GliosarcomaPhase 1NCT00613223
Ph I Dose Escalation Trial of Vandetanib in Combo w Etoposide for Malignant Gliomas
A Phase 1 study testing Vandetanib and Etoposide in people with Gliosarcoma and Glioblastoma, run by Annick Desjardins at 1 site in United States.
Trial summary
Primary Objective: To determine maximum tolerated dose \& dose limiting toxicity of vandetanib when combined with standard dosing of etoposide among patients with recurrent malignant glioma who are on \& not on enzyme-inducing anti-epileptic drugs (EIAEDs) Secondary Objectives: To assess safety \& tolerability of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gliosarcoma, Glioblastoma
- What is being tested?
- Vandetanib and Etoposide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to May 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients have baseline evaluations ≤14days prior to 1st dose of study drug unless otherwise specified
- Patients with confirmed malignant glioma (MG) who are recurrence/relapse
- Patients may not have stereotactic tumor biopsy < 1 week or surgical resection or open biopsy < 4 weeks before starting study drug
- For stratum of non-EIAED patients, each patient must be off all EIAEDs for > 2 weeks prior to starting study drug; similarly for stratum of EIAED patients, each patient must be on EIAED for >2 weeks prior to starting study drug
- Patients should be on non-increasing dose of steroids for >7 days prior to obtaining baseline MRI with gadolinium (Gd-MRI) of brain
- Patients should be on non-increasing dose of steroids for >7 days prior to starting study drug
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- Multifocal disease is eligible
- Age ≥ 18 years
- Karnofsky Performance Status (KPS) ≥70
- Absolute Neutrophil Count ≥1.0 x 10 9/L
- Hemoglobin (Hgb) ≥9 g/dL
- Platelets ≥100 x 10 9/L
- Serum creatinine ≤1.5 x ULRR or measured 24-hr CrCl ≥50mL/min/1.73m2
- Life expectancy ≥ 12 weeks
- Written informed consent obtained prior to screening procedures
- Negative Beta-HCG pregnancy test for women of child-bearing potential
Who cannot join
- Laboratory Results:
- Serum direct bilirubin >1.5 x upper limit of normal (ULN) of reference range
- Serum creatinine >1.5 x ULRR \& CrCl <30 mL/min
- Potassium, <4.0 mmol/L despite supplementation; serum calcium, magnesium out of normal range despite supplementation
- ALT or AST > 2.5 x ULRR
- Evidence of severe/uncontrolled systemic disease or any concurrent condition which in Investigator's opinion makes it undesirable for patient to participate in trial or which would jeopardize compliance with protocol
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- Clinically significant cardiovascular event such as myocardial infarction, superior vena cava syndrome, New York Heart Association classification of heart disease >2 within 3 months before entry; or presence of cardiac disease that, in opinion of Investigator, increases risk of ventricular arrhythmia
- History of arrhythmia which is symptomatic/requires treatment/asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
- Previous history of QTc prolongation as result from other medication that required discontinuation of that medication
- Congenital long QT syndrome, or 1st degree relative with unexplained sudden death <40 years
- Presence of left bundle branch block
- QTc with Bazett's correction that's unmeasureable, or ≥ 480msec on screening EEG.
- Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes/induce CYP3A4 function except for EIAEDs
- Hypertension not controlled by medical therapy
- Currently active diarrhea that may affect ability of patient to absorb study regimen/tolerate diarrhea
- Women who are currently pregnant/breast feeding
- Previous or current malignancies of other histologies the last year, with exception of cervical carcinoma in situ \& adequately treated basal cell or squamous cell carcinoma of skin
- Receipt of any investigational agents <30 days prior to commencing study treatment unless pt has recovered from all anticipated toxicities of investigational agent
- Last dose of prior chemo discontinued < 4 weeks before start of study therapy unless pt has recovered from all anticipated toxicities of chemo
- Last XRT < 4 weeks before start of study therapy, unless patient has recovered from all anticipated toxicities of XRT
- Any unresolved toxicity >CTC gr1 from previous anti-cancer therapy
- Previous enrollment/randomization of treatment in present study
- Major surgery < 4 weeks/incompletely healed surgical incision before starting study therapy
- Patients who have received prior oral VEGFR, EGFR or PDGFR-directed therapies. Patients who received prior Avastin will be eligible as long as at least 6 weeks has elapsed since last dose.
