Malignant GliomasPhase 1IRUSZACT0073NCT00822887
Dose Escalation Study of Vandetanib With Hypofractionated Stereotactic Radiotherapy in Recurrent Malignant Gliomas
A Phase 1 study testing Vandetanib and Fractionated Stereotactic Radiotherapy in people with Malignant Gliomas, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Gliomas
- What is being tested?
- Vandetanib and Fractionated Stereotactic Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Jan 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 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
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- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Health Science Center
Aurora, Colorado, 80045
About this study
Official title: A Phase I Dose Escalation Study of Vandetanib (ZACTIMA, ZD6474) With Hypofractionated Stereotactic Radiotherapy in Patients With Recurrent Malignant Gliomas
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.
Read more
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.
Read the detailed description
Screening Prior to receiving any treatment, tests will be performed to determine overall medical condition. This will include blood tests, questions about medical history, and physical and neurological exams.
MRI scan of the brain, electrocardiogram (ECG) and chest X-ray will be performed as baseline studies if they have not been performed in the last 28 days.
Women of child-bearing potential will also have a serum pregnancy test within 2 days before taking the study drug.
During treatment If all of the study criteria are met and subject is enrolled in the study, you will start taking the study drug at least 7 days before radiation therapy. You will take the study drug once a day by mouth. You should take the study drug at about the same time each day. If you forget to take a dose, take the missed dose as soon as you remember, as long as it is at least 12 hours before the next dose is due. If it is less than 12 hours until the next dose, do not take the dose you have missed. If you throw up within 30 minutes after you take the study drug, you should take another dose, and use medicine to stop or relieve your vomiting per your doctor's instruction. You will continue to take the study drug for a total duration of one year. The study will be stopped if your disease progresses or there is excessive toxicity. Your participation in the study will be for one year. However, we will continue to follow your disease status, general health and possible treatment-related side effects after one year and for as long as possible.
This is a Phase I study. These types of studies usually include a small number of subjects and are often called dose-escalation studies. Subjects in the first dose group will be receiving a small dose of the study drug. If no unacceptable side effects are observed in these subjects, the next group of subjects will receive the next higher dose of study drug. The study drug doses planned are as follows:
Dose Level Drug dose Level 1 100 mg once a day Level 2 200 mg once a day Level 3 300 mg once a day
You will be assigned to one of three levels depending on when you enter the study.
You will also receive radiation therapy. The radiation dose is the same for all patients. Radiation therapy will begin at least 7 days after you begin taking the study drug. The radiation therapy will be once a day for 3 consecutive days. A special plastic mask will be made for you and used to hold your head still during each radiation treatment.
Tests and procedures will be performed throughout your treatment to determine how your cancer is responding and to monitor you for safety purposes. The tests and procedures will be scheduled for you. The following tests and procedures will be performed:
- Physical examination, neurological examination, and ECG, right before, and in the first, second, fourth, eighth and twelfth week of drug treatment; then once every three months.
- Brain MRI and quality of life questionnaires at one month and three month after radiation therapy, then once every three months.
- Chest X-ray as your doctor determines.
Follow-up You will also have follow-up visits with your doctor once a month for the first 6 months, then once every three months. You may also see your doctor anytime as needed.
Duration You will be on this study for up to 12 months.
- Conditions
- Malignant Gliomas
- Being tested
- Vandetanib, Fractionated Stereotactic Radiotherapy
- Keywords
- malignant, gliomas
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VandetanibDrug
Also called ZD6474, Zactima
Dose level 1:100 mg qd Dose level 2:200 mg qd Dose level 3:300 mg qd
Fractionated Stereotactic RadiotherapyRadiation
All patients will receive 36 Gy of radiation in three fractions, given in three consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Vandetanib; Radiation: Fractionated Stereotactic Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of acute and delayed ≥ grade 3 Central nervous system (CNS) toxicity by Common Terminology Criteria (CTC) v.3.
Measured: 12 months.
Secondary outcomes (5)
Incidence of acute and delayed ≥ grade 3 non-CNS toxicity
Measured: 12 months.
Progression-free survival at 6 months
Measured: 12 months.
Overall survival
Measured: 12 months.
Objective response rate
Measured: 12 months.
