This study is NOT currently recruiting participants.
Number
08-C-0020
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Fetuses;Pregnant Women
Keywords
Kidney Tumors; Clear Cell Renal Cancer; VEGFR Inhibitor; EGFR Inhibitor; VHL
Recruitment Keyword(s)
None
Condition(s)
Renal Cancer; Von Hippel Lindau
Investigational Drug(s)
AZD6474 (Vandetanib)
Investigational Device(s)
Intervention(s)
Drug: ZACTIMA (Vandetanib) (ZD6474)
Supporting Site
National Cancer Institute
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.
--Back to Top--
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.
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.
Principal Investigator
Referral Contact
For more information: