Gefitinib in Treating Patients With Cervical Cancer
|Phase II||Diagnostic, Treatment||Completed||18 and over||NCI||NCI-02-C-0303|
NCI-5561, 5561, NCT00049556
- 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.
- 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
- No prior cetuximab or monoclonal antibody ABX-EGF
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- At least 4 weeks since prior hormonal therapy and recovered
- No concurrent tamoxifen
- At least 4 weeks since prior radiotherapy and recovered
- Recovered from prior oncologic or other major surgery
- 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)
- 18 and over
- ECOG 0-2
- Not specified
- WBC greater than 3,000/mm3
- Platelet count greater than 100,000/mm3
- Bilirubin less than 1.5 mg/dL
- AST and ALT no greater than 2.5 times upper limit of normal
- Creatinine less than 1.5 mg/dL
- No myocardial infarction within the past 6 months
- No unstable dysrhythmia within the past 6 months
- 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
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)
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
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
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.Published Results
Posadas EM, Liel MS, Kwitkowski V, et al.: A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer. Cancer 109 (7): 1323-30, 2007.[PUBMED Abstract]
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. .
Trial Lead Organizations
NCI - Center for Cancer Research
|Virginia Kwitkowski, MS, RN, CS, CRNP, Protocol chair|
|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|
|Trial Start Date||2002-10-01|
|Registered in ClinicalTrials.gov||NCT00049556|
|Date Submitted to PDQ||2002-09-11|
|Information Last Verified||2006-01-13|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.