Quality of survival
Measured: 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2009 (estimated)
- Study startMar 2007
- Primary completionMay 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant GliomasStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Changhu Chen, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00822887
- Sponsor's protocol ID
- 06-0870.cc
- Acronym
- IRUSZACT0073
- Status last verified
- Jun 2013
- First submitted
- 13 Jan 2009
- Last updated
- 26 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 21035955
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of Vandetanib (ZACTIMA, ZD6474) With Hypofractionated Stereotactic Radiotherapy in Patients With Recurrent Malignant Gliomas
- ClinicalTrials.gov ID
- NCT00822887
- Acronym / sponsor ID
- IRUSZACT0073 / 06-0870.cc
- Conditions
- Malignant Gliomas
- Keywords
- malignant, gliomas
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Mar 2007
- Primary completion
- May 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 15 Jan 2009 (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.
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.
Detailed description
Screening Prior to receiving any treatment, tests will be performed to determine overall medical condition. This will include blood tests, questions about medical history, and physical and neurological exams.
MRI scan of the brain, electrocardiogram (ECG) and chest X-ray will be performed as baseline studies if they have not been performed in the last 28 days.
Women of child-bearing potential will also have a serum pregnancy test within 2 days before taking the study drug.
During treatment If all of the study criteria are met and subject is enrolled in the study, you will start taking the study drug at least 7 days before radiation therapy. You will take the study drug once a day by mouth. You should take the study drug at about the same time each day. If you forget to take a dose, take the missed dose as soon as you remember, as long as it is at least 12 hours before the next dose is due. If it is less than 12 hours until the next dose, do not take the dose you have missed. If you throw up within 30 minutes after you take the study drug, you should take another dose, and use medicine to stop or relieve your vomiting per your doctor's instruction. You will continue to take the study drug for a total duration of one year. The study will be stopped if your disease progresses or there is excessive toxicity. Your participation in the study will be for one year. However, we will continue to follow your disease status, general health and possible treatment-related side effects after one year and for as long as possible.
This is a Phase I study. These types of studies usually include a small number of subjects and are often called dose-escalation studies. Subjects in the first dose group will be receiving a small dose of the study drug. If no unacceptable side effects are observed in these subjects, the next group of subjects will receive the next higher dose of study drug. The study drug doses planned are as follows:
Dose Level Drug dose Level 1 100 mg once a day Level 2 200 mg once a day Level 3 300 mg once a day
You will be assigned to one of three levels depending on when you enter the study.
You will also receive radiation therapy. The radiation dose is the same for all patients. Radiation therapy will begin at least 7 days after you begin taking the study drug. The radiation therapy will be once a day for 3 consecutive days. A special plastic mask will be made for you and used to hold your head still during each radiation treatment.
Tests and procedures will be performed throughout your treatment to determine how your cancer is responding and to monitor you for safety purposes. The tests and procedures will be scheduled for you. The following tests and procedures will be performed:
- Physical examination, neurological examination, and ECG, right before, and in the first, second, fourth, eighth and twelfth week of drug treatment; then once every three months.
- Brain MRI and quality of life questionnaires at one month and three month after radiation therapy, then once every three months.
- Chest X-ray as your doctor determines.
Follow-up You will also have follow-up visits with your doctor once a month for the first 6 months, then once every three months. You may also see your doctor anytime as needed.
Duration You will be on this study for up to 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vandetanib | Experimental | Drug: Vandetanib, Radiation: Fractionated Stereotactic RadiotherapyDose 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (23 listed)
- 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)
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 |
|---|---|---|
| VandetanibAlso: ZD6474, ZactimaDose level 1:100 mg qd Dose level 2:200 mg qd Dose level 3:300 mg qd | Drug | Vandetanib |
| Fractionated Stereotactic RadiotherapyAll patients will receive 36 Gy of radiation in three fractions, given in three consecutive days. | Radiation | Vandetanib |
Primary outcome
Incidence of acute and delayed ≥ grade 3 Central nervous system (CNS) toxicity by Common Terminology Criteria (CTC) v.3.
Time frame: 12 months.
5 secondary outcomes
Incidence of acute and delayed ≥ grade 3 non-CNS toxicity
Time frame: 12 months.
Progression-free survival at 6 months
Time frame: 12 months.
Overall survival
Time frame: 12 months.
Objective response rate
Time frame: 12 months.
Quality of survival
Time frame: 12 months.
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 26 Jun 2013.
- Derived from this study: PubMed 21035955Fields 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.
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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.
Changhu Chen, MD principal investigator
University of Colorado, Denver
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 Fractionated Stereotactic Radiotherapy in people with Malignant Gliomas, run by University of Colorado, Denver 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 10 inclusion and 23 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 26 Jun 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?
Incidence of acute and delayed ≥ grade 3 Central nervous system (CNS) toxicity by Common Terminology Criteria (CTC) v.3. (time frame: 12 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00822887, which also lists 1 linked publication.
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 26 Jun 2013.