Brain MetastasesPhase 1NCT00981890
Stereotactic Radiosurgery With Sunitinib for Brain Metastases
A Phase 1 study testing Sunitinib in people with Brain Metastases, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
The purpose of this study is to determine the maximum dose of sunitinib that can be tolerated when treatment is combined with radiotherapy. Patients who decide to take part in the study will start taking sunitinib alone for 7 days. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- Sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2009to May 2022
- 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
- Biopsy proven malignancy (original biopsy is adequate as long as the brain imaging is consistent with brain metastases).
- Patients age 18 years of age or older, as the effects of Sunitinib at the recommended therapeutic dose are unknown in children.
- A contrast-enhanced MRI demonstrating the presence of 1-3 brain metastases performed within four weeks prior to registration.
- The dominant contrast-enhancing intraparenchymal brain metastases must be well-circumscribed and must have a maximal diameter of ≤ 4.0 cm in any direction on the enhanced scan. If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0cm in maximum diameter.
- Life expectancy > 3 months
- RPA Class 1 and RPA Class 2 patients with stable primary disease
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- No systemic anti-cancer therapy within 30 days of starting or completing study treatment
- Patients must have normal organ and marrow function as defined in the protocol.
- Effects of Sunitinib on the developing human fetus at the recommended therapeutic dose are unknown. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients with leptomeningeal metastases documented by MRI or CSF evaluation
- Evidence of intratumoural or peritumoural hemorrhage deemed significant by the treating physician
- Patients with metastases within 5 mm of the optic chiasm or optic nerve
- Patients with metastases in the brainstem (midbrain, pons, or medulla).
- < 4 weeks since any major surgery. (Previous brain surgery, including craniotomy for tumour resection [except cerebral metastases] or biopsy is permissible.)
- Prior resection of cerebral metastasis
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- Previous cranial radiation. Patients may have had radiation therapy to other anatomical sites, but must have recovered from acute toxic effects prior to registration. At least 2 weeks must have elapsed since last dose of radiation before registration.
- Treatment with a non-approved or investigational drug concurrently or within 30 days before Day 0 of study treatment or within 30 days after the last day of study treatment.
- Treatment with sunitinib or other inhibitors of the VEGF signalling axis within 30 days before Day ) of study treatment or within 30 days after last day of study treatment.
- Bleeding disorders.
- Thrombolytic therapy within 4 weeks
- Concurrent use of anticoagulant or antiplatelet drugs
- Concurrent use of enzyme-inducing anti-epileptic drugs
- Patients with any condition that impairs their ability to swallow Sunitinib (e.g. gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with poorly controlled hypertension (systolic blood pressure of 150 mmHg or higher, or diastolic blood pressure of 100 mmHg or higher) are ineligible
- New York Heart Association (NYHA) Class III or IV disease
- NYHA class II disease controlled with treatment and monitoring allowed
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Sunitinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Pregnant women. These patients are excluded because there is an unknown but potential risk for adverse events in the fetus. Because there is also an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Sunitinib. Breastfeeding should be discontinued if the mother is treated with Sunitinib.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Sunitinib.
- Individuals with MRI non-compatible metal in the body, or unable to undergo MRI procedures.
- Allergy to gadolinium
- Allergy to Iodine Contrast Agent
- Glomerular Filtration Rate of less than 30ml.min/1.73m2 as measured by creatinine clearance through the Cockcroft-Gault formula [(140-age) X Mass in kg / 72 X plasma creatinine (mg/dl)]
- Primary germ cell tumor, small cell carcinoma, or lymphoma
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Health Network, Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase I Study of Stereotactic Radiosurgery Concurrent With Sunitinib in Patients With Brain Metastases
The purpose of this study is to determine the maximum dose of sunitinib that can be tolerated when treatment is combined with radiotherapy. Patients who decide to take part in the study will start taking sunitinib alone for 7 days. On the seventh day of taking sunitinib, patients will be given stereotactic radiosurgery (SRS).
The dose of radiation that patients will receive when they are given SRS is a standard dose used to help shrink brain metastases. The dose of radiation and the way it is delivered is not experimental.
Patients will then continue to take sunitinib seven days per week after SRS, and depending on how far along the study is when they join, they may continue taking the drug for up to 13 weeks after SRS. Patients will undergo weekly assessment during study treatment.
