Vandetanib to Treat Women With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
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|ClinicalTrials.gov Identifier: NCT00445549|
Recruitment Status : Terminated (The study closed because of inadequate early activity.)
First Posted : March 9, 2007
Results First Posted : June 26, 2012
Last Update Posted : June 26, 2012
- Vandetanib is a drug that attacks a group of proteins on the surface of many cells, especially blood vessel cells and tumor cells.
- Tumors require the development of new blood vessels in order to grow and spread.
- In laboratory experiments, vandetanib slowed the growth of certain tumors and regulated their blood vessel growth.
- In early clinical trials, some patients' tumors did not grow for a period of time while they were receiving vandetanib.
- To determine whether vandetanib can cause tumors to shrink or stabilize in some patients with ovarian cancer, fallopian tube cancer or primary peritoneal cancer.
- To determine, by tumor biopsy, if features of the tumor change with vandetanib treatment may predict if the tumor will likely respond to vandetanib.
- Women 18 years of age and older with ovarian, fallopian tube or primary peritoneal cancer that does not respond to standard treatment.
- Patients take vandetanib daily, by mouth in 28-day cycles until their disease worsens or they develop unacceptable side effects.
- Tumor biopsies (surgical removal of a sample of tumor tissue) are done before starting vandetanib treatment and after 6 weeks of treatment.
- Patients are followed in the clinic every 4 weeks during treatment for a physical examination, blood tests, and review of laboratory studies and side effects.
- Patients have a computed tomography (CT) scan every 8 weeks to monitor tumor growth and magnetic resonance imaging (MRI) before starting vandetanib treatment, on the third day after taking vandetanib and 6 weeks into treatment.
- Patients quality of life is assessed with regularly scheduled questionnaires.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Neoplasms Fallopian Tube Neoplasms Peritoneal Neoplasms||Drug: Vandetanib||Phase 2|
- Epithelial ovarian cancer requires neovascularization for growth and metastasis. Anti-angiogenesis agents have been shown to have promise in the treatment of recurrent disease. Expression of vascular endothelial growth factor 2 (VEGFR2) and epidermal growth factor receptor (EGFR) has been demonstrated in ovarian cancer specimens in stroma and tumor. Blocking autocrine and paracrine loops acting through these receptors may inhibit downstream phosphorylation targets in the mitogen activated protein kinase (MAPK) and AKT pathways, thereby influencing disease progression and patient outcome.
- The multi-kinase inhibitor ZD6474 (vandetanib, AstraZeneca, Zactima) blocks angiogenesis by targeting VEGFR2, and shows in vitro activity against a number of other receptor tyrosine kinases including resonance energy transfer (RET), vascular endothelial growth factor 3 (VEGFR3) and EGFR.
- Clinical efficacy of ZD6474 (vandetanib) in women with refractory or relapsed epithelial ovarian cancer is unknown, but preclinical data suggests potential value.
- The maximum tolerated dose of ZD6474 (vandetanib) has been determined at 300mg/day, limited by the dose-responsive adverse effect of prolonged (Q wave, T wave)QT interval.
- To assess the clinical activity (CR - complete response, PR - partial response, or disease stabilization) of the VEGFR2 inhibitor ZD6474 (vandetanib), 300mg/d, in women with ovarian, fallopian tube or primary peritoneal cancer.
- To study target signal events: quantity and activation of VEGFR2, EGFR, AKT and extracellular signal-regulated kinases (ERK).
- Women with biopsy-proven epithelial ovarian, fallopian tube or primary peritoneal cancer that is relapsed and/or refractory to prior therapy.
- Women must have measurable disease by NCI Response Evaluation Criteria in Solid Tumors (RECIST) criteria and a sentinel lesion adequate for core biopsy through percutaneous biopsy.
- Women must have had no more than four prior treatment regimens.
- Women will receive 300mg of ZD6474 (vandetanib) daily, orally in 28-day cycles until disease progression, excessive toxicity, or withdrawal from study.
- Biopsy of tumor will be performed prior to starting ZD6474 (vandetanib) and after six weeks of treatment. The quantity of phosphorylated VEGFR2, EGFR, ERK and AKT in the biopsy tissue will be analyzed.
- Clinical outcome and toxicity will be measured and correlated with target inhibition.
- Women will also undergo serial imaging with dynamic contrast-enhanced MRI to estimate tumor blood flow.
- Research blood samples will be taken to assess changes in circulating cytokine concentrations.
- Quality of life will be assessed during treatment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Clinical Activity and Proteomic Pathway Profiling of the Vascular Endothelial Growth Factor 2 (VEGFR2) Inhibitor, ZD6474 (Vandetanib) in Women With Relapsed or Refractory Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer|
|Study Start Date :||January 2007|
|Actual Primary Completion Date :||December 2008|
|Actual Study Completion Date :||October 2009|
Experimental: Vandetanib treatment
300 mg daily oral dose, 28 day cycle
300 mg daily dose, 28 day cycle
- Number of Participants With Clinical Efficacy [ Time Frame: 24 weeks ]Defined as complete response (CR), partial response (PR), or disease stabilization lasting 6 months or longer per RECIST criteria. CR-total disappearance of all evaluable disease. PR->30% reduction in the sum of the longest diameters (LD) of target lesions. Stable disease (SD) is <30% decrease and <20% increase in the sum of the LD of all target lesions. See the protocol Link module for full RECIST criteria.
- The Number of Participants With Adverse Events [ Time Frame: 22 months ]Here are the total # of participants with adverse events. For the detailed list of adverse events, see the adverse event module.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00445549
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Elise C Kohn, M.D.||National Cancer Institute, National Institutes of Health|