Vandetanib to Treat Women With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT00445549 | Terminated Phase 2 Results

• 2 other identifiers: 07006107-C-0061
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms

Keywords

Ovarian; VEGFR2; EGFR; Angiogenesis; Tyrosine Kinase; Protein Phosphorylation; Vandetanib; Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinical Efficacy

  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.

  24 weeks

Secondary Outcomes (1)

• The Number of Participants With Adverse Events

  22 months

Study Arms (1)

Vandetanib treatment

EXPERIMENTAL

300 mg daily oral dose, 28 day cycle

Drug: Vandetanib

Interventions

Vandetanib DRUG

300 mg daily dose, 28 day cycle

Also known as: Zactima, ZD6474

Vandetanib treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients 18 years and older with biopsy-proven epithelial ovarian, fallopian tube or primary peritoneal cancer that is relapsed or refractory to prior standard platinum-and taxane based therapy will be eligible.
• Histopathologic diagnosis must be confirmed in the Laboratory of Pathology (LP), NCI. A block of the primary or later access to recut slides is required. If this is unavailable, a recent resection of a metastatic site is required for entry.
• All patients must have measurable disease by NCI RECIST criteria and a sentinel lesion adequate for core biopsy through percutaneous biopsy.
• Patients must have a performance status of Eastern Cooperative Oncology Group (ECOG) = 0, 1, or 2.
• Patients must have good end organ function:
• white blood cells (WBC) greater than 3000/mm(3)
• absolute neutrophil count (ANC) greater than 1000/mm(3)
• platelets greater than 150,000/mm(3)
• serum creatinine less than 1.5 mg/dl
• liver function tests (AST and ALT) within 2.5 times the upper limit of normal (ULN)
• bilirubin less than 1.5 mg/dl
• potassium between 4.0 and ULN (supplementation allowed)
• magnesium (Mg) and calcium (Ca) within normal limits (supplementation allowed)
• Systolic blood pressure less than 160 mm Hg and diastolic blood pressure less than 100 mm Hg (therapy permitted)
• Patients must be at least 4 weeks from previous therapy (chemotherapy, hormonal therapy, and radiation therapy, alternative therapy or investigational agents). Carboplatin, must not have been received for at least 6 weeks prior to enrollment.

You may not qualify if:

• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
• Evidence of central nervous system (CNS) involvement (patients with abnormal clinical exam or history will require a head CT or MRI.
• History of cardiac disorders including:
• Clinically significant cardiac event such as myocardial infarction, New York Heart Association (NYHA) classification of heart disease greater than or equal to 2 within 3 months of entry, or presence of cardiac disease that, in the opinion of the investigator,increases the risk of ventricular arrhythmia.
• Uncontrolled arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic.
• Previous history of medication-induced corrected QT interval (QTc) prolongation requiring discontinuation of that medication.
• Congenital long (Q wave, T wave) QT syndrome, or 1st degree relative with unexplained early sudden cardiac death(less than 40 years of age).
• Presence of left bundle branch block (LBBB).
• QTc, corrected per automated electrocardiogram (ECG) standards, that is unmeasurable, or greater than or equal to 480 msec on screening ECG. If a patient has QTc greater than or equal to 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be less than 480 msec in order for the patient to be eligible for the study.
• Patients requiring any concomitant treatment with medication that may cause QTc prolongation or induce Torsades de Pointes will not be permitted to enter this study unless the agent can safely be changed to one not affecting QTc.
• Patients requiring any concomitant treatment with medication that may inhibit (cytochrome p450 3A4) CYP3A4 will not be permitted to begin this study. If it is considered medically safe to discontinue such medication, the patient may become eligible once a sufficient amount of time after the last dose of such medications has elapsed to consider the drug adequately eliminated (at least 5 half lives of the drug).
• Patients with active infection will not be eligible, but may become eligible once infection has resolved and they are at least 7 days from completion of antibiotics.
• Patients with incomplete wound healing from previous surgery or injury will be ineligible. Patients must be at least 4 weeks from a major surgical procedure.
• Women who are actively breast-feeding will be excluded.
• Currently active diarrhea that is uncontrolled with medication (e.g. bulk agents or loperamide) that may affect the ability of the patient to absorb the ZD6474.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ. Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol. 1995 Jul;147(1):33-41.

  PMID: 7541612 BACKGROUND

• Spentzos D, Levine DA, Ramoni MF, Joseph M, Gu X, Boyd J, Libermann TA, Cannistra SA. Gene expression signature with independent prognostic significance in epithelial ovarian cancer. J Clin Oncol. 2004 Dec 1;22(23):4700-10. doi: 10.1200/JCO.2004.04.070. Epub 2004 Oct 25.

  PMID: 15505275 BACKGROUND

• Ryan AJ, Wedge SR. ZD6474--a novel inhibitor of VEGFR and EGFR tyrosine kinase activity. Br J Cancer. 2005 Jun;92 Suppl 1(Suppl 1):S6-13. doi: 10.1038/sj.bjc.6602603.

  PMID: 15928657 BACKGROUND

• Annunziata CM, Walker AJ, Minasian L, Yu M, Kotz H, Wood BJ, Calvo K, Choyke P, Kimm D, Steinberg SM, Kohn EC. Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2. Clin Cancer Res. 2010 Jan 15;16(2):664-72. doi: 10.1158/1078-0432.CCR-09-2308. Epub 2010 Jan 12.

  PMID: 20068097 RESULT

Related Links

• MedlinePlus
• Drug Information
• U.S. FDA Resources
• RECIST

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms

Interventions

vandetanib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Limitations and Caveats

The study closed after the first stage of accrual because of inadequate early activity with 32 cycles of administered treatment.

Results Point of Contact

• Title: Elise C. Kohn, M.D.
• Organization: National Cancer Institute, National Institutes of Health

kohne@mail.nih.gov

301-496-4916

Study Officials

• Elise C Kohn, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 7, 2007
• First Posted: March 9, 2007
• Study Start: January 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: October 1, 2009
• Last Updated: June 26, 2012
• Results First Posted: June 26, 2012

Record last verified: 2012-05

Locations

US (1)