Phase II Study of Vandetanib in Individuals With Kidney Cancer

NCT00566995 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 08002008-C-0020
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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 United States (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....

Conditions

Renal Cancer; Von Hippel Lindau

Keywords

Kidney Tumors; Clear Cell Renal Cancer; VEGFR Inhibitor; EGFR Inhibitor; VHL; Von Hippel Lindau; Kidney Tumor

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate.

  Overall response rate is defined as the percentage of participants with either a partial or complete response occurring at any time after initiation of therapy. Response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST). Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Complete response (CR) is a disappearance of all target lesions. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (progressive disease), taking as reference the smallest sum LD since the treatment started.

  Baseline and every 3 cycles, up to 2 years

Secondary Outcomes (8)

• Number of Participants With Adverse Events

  72 months and 14 days

• Time To Progression (TTP)

  Baseline and every 3 cycles while on study, up to 2 years.

• Progression Free Survival (PFS)

  Baseline and every 3 cycles while on study, up to 2 years.

• Effect of Vandetanib (ZD6474) on Endothelial Progenitor Cells

  Pre treatment, 4 hours after first treatment, and after one cycle of treatment (one cycle = 28 days)

• Effect of Vandetanib (ZD6474) on Circulating Endothelial Cells (CEC)

  Pre treatment, 4 hours after first treatment, and after one cycle of treatment (one cycle = 28 days)

Other Outcomes (1)

• Change in Plasma Biomarkers Vascular Endothelial Growth Factor (VEGF) and Soluble Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Before and After Treatment With Vandetanib

  Pre treatment, 4 hours after first treatment, and after one cycle of treatment (one cycle = 28 days)

Study Arms (1)

Vandetanib in Participants with Kidney Cancer

EXPERIMENTAL

300 mg/day (starting dose) oral dose of vandetanib once a day for 28 days

Drug: ZACTIMA (Vandetanib) (ZD6474)

Interventions

ZACTIMA (Vandetanib) (ZD6474) DRUG

Also known as: Vandetanib

Vandetanib in Participants with Kidney Cancer

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (renal cell carcinoma (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 Eastern Cooperative Oncology Group (ECOG) 0-2.
• Patients must have normal organ and marrow function as defined below: white blood cell (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, aspartate aminotransferase (AST) and alanine aminotransferase (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 Gilberts 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 principal investigator (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.

You may not qualify if:

• 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 Common Terminology Criteria in Adverse Events (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 corrected QT interval (QTc) interval.
• Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes.
• Concomitant medications that are potent inducers of cytochrome P450 3A4 (CYP3A4) function, such as rifampin, rifabutin, phenytoin, carbamazepine, barbiturates such as phenobarbital, or St. Johns 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 Bazetts correction that is unmeasurable, or greater than or equal to 480 msec on screening electrocardiogram (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)

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 (6)

• Linehan WM, Lerman MI, Zbar B. Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer. JAMA. 1995 Feb 15;273(7):564-70. No abstract available.

  PMID: 7837390 BACKGROUND

• Clifford SC, Maher ER. Von Hippel-Lindau disease: clinical and molecular perspectives. Adv Cancer Res. 2001;82:85-105. doi: 10.1016/s0065-230x(01)82003-0.

  PMID: 11447766 BACKGROUND

• Kaelin WG Jr. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer. 2002 Sep;2(9):673-82. doi: 10.1038/nrc885.

  PMID: 12209156 BACKGROUND

• Brooks S, Linehan WM, Srinivasan R, Kong HH. Successful laser treatment of vandetanib-associated cutaneous pigmentation. Arch Dermatol. 2011 Mar;147(3):364-5. doi: 10.1001/archdermatol.2011.30. No abstract available.

  PMID: 21422355 BACKGROUND

• Vitael, S, Cunningham, D. Meleth, A., Bishop R., Clayton, Datile, M, Linehan WM, Srinivasan R, Meyerle, C. Development of a New Grading System for Corneal Verticillata. ARVO meeting May 8, 2013

  BACKGROUND

• Vitael, S, Cunningham, D. Meleth, A., Bishop R., Clayton, Datile, M, Linehan WM, Srinivasan R, Meyerle, C. Development of a New Grading System for Corneal Verticillata. ARVO meeting May 2012.

  BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

vandetanib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Dr. W. Marston Linehan
• Organization: National Cancer Institute

linehanm@mail.nih.gov

301-496-6353

Study Officials

• W. Marston Linehan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 1, 2007
• First Posted: December 4, 2007
• Study Start: February 7, 2008
• Primary Completion: June 20, 2014
• Study Completion: March 1, 2015
• Last Updated: October 30, 2018
• Results First Posted: March 11, 2015

Record last verified: 2018-10

Locations

US (1)