- Patients taking warfarin sodium
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health System
Durham, North Carolina, 27710
About this study
Official title: Phase I Dose Escalation of Vandetanib (Zactima, ZD6474) in Combination With Etoposide for Malignant Gliomas
Primary Objective: To determine maximum tolerated dose \& dose limiting toxicity of vandetanib when combined with standard dosing of etoposide among patients with recurrent malignant glioma who are on \& not on enzyme-inducing anti-epileptic drugs (EIAEDs) Secondary Objectives: To assess safety \& tolerability of vandetanib + etoposide in this population; To evaluate pharmacokinetics of vandetanib among malignant glioma patients on \& not on EIAEDs when combined with etoposide.
Exploratory Objective: To evaluate for evidence of anti-tumor activity of study regimen among recurrent malignant glioma patients including radiographic response rate, 6-month progression free survival (PFS) rate \& median PFS.
Read the detailed description
This is open-label, single center, 2-cohort phase I dose-escalation study of vandetanib administered orally on continuous daily dosing schedule + oral etoposide among adult patients with recurrent or relapsing malignant glioma. Patients will be stratified based on whether they are receiving EIAEDs \& each stratum will independently dose escalate. Dose of vandetanib will be increased in successive cohorts of patients. Etoposide will be given daily at a dose of 50mg/day for 21 days followed by 7 days with no etoposide. Cohorts of 3-6 subjects will accrue at each dose level until maximum tolerated dose (MTD) is defined. Subjects will be adult patients with histologically confirmed malignant glioma who are presenting at time of recurrence/relapse. Up to 48 subjects will be enrolled.
Sample size will be based on modified, classical "3+3" dose escalation design. Primary safety \& efficacy analysis will be conducted on all subject data at time all subjects who are still receiving study drug will have completed at least 4 cycles of treatment. Most common adverse events (AEs) associated with vandetanib are rash, diarrhea, \& asymptomatic QTc prolongation. Protracted oral dosing of etoposide is associated with toxicity that is mild in most patients \& consists mainly of myelosuppression \& diarrhea. Less commonly, protracted etoposide dosing has been associated w more significant hematologic toxicity.
- Conditions
- Gliosarcoma, Glioblastoma
- Being tested
- Vandetanib and Etoposide
- Keywords
- Malignant Gliomas, Etopophos, Toposar, VePesid, Etoposide, Vandetanib, Zactima, ZD6474, VP-16, Brain Tumor, Recurring Malignant Brain Tumor, Gliosarcoma, Glioblastoma, Glioma, Malignant Glioma, GBM
- Medical subject headings
- Gliosarcoma, Glioblastoma, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vandetanib and EtoposideDrug
Also called Vandetanib - Zactima (ZD 6474), Etoposide - VP-16, Etopophos, Toposar, VePesid
Vandetanib will be given orally once day. Swallow tablet with 240 ml of non-carbonated water. Initial dose is 100 mg/day for stratum 1 \& 200 mg/day for stratum 2. Etoposide will be taken by mouth in capsule form at a flat dose of 50 mg/day for 1st 21 days of 28-day cycle. You will not take etoposide for following 7 days of the cycle.
| Study group | Role | What they receive |
|---|---|---|
| Vandetanib and Etoposide | Experimental | Patients will be stratified based on whether they are receiving an enzyme-inducing anti-epileptic drug (EIAED). The dose level of vandetanib will be increased in successive cohorts of subjects. Etoposide will be given daily at a dose of 50 mg/ day for 21 days followed by 7 days with no etoposide. Receives: Drug: Vandetanib and Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, tolerability, biologic activity, & pharmacokinetic profile of vandetanib when used in combo w etoposide
Measured: 6-month progression free survival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionOct 2010
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Annick Desjardins
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Annick Desjardins, Duke University
- Investigators
- Annick Desjardins, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00613223
- Sponsor's protocol ID
- Pro00001919
- Status last verified
- Feb 2013
- First submitted
- 29 Jan 2008
- Last updated
- 20 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation of Vandetanib (Zactima, ZD6474) in Combination With Etoposide for Malignant Gliomas
- ClinicalTrials.gov ID
- NCT00613223
- Acronym / sponsor ID
- Pro00001919
- Conditions
- Gliosarcoma, Glioblastoma
- Keywords
- Malignant Gliomas, Etopophos, Toposar, VePesid, Etoposide, Vandetanib, Zactima, ZD6474
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Annick DesjardinsUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Feb 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 12 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective: To determine maximum tolerated dose \& dose limiting toxicity of vandetanib when combined with standard dosing of etoposide among patients with recurrent malignant glioma who are on \& not on enzyme-inducing anti-epileptic drugs (EIAEDs) Secondary Objectives: To assess safety \& tolerability of vandetanib + etoposide in this population; To evaluate pharmacokinetics of vandetanib among malignant glioma patients on \& not on EIAEDs when combined with etoposide.
