Vandetanib to Treat Advanced Kidney Cancer

NCT01372813 | Terminated Phase 2 Results

• 2 other identifiers: 08003908-C-0039
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• One way tumors are able to grow is by forming new blood vessels that supply it with nutrients and oxygen.
• Vandetanib (ZD6474) is an experimental drug that blocks certain proteins on the surface of tumor and blood vessel cells that are involved with the formation of new blood vessels.
• Blocking these proteins may prevent the tumor cells or blood vessels from continuing to grow. Objectives:
• To determine whether vandetanib can cause tumors to shrink or stabilize in patients with advanced kidney cancer.
• To determine how vandetanib may work in people with kidney cancer and to develop tests that may be helpful in studying kidney cancer. Eligibility:
• Patients 18 years of age or older with advanced clear cell kidney cancer whose disease has worsened after treatment with one or more of the following drugs: sunitinib, sorafenib, interleukin-2 and temsirolimus; or patients who have had to stop treatment with these drugs due to unacceptable side effects; or patients who are unable to receive standard treatment. Design:
• Patients take a vandetanib pill once a day in 28-day cycles.
• Patients are followed in the clinic every 2 weeks during the first month of treatment and then every 4 weeks for a physical examination, blood and urine tests, electrocardiogram and a review of any drug side effects.
• Patients have imaging scans (computed tomography (CT) or magnetic resonance imaging (MRI)) about every 8 weeks to monitor tumor growth. MRI scans are also done to look at tumor blood flow when treatment begins, 24 hours after the first dose of treatment, and again about 4 and 8 weeks after starting treatment
• Optional tumor biopsies (surgical removal of a sample of tumor tissue) may be done before starting vandetanib treatment and after 4 weeks of treatment to look for drug effects on the tumor.

Conditions

Advanced Clear Cell Renal Carcinoma

Keywords

Advanced Clear Cell Renal Cell Carcinoma; Cancer; Renal; Renal Cell Carcinoma; Kidney Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Clinical Response (Partial Response (PR) + Clinical Response (CR))

  Clinical response is the best response recorded from the start of treatment until disease progression. Clinical response is assessed by the Response Evaluation in Solid Tumors (RECIST) criteria. A partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. A complete response (CR) is the disappearance of all target lesions.

  12 months

Secondary Outcomes (9)

• Effect of Vandetanib on Plasma Biomarkers-vascular Endothelial Growth Factor (VEGF), Vascular Endothelial Growth Factor 2 (VEGFR2)

  12 months

• Number of Circulating Endothelial Progenitor Cells (CEP) Per 10^6 Mononuclear Cells or Per Microliter of Peripheral Blood Analyzed in Samples Taken Before and After Treatment

  12 months

• Progression-free Survival as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

  12 months

• Number of Participants With Adverse Events

  11.5 months

• Number of Circulating Endothelial Cells (CEC) Per 10^6 Mononuclear Cells or Per Microliter of Peripheral Blood Analyzed in Samples Taken Before and After Treatment

  12 months

Study Arms (1)

Clear Cell Renal Carcinoma

OTHER

Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.

Drug: vandetanib

Interventions

vandetanib DRUG

Daily dose 300mg/day by mouth, 28 day cycle

Also known as: ZD6474

Clear Cell Renal Carcinoma

Eligibility Criteria

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

You may qualify if:

• Patients must meet all the following criteria to be eligible for study enrolment:
• Histologically confirmed clear cell renal cell carcinoma (to be confirmed at the Dept. of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI)).
• Patients must have advanced disease (metastatic or unresectable) disease.
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan.
• See section 6.2 for the evaluation of measurable disease.
• Prior therapy:
• All patients must have either received prior sunitinib or sorafenib (discontinued for disease progression or unacceptable toxicity) or be unable to receive these agents. Patients who have discontinued sunitinib or sorafenib for life threatening toxicities that are also known to occur with vandetanib (such as skin, GI toxicities, bowel perforation etc.) will not be eligible.
• All patients must have failed high dose IL-2, be ineligible to receive this agent or decline this therapy.
• 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 3,000/microL, absolute neutrophil count greater than or equal to 1,500/microL, platelet count greater than or equal to 100,000/microL, 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 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 principal investigator (PI))
• Recovery from acute toxicity of prior treatment for RCC (to less than or equal to grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v3.0).
• At least 4 weeks from completion of major surgery and a healed surgical incision.
• Negative pregnancy test in female patients of childbearing potential within 7 days of enrollment.

You may not qualify if:

• Prior malignancy of other histology, with the exception of cervical carcinoma in situ or adequately treated basal or squamous cell carcinoma of the skin, or any other malignancy for which the patient has not required active treatment for more than three years.
• Patients with VHL disease will be excluded from this study.
• Patients may not be receiving any other investigational agents or have received treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment.
• Patients with known brain metastases (except when adequately treated greater than or equal to 6 months before enrollment with no evidence of recurrence).
• Use of 5HT-3 antagonists because of the potential effect on corrected Q wave, T wave (QTc) interval.
• Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes (Appendix C).
• Drugs listed in Appendix C, Table 2, that in the investigator's opinion cannot be discontinued, are allowed, but must be monitored closely.
• 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.
• Patients with a history a major cardiac event more than 3 months prior to enrolment will be evaluated by a cardiologist to assess cardiac status and potential for increased risk with ZD6474 therapy.
• 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 symptomatic/ 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.

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 (3)

• Zambrano NR, Lubensky IA, Merino MJ, Linehan WM, Walther MM. Histopathology and molecular genetics of renal tumors toward unification of a classification system. J Urol. 1999 Oct;162(4):1246-58.

  PMID: 10492174 BACKGROUND

• Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr. Rising incidence of renal cell cancer in the United States. JAMA. 1999 May 5;281(17):1628-31. doi: 10.1001/jama.281.17.1628.

  PMID: 10235157 BACKGROUND

• Phillips JL, Pavlovich CP, Walther M, Ried T, Linehan WM. The genetic basis of renal epithelial tumors: advances in research and its impact on prognosis and therapy. Curr Opin Urol. 2001 Sep;11(5):463-9. doi: 10.1097/00042307-200109000-00003.

  PMID: 11493766 BACKGROUND

Related Links

• Medline
• Drug Information
• US FDA Resources

MeSH Terms

Conditions

Neoplasms; Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

vandetanib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Study was designed to accrue up to 37 patients but only 3 were enrolled. Study was terminated due to low accrual.

Results Point of Contact

• Title: Marston Linehan, M.D.
• Organization: National Cancer Institute, National Institutes of Health

linehanm@mail.nih.gov

301-496-6353

Study Officials

• W. Marston Linehan, 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: 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: June 11, 2011
• First Posted: June 14, 2011
• Study Start: December 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: October 23, 2015
• Results First Posted: March 12, 2012

Record last verified: 2015-10

Locations

US (1)