Ignite Creation Date:
2024-05-05 @ 5:24 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00445549
Status:
TERMINATED
Last Update Posted:
2012-06-26
First Post:
2007-03-07
Brief Title:
Vandetanib to Treat Women With Ovarian Fallopian Tube or Primary Peritoneal Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
TERMINATED
Status Verified Date:
2012-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The study closed because of inadequate early activity
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
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
Objectives
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
Eligibility
Women 18 years of age and older with ovarian fallopian tube or primary peritoneal cancer that does not respond to standard treatment
Design
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
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
Objectives
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
Eligibility
Women 18 years of age and older with ovarian fallopian tube or primary peritoneal cancer that does not respond to standard treatment
Design
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
Detailed Description:
Background
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 300mgday limited by the dose-responsive adverse effect of prolonged Q wave T waveQT interval
Objectives
To assess the clinical activity CR - complete response PR - partial response or disease stabilization of the VEGFR2 inhibitor ZD6474 vandetanib 300mgd 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
Eligibility
Women with biopsy-proven epithelial ovarian fallopian tube or primary peritoneal cancer that is relapsed andor 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
Design
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
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 300mgday limited by the dose-responsive adverse effect of prolonged Q wave T waveQT interval
Objectives
To assess the clinical activity CR - complete response PR - partial response or disease stabilization of the VEGFR2 inhibitor ZD6474 vandetanib 300mgd 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
Eligibility
Women with biopsy-proven epithelial ovarian fallopian tube or primary peritoneal cancer that is relapsed andor 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
Design
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 070061 | OTHER | Clinical Center CC National Institutes of Health NIH | None |
| 07-C-0061 | OTHER | None | None |