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

NCT00822887 | Completed Phase 1 DMC

• 1 other identifier: 06-0870.cc
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Gliomas

Keywords

malignant; gliomas

Outcome Measures

Primary Outcomes (1)

• Incidence of acute and delayed ≥ grade 3 Central nervous system (CNS) toxicity by Common Terminology Criteria (CTC) v.3.

  12 months.

Secondary Outcomes (5)

• Incidence of acute and delayed ≥ grade 3 non-CNS toxicity

  12 months.

• Progression-free survival at 6 months

  12 months.

• Overall survival

  12 months.

• Objective response rate

  12 months.

• Quality of survival

  12 months.

Study Arms (1)

Vandetanib

EXPERIMENTAL

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; Radiation: Fractionated Stereotactic Radiotherapy

Interventions

Vandetanib DRUG

Dose level 1:100 mg qd Dose level 2:200 mg qd Dose level 3:300 mg qd

Also known as: ZD6474, Zactima

Vandetanib

Fractionated Stereotactic Radiotherapy RADIATION

All patients will receive 36 Gy of radiation in three fractions, given in three consecutive days.

Vandetanib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Colorado Health Science Center

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Fields EC, Damek D, Gaspar LE, Liu AK, Kavanagh BD, Waziri A, Lillehei K, Chen C. Phase I dose escalation trial of vandetanib with fractionated radiosurgery in patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):51-7. doi: 10.1016/j.ijrobp.2010.09.008. Epub 2010 Oct 29.

  PMID: 21035955 DERIVED

MeSH Terms

Conditions

Glioma

Interventions

vandetanib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Changhu Chen, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2009
• First Posted: January 15, 2009
• Study Start: March 1, 2007
• Primary Completion: May 1, 2010
• Study Completion: January 1, 2011
• Last Updated: June 26, 2013

Record last verified: 2013-06

Locations

US (1)