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Dose Escalation Study of Vandetanib With Hypofractionated Stereotactic Radiotherapy in Recurrent Malignant Gliomas (IRUSZACT0073)

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00822887
First received: January 13, 2009
Last updated: June 24, 2013
Last verified: June 2013
  Purpose

The purpose of the study is to find out the highest dose of vandetanib that can be safely given with repeat radiation therapy.

This study drug has been designed to block certain chemical pathways that stimulate tumor to grow. The study drug has been shown to slow the growth of a number of types of cancers.

This will be a dose escalation study. A dose escalation study means that successive groups of patients will receive higher doses of the study drug. There are three dose levels. The dose of the study drug received will depend on the stage the study has reached at the time a patient decides to participate.

In addition to taking the study drug patients will also receive radiation therapy to the brain tumor for 3 days.

Hypothesis The objective of this study is to determine the maximally tolerated dose (MTD) of VANDETANIB given with 36 Gy hypofractionated stereotactic radiotherapy. The MTD will be dose of VANDETANIB at which no patients develop acute grade 5 toxicity and less than 30% of patients develop acute (within 30 days of radiation therapy) or delayed (at least 30 days after radiation completed) dose limiting toxicities.


Condition Intervention Phase
Malignant Gliomas
Drug: Vandetanib
Radiation: Fractionated Stereotactic Radiotherapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of Vandetanib (ZACTIMA, ZD6474) With Hypofractionated Stereotactic Radiotherapy in Patients With Recurrent Malignant Gliomas

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Incidence of acute and delayed ≥ grade 3 Central nervous system (CNS) toxicity by Common Terminology Criteria (CTC) v.3. [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of acute and delayed ≥ grade 3 non-CNS toxicity [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
  • Progression-free survival at 6 months [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
  • Objective response rate [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
  • Quality of survival [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: March 2007
Study Completion Date: January 2011
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vandetanib
Dose level 1:100 mg qd, 2:200 mg qd, 3:300 mg qd. Fractionated Stereotactic Radiotherapy: all patients will receive 36 Gy of radiation in three fractions, given in three consecutive days.
Drug: Vandetanib
Dose level 1:100 mg qd Dose level 2:200 mg qd Dose level 3:300 mg qd
Other Name: ZD6474, Zactima
Radiation: Fractionated Stereotactic Radiotherapy
All patients will receive 36 Gy of radiation in three fractions, given in three consecutive days.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histopathologically confirmed malignant gliomas that recurred after surgical resection and conventional radiation therapy
  • Tumor is not located in the eloquent part of the brain and not touching the brainstem, optic chiasm or optic nerve so that these critical structures will not receive full dose of re-irradiation
  • Recurrent tumor is not surgically resectable or patient is not medically operable
  • Age > 18 years.
  • Radiographical evidence of local recurrence on brain MRI, with or without histopathological confirmation.
  • Estimated survival of at least 3 months
  • Zubrod Performance Scale of 0-2
  • Hgb greater than 10 gm/dl, absolute neutrophil count greater than 1500/ul, platelets greater than 100,000/ul, blood urea nitrogen (BUN) less than 25 mg/dl, Bilirubin less than 2.0 mg/dl, serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) less than 2 x normal range
  • Less than or equal to 3 recurrent tumors, and combined largest diameter of all tumors less than or equal to 6 cm
  • Single recurrent tumor less than or equal to 6 cm in the largest diameter

Exclusion Criteria:

  • Prior therapy with any anti-Epidermal growth factor receptor(EGFR) and/or anti-VEGFR therapies
  • Recurrent tumor greater than 6 cm in the largest diameter
  • Recurrent tumor located in the brainstem.
  • Prior radiation therapy to the brain within 2 months.
  • Evidence of severe or uncontrolled systemic disease or any concurrent condition (such as severe cognitive impairment)
  • pregnant and breast-feeding women will be excluded
  • Treated on any other clinical protocols or with a non-approved or investigational drug within 30 days before Day 1 of study treatment.
  • Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
  • Clinically significant cardiac event
  • History of arrhythmia. Atrial fibrillation, controlled on medication is not excluded.
  • Previous history of corrected electrocardiogram QT interval (QTc)prolongation as a result from other medication that required discontinuation of that medication.
  • Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
  • Presence of left bundle branch block QTc with Bazett's correction that is unmeasurable, or 480 msec on screening ECG. If a patient has QTc 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.
  • Concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce cytochrome P450 3A4 (CYP3A4) function Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
  • Active diarrhea that may affect the ability of the patient to absorb the VANDETANIB.
  • Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
  • Clinical and/or radiographic evidence of bleeding in the recurrent brain tumor.
  • Patients currently on enzyme inducing anticonvulsants. However, patients are eligible if the enzyme inducing anticonvulsants can be discontinued or switched to non- enzyme inducing anticonvulsants one week before study entry. Non-enzyme inducing anticonvulsants cannot be those which may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
  • Laboratory results:

    • Serum bilirubin greater than 1.5 x the upper limit of reference range (ULRR)
    • Serum creatinine greater than 1.5 x ULRR or creatinine clearance less than 50 mL/minute (calculated by Cockcroft-Gault formula)
    • Potassium, less than 4.0 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium out of normal range despite supplementation
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 X ULRR
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00822887

Locations
United States, Colorado
University of Colorado Health Science Center
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
AstraZeneca
Investigators
Principal Investigator: Changhu Chen, MD University of Colorado, Denver
  More Information

No publications provided by University of Colorado, Denver

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00822887     History of Changes
Obsolete Identifiers: NCT00721292
Other Study ID Numbers: 06-0870.cc
Study First Received: January 13, 2009
Last Updated: June 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
malignant
gliomas

Additional relevant MeSH terms:
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on November 24, 2014