Exploratory Objective: To evaluate for evidence of anti-tumor activity of study regimen among recurrent malignant glioma patients including radiographic response rate, 6-month progression free survival (PFS) rate \& median PFS.
Detailed description
This is open-label, single center, 2-cohort phase I dose-escalation study of vandetanib administered orally on continuous daily dosing schedule + oral etoposide among adult patients with recurrent or relapsing malignant glioma. Patients will be stratified based on whether they are receiving EIAEDs \& each stratum will independently dose escalate. Dose of vandetanib will be increased in successive cohorts of patients. Etoposide will be given daily at a dose of 50mg/day for 21 days followed by 7 days with no etoposide. Cohorts of 3-6 subjects will accrue at each dose level until maximum tolerated dose (MTD) is defined. Subjects will be adult patients with histologically confirmed malignant glioma who are presenting at time of recurrence/relapse. Up to 48 subjects will be enrolled.
Sample size will be based on modified, classical "3+3" dose escalation design. Primary safety \& efficacy analysis will be conducted on all subject data at time all subjects who are still receiving study drug will have completed at least 4 cycles of treatment. Most common adverse events (AEs) associated with vandetanib are rash, diarrhea, \& asymptomatic QTc prolongation. Protracted oral dosing of etoposide is associated with toxicity that is mild in most patients \& consists mainly of myelosuppression \& diarrhea. Less commonly, protracted etoposide dosing has been associated w more significant hematologic toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vandetanib and Etoposide | Experimental | Drug: Vandetanib and EtoposidePatients will be stratified based on whether they are receiving an enzyme-inducing anti-epileptic drug (EIAED). The dose level of vandetanib will be increased in successive cohorts of subjects. Etoposide will be given daily at a dose of 50 mg/ day for 21 days followed by 7 days with no etoposide. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients have baseline evaluations ≤14days prior to 1st dose of study drug unless otherwise specified
- Patients with confirmed malignant glioma (MG) who are recurrence/relapse
- Patients may not have stereotactic tumor biopsy < 1 week or surgical resection or open biopsy < 4 weeks before starting study drug
- For stratum of non-EIAED patients, each patient must be off all EIAEDs for > 2 weeks prior to starting study drug; similarly for stratum of EIAED patients, each patient must be on EIAED for >2 weeks prior to starting study drug
- Patients should be on non-increasing dose of steroids for >7 days prior to obtaining baseline MRI with gadolinium (Gd-MRI) of brain
Key exclusion criteria (25 listed)
- Laboratory Results:
- Serum direct bilirubin >1.5 x upper limit of normal (ULN) of reference range
- Serum creatinine >1.5 x ULRR \& CrCl <30 mL/min
- Potassium, <4.0 mmol/L despite supplementation; serum calcium, magnesium out of normal range despite supplementation
- ALT or AST > 2.5 x ULRR
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vandetanib and EtoposideAlso: Vandetanib - Zactima (ZD 6474), Etoposide - VP-16, Etopophos, Toposar, VePesidVandetanib will be given orally once day. Swallow tablet with 240 ml of non-carbonated water. Initial dose is 100 mg/day for stratum 1 \& 200 mg/day for stratum 2. Etoposide will be taken by mouth in capsule form at a flat dose of 50 mg/day for 1st 21 days of 28-day cycle. You will not take etoposide for following 7 days of the cycle. | Drug | Vandetanib and Etoposide |
Primary outcome
Safety, tolerability, biologic activity, & pharmacokinetic profile of vandetanib when used in combo w etoposide
Time frame: 6-month progression free survival
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2013.
- The Preston Robert Tisch Brain Tumor Center at DUKELink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annick Desjardins, MD principal investigator
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vandetanib and Etoposide in people with Gliosarcoma and Glioblastoma, run by Annick Desjardins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety, tolerability, biologic activity, & pharmacokinetic profile of vandetanib when used in combo w etoposide (time frame: 6-month progression free survival). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2013.