Clinical Trials /

Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer

NCT01582191

Description:

This phase I trial studies the side effects and best dose of vandetanib and everolimus when given together in treating patients with cancer that has spread to other places in the body. Vandetanib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Cancer
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer
  • Official Title: A Phase 1 Trial of Vandetanib (a Multi-Kinase Inhibitor of EGFR, VEGFR, and RET Inhibitor) in Combination With Everolimus (an mTOR Inhibitor) in Advanced Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2011-0953
  • SECONDARY ID: NCI-2012-00782
  • SECONDARY ID: 0953
  • SECONDARY ID: 2011-0953
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01582191

Conditions

  • Advanced Malignant Neoplasm
  • Metastatic Malignant Neoplasm
  • Recurrent Malignant Neoplasm
  • Refractory Malignant Neoplasm

Interventions

DrugSynonymsArms
Everolimus42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, ZortressTreatment (vandetanib, everolimus)
VandetanibAZD6474, Caprelsa, Zactima, ZD-6474, ZD6474Treatment (vandetanib, everolimus)

Purpose

This phase I trial studies the side effects and best dose of vandetanib and everolimus when given together in treating patients with cancer that has spread to other places in the body. Vandetanib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) or highest dose level, and the dose-limiting
      toxicity (DLT) of vandetanib (a multi-kinase inhibitor of epidermal growth factor receptor
      [EGFR], vascular endothelial growth factor receptor [VEGFR] and ret proto-oncogene [RET]
      inhibitor) when used in combination with everolimus (a mammalian target of rapamycin [mTOR]
      inhibitor) in advanced cancer.

      II. Preliminary descriptive assessment of the anti-tumor efficacy of the combination.

      III. Preliminary optional assessment of the pharmacokinetic, pharmacodynamic markers of
      target inhibition and correlates of response.

      OUTLINE: This is a dose-escalation study.

      Patients receive vandetanib orally (PO) once daily (QD) and everolimus PO QD on days 1-28.
      Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment patients are followed up between 14-28 days at the
      discretion of the treating physician.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (vandetanib, everolimus)ExperimentalPatients receive vandetanib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Everolimus
  • Vandetanib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with advanced or metastatic cancer that is refractory to standard therapy,
             relapsed after standard therapy, or who have no standard therapy available that
             improves survival by at least three months

          -  Patients must be at least 3 weeks beyond their previous cytotoxic chemotherapy;
             patient must be at least 5 half-lives or 3 weeks, whichever is shorter, from their
             previous targeted or biologic therapy; in addition, patients must be at least 3 weeks
             beyond the last session of radiation therapy; local palliative radiation therapy that
             is not delivered to all target lesions is allowed immediately before or during
             treatment

          -  Eastern Cooperative Oncology Group (ECOG) performance status should be less or equal
             to 3

          -  Absolute neutrophil count more or equal to 750/mL

          -  Platelets more or equal to 50,000/mL

          -  Creatinine less or equal to 3 x upper limit of normal (ULN)

          -  Total bilirubin less than or equal to 3.0

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence)

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including, but not limited to, uncontrolled
             infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support

          -  Pregnant or lactating women

          -  History of hypersensitivity to vandetanib, lactose, murine products, or any component
             of the formulation

          -  History of hypersensitivity to sirolimus, temsirolimus, everolimus

          -  History of hypersensitivity to any component of the formulation

          -  Patients unwilling or unable to sign informed consent document

          -  Presence of cardiac disease that, in the opinion of the investigator, increases the
             risk of ventricular arrhythmia

          -  History (within the last 3 months) or presence of stroke/cerebrovascular accident

          -  Congenital long QT syndrome

          -  Corrected QT for Fridericia (QTcF) interval greater than 500 ms that is not
             correctable to less than 500 ms such as with cessation of a causative medication, etc

          -  History of myocardial infarction within 6 months with a residual arrhythmia that in
             the opinion of the investigator, increases the risk of ventricular arrhythmia

          -  Presence of a symptomatic bradyarrhythmia or uncompensated heart failure
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:28 days
Safety Issue:
Description:Will be defined as the highest dose studied in which the incidence of dose limiting toxicity was less than 33%. Toxicity will be reported by type, frequency, and severity. Worst toxicity grades per patient will be tabulated for selected adverse events and laboratory measurements.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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