Vandetanib and Temozolomide in Treating Patients With Advanced Solid Tumors That Cannot Be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00601614
Recruitment Status : Withdrawn (no enrollment)
First Posted : January 28, 2008
Last Update Posted : March 10, 2014
National Cancer Institute (NCI)
Information provided by:
Mayo Clinic

Brief Summary:

RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vandetanib together with temozolomide may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vandetanib and temozolomide in treating patients with advanced solid tumors that cannot be removed by surgery.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: temozolomide Drug: vandetanib Other: immunoenzyme technique Other: laboratory biomarker analysis Phase 1

Detailed Description:


  • To determine the maximum tolerated dose of concurrently administered vandetanib and temozolomide in patients with unresectable, advanced solid tumors.
  • To describe the toxicity profile of this regimen in these patients.
  • To describe the response rate in patients treated with this regimen.
  • To describe the effects of therapy on angiogenesis-related translational endpoints.

OUTLINE: Patients receive escalating doses of oral vandetanib once daily on days 1-28 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and prior to each treatment course for correlative laboratory studies, including evaluation of plasma VEGF levels by ELISA, serum angiogenesis assay, and measurement of circulating endothelial cell populations (CD133, CD34, CD146). Frozen serum and plasma samples are also stored for future research studies.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Primary Purpose: Treatment
Official Title: Phase I Study of ZD6474 and Temozolomide in Patients With Advanced Cancer
Study Start Date : January 2008
Estimated Primary Completion Date : January 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. Maximum tolerated dose of vandetanib and temozolomide
  2. Adverse events profile
  3. Toxicity profile
  4. Response profile
  5. Time until any treatment-related toxicity
  6. Time until treatment-related grade 3+ toxicity
  7. Time until hematologic nadirs
  8. Time to progression
  9. Time to treatment failure
  10. Correlation of changes in VEGF levels, serum angiogenesis, and circulating endothelial cells with response and dose levels

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed solid tumor

    • Unresectable, advanced disease
  • Measurable or evaluable disease
  • No known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
  • No intracranial metastatic disease, unless it has been radiologically and clinically stable for the past 3 months


  • ECOG performance status 0-2
  • ANC ≥ 1,500/μL
  • Absolute lymphocyte count > 1,000/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN (≤ 5 times ULN if liver involvement)
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance > 50 mL/min
  • Potassium normal
  • Serum calcium (ionized or adjusted for albumin) normal
  • Magnesium normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No currently active diarrhea that results in an ongoing need for IV fluids and/or that may affect the ability of the patient to absorb vandetanib or tolerate diarrhea
  • No evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or that would jeopardize compliance with the study
  • No other malignancies within the past 5 years, except cervical carcinoma in situ or adequately treated basal cell or squamous cell carcinoma of the skin
  • No clinically significant cardiac event, such as myocardial infarction, NYHA class II-IV heart disease within the past 3 months, or presence of cardiac disease that, in the opinion of the treating physician, increases the risk of ventricular arrhythmia
  • No history of arrhythmia (i.e., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (CTCAE grade 3)

    • Atrial fibrillation that is controlled on medication allowed
  • No asymptomatic sustained ventricular tachycardia
  • No history of QTc prolongation as a result of other medication that required discontinuation of that medication
  • No congenital long QT syndrome
  • No 1st degree relative with unexplained sudden death under 40 years of age
  • No left bundle branch block
  • No QTc with Bazett's correction that is unmeasurable
  • QTc < 480 msec on screening ECG
  • No hypertension that is uncontrolled by medical therapy (i.e., systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg)
  • No bleeding diathesis (inherited coagulopathy)


  • Recovered from prior therapy
  • More than 30 days since prior investigational agents
  • More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
  • More than 4 weeks since prior immunotherapy or biologic therapy
  • More than 4 weeks since prior major surgery

    • Surgical incision must be completely healed
  • More than 4 weeks since prior radiotherapy, except palliative radiotherapy
  • No prior radiotherapy to > 25% of bone marrow
  • No prior temozolomide or dacarbazine
  • No prior enrollment in this study
  • More than 2 weeks since prior and no concurrent known potent CYP3A4 inducers, such as rifampin, phenytoin, carbamazepine, barbiturates, or St. John's wort
  • More than 2 weeks since prior and no concurrent drugs associated with an increased risk of causing Torsades de Pointes
  • No concurrent medication that may cause QTc prolongation
  • No concurrent anticoagulants
  • No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00601614

Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Ravi D. Rao, MD, MBBS Mayo Clinic
OverallOfficial: Svetomir Markovic, MD, PhD Mayo Clinic Identifier: NCT00601614     History of Changes
Other Study ID Numbers: MC0615
First Posted: January 28, 2008    Key Record Dates
Last Update Posted: March 10, 2014
Last Verified: March 2014

Keywords provided by Mayo Clinic:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents