Phase II Study of Vandetanib in Individuals With Kidney Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00566995
First received: December 1, 2007
Last updated: July 2, 2014
Last verified: March 2014
  Purpose

This study will examine the effectiveness of an investigational drug called ZD6474 (also known as vandetanib or ZACTIMA). Vandetanib is an experimental drug that is designed to prevent the growth and development of new blood vessels on tumors and to prevent the direct growth of cancer cells. It has been tested in a number of clinical trials on adults with cancer, but the U.S. Food and Drug Administration has not specifically approved it as a cancer treatment. The purpose of this investigational study is to better understand how vandetanib affects humans who have kidney cancer related to von Hippel-Lindau (VHL) disease, and to develop tests that may improve researchers understanding of kidney cancer and its effects.

Volunteers must be at least 18 years old and must have been diagnosed with kidney cancer related to VHL. Candidates must have a life expectancy greater than three months and must have at least one measurable renal tumor for study purposes. Candidates may not be receiving any other investigational agents or have been treated with an investigational drug within the past four weeks. Candidates who have had surgery, chemotherapy, or radiotherapy within the past four weeks will be excluded from the study. Candidates will be screened with a physical examination and medical history.

During the study, participants will receive an oral dose of vandetanib once a day for 28 days (a treatment period known as a cycle). Participants will need to return to the National Institutes of Health every two weeks on the same day of the week as the first dose of vandetanib for a series of tests and procedures, including blood and urine tests and an electrocardiogram. Every 12 weeks, computerized tomography (CT) or magnetic resonance imaging (MRI) scans will be done to assess the size of participants tumors. Participants whose tumors do not grow and who do not have unacceptable side effects may continue to receive vandetanib to maintain the current condition, until researchers conclude the study....


Condition Intervention Phase
Renal Cancer
Von Hippel Lindau
Drug: ZACTIMA (Vandetanib) (ZD6474)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of ZD6474 (Vandetanib) in Patients With Von Hippel Lindau Disease and Renal Tumors

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Overall response rate. [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability. [ Designated as safety issue: Yes ]
  • Time to progression and progression-free survival [ Designated as safety issue: No ]
  • Effect on non-renal Von Hippel-Lindau-associated tumors [ Designated as safety issue: No ]
  • Effect on circulating endothelial cells and endothelial progenitor cells and utility of these markers as surrogates of angiogenesis inhibition [ Designated as safety issue: No ]
  • Effect on plasma VEGF and soluble VEGFR2 [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: November 2007
Estimated Study Completion Date: August 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ZACTIMA (Vandetanib) (ZD6474)
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Patients must satisfy all the following criteria to be eligible for study enrolment.

Clinical diagnosis of von Hippel Lindau disease.

The presence of at least one measurable (as defined by RECIST) renal tumor (RCC). Patients with tumors localized to the kidney as well as those with metastatic RCC are eligible.

Age greater than or equal to 18 years.

Life expectancy greater than 3 months

Performance status ECOG 0-2.

Patients must have normal organ and marrow function as defined below: WBC count greater than or equal to 3,000micro/L, absolute neutrophil count greater than or equal to 1,500 micro/L platelet count greater than or equal to 100,000 micro/L, serum creatinine less than or equal to 1.5 times upper limit of reference range or measured 24 hr. creatinine clearance greater than or equal to 50 ml/min, AST and ALT less than 2.5 times upper limit of reference range, total bilirubin less than 1.5 times upper limit of reference range ( less than 3 times upper limit of reference range in patients with Gilbert s disease), alkaline phosphatase less than or equal to 2.5 times upper limit of reference range (or less than or equal to 5 times upper limit of reference range if considered to be related to liver metastases by the PI).

No history of serious intercurrent medical illness.

At least four weeks from completion of any other surgical or investigational therapy for von Hippel Lindau and at least 4 weeks from any major surgical procedure. In addition, patients who have undergone recent major surgery should have well healed surgical incisions.

All men and women of childbearing potential must use effective contraception.

Negative pregnancy test in female patients of childbearing potential within 7 days prior to enrolment on study

Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Prior or concomitant non-von Hippel Lindau associated malignancy with the exception of adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ or any other malignancy from which the patient has remained disease free for more than five years.

Known brain metastases (unless adequately resected or irradiated with no evidence of recurrence for at least 6 months).

Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events (to less than or equal to grade 1 CTCAE v3.0) due to agents administered more than 4 weeks earlier.

Patients may not be receiving any other investigational agents or have received treatment with a non-approved or investigational drug within 4 weeks prior to Day 1 of study treatment except those used for imaging studies.

Use of 5HT-3 antagonists because of the potential effect on QTc interval.

Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes.

Concomitant medications that are potent inducers of CYP3A4 function, such as rifampin, rifabutin, phenytoin, carbamazapine, barbiturates such as phenobarbital, or St. John s Wort.

Clinically significant cardiac event (including symptomatic heart failure, myocardial infarction or angina) within 3 months of entry or presence of any cardiac disease that in the opinion of the Principal Investigator increases the risk of ventricular arrhythmia.

History of clinically significant arrhythmia [including multifocal premature ventricular contraction (PVC), bigeminy, trigeminy, ventricular tachycardia] that is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia

Uncontrolled atrial fibrillation. Atrial fibrillation controlled on medication is not excluded.

Presence of Left bundle branch block.

Previous history of QTc prolongation while taking other medications that required discontinuation of that medication.

Congenital long QT syndrome or first degree relative with unexplained sudden death under the age of 40 years QTc with Bazett s correction 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 who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is greater than or equal to 460 msec.

Potassium concentration less than 4.0 mEq/L, calcium (ionized calcium or adjusted for albumin), or magnesium concentrations outside normal limits despite optimal supplementation/correction

Left ventricular ejection fraction less than 45 percent measured by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO)

Hypertension not controlled by medical therapy (systolic blood pressure greater than 150 mmHg or diastolic blood pressure greater than 100 mmHg).

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Patient known to be HIV positive and requiring antiretroviral therapy.

Currently active diarrhea that may affect the ability of the patient to absorb ZD6474 or tolerate further diarrhea.

Patients on therapeutic anticoagulation

Patients with known bleeding disorders

Pregnant women are excluded from this study because ZD6474 is an anti-angiogenic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZD6474, breastfeeding should be discontinued if the mother is treated with ZD6474.

Any known hypersensitivity to ZD6474 or other excipients of ZD6474.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00566995

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: W. Marston Linehan, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00566995     History of Changes
Other Study ID Numbers: 080020, 08-C-0020
Study First Received: December 1, 2007
Last Updated: July 2, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Kidney Tumors
Clear Cell Renal Cancer
VEGFR Inhibitor
EGFR Inhibitor
VHL
Von Hippel Lindau
Kidney Tumor

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Von Hippel-Lindau Disease
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neurocutaneous Syndromes
Nervous System Diseases
Angiomatosis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 10, 2014