Read the detailed description
Brain metastases occur in 20% to 40% of all patients with cancer, with an incidence 10 times higher than that of primary malignant brain tumours. The reported median survival of patients with brain metastases is only 1-2 months with corticosteroids and 5-7 months with whole brain radiotherapy (WBRT). But with improvements in neuroimaging, brain metastases are being diagnosed more frequently and with a lower burden of disease, such that approximately 50-60% of patients have 1 to 4 brain metastases at diagnosis. In these patients, stereotactic radiosurgery (SRS), a single high dose of radiation delivered with high precision to the target lesion, is being used increasingly as an alternative to surgical resection or as an adjunct to WBRT. The addition of SRS to WBRT has provided improvements in local control and functional autonomy for patients with oligometastatic brain disease, supporting the hypothesis that SRS increases efficacy against tumours resistant to the significantly lower doses used in WBRT.
SRS can accomplish destruction of a defined intracranial target through precise targeting of a high dose of radiation with a sharp dose fall off at the target boundaries and minimal damage to surrounding tissue. Brain metastases are well suited for SRS as they are often small, radiographically well-circumscribed, pseudo-spherical tumors that are non-infiltrative, and they are often located at the gray-white junction, where toxicity to critical structures is minimal. SRS toxicity is low (<5%).
- Conditions
- Brain Metastases
- Being tested
- Sunitinib
- Keywords
- Brain Metastases, Stereotactic radiosurgery, Sunitinib, Patients with Brain Metastases
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Sunitinib is a tablet that is taken by mouth every day. Patients will be treated with Sunitinib alone for 7 days. On the seventh day of taking the drug they will be given SRS. Sunitinib will continue for seven days per week after SRS, and depending on how far along the study is when patients join, they may continue taking the drug for up to 13 weeks after SRS.
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Experimental | Not described Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety and maximum tolerated dose of Sunitinib when combined concurrently with SRS in patients with 1-3 brain metastases
Measured: 2 years
Secondary outcomes (1)
Assess: late toxicities/Tx effect on cognitive function/potential prognostic factors/time to Intracranial Local & Distant Progression/brain Progression-free Survival/alterations in tumour perfusion parameters & effects in normal brain tissue
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2009 (estimated)
- Study startJul 2009
- Primary completionMay 2014
- Study completionMay 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Caroline Chung, MD, Principal investigator, University Health Network, Princess Margaret Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00981890
- Sponsor's protocol ID
- UHN REB 09-0115-C
- Status last verified
- Oct 2022
- First submitted
- 21 Sep 2009
- Last updated
- 7 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Stereotactic Radiosurgery Concurrent With Sunitinib in Patients With Brain Metastases
- ClinicalTrials.gov ID
- NCT00981890
- Acronym / sponsor ID
- UHN REB 09-0115-C
- Conditions
- Brain Metastases
- Keywords
- Brain Metastases, Stereotactic radiosurgery, Sunitinib, Patients with Brain Metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jul 2009
- Primary completion
- May 2014 (actual)
- Study completion
- May 2022 (actual)
- First posted
- 22 Sep 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 this study is to determine the maximum dose of sunitinib that can be tolerated when treatment is combined with radiotherapy. Patients who decide to take part in the study will start taking sunitinib alone for 7 days. On the seventh day of taking sunitinib, patients will be given stereotactic radiosurgery (SRS).
The dose of radiation that patients will receive when they are given SRS is a standard dose used to help shrink brain metastases. The dose of radiation and the way it is delivered is not experimental.
Patients will then continue to take sunitinib seven days per week after SRS, and depending on how far along the study is when they join, they may continue taking the drug for up to 13 weeks after SRS. Patients will undergo weekly assessment during study treatment.
Detailed description
Brain metastases occur in 20% to 40% of all patients with cancer, with an incidence 10 times higher than that of primary malignant brain tumours. The reported median survival of patients with brain metastases is only 1-2 months with corticosteroids and 5-7 months with whole brain radiotherapy (WBRT). But with improvements in neuroimaging, brain metastases are being diagnosed more frequently and with a lower burden of disease, such that approximately 50-60% of patients have 1 to 4 brain metastases at diagnosis. In these patients, stereotactic radiosurgery (SRS), a single high dose of radiation delivered with high precision to the target lesion, is being used increasingly as an alternative to surgical resection or as an adjunct to WBRT. The addition of SRS to WBRT has provided improvements in local control and functional autonomy for patients with oligometastatic brain disease, supporting the hypothesis that SRS increases efficacy against tumours resistant to the significantly lower doses used in WBRT.
SRS can accomplish destruction of a defined intracranial target through precise targeting of a high dose of radiation with a sharp dose fall off at the target boundaries and minimal damage to surrounding tissue. Brain metastases are well suited for SRS as they are often small, radiographically well-circumscribed, pseudo-spherical tumors that are non-infiltrative, and they are often located at the gray-white junction, where toxicity to critical structures is minimal. SRS toxicity is low (<5%).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Experimental | Drug: Sunitinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Biopsy proven malignancy (original biopsy is adequate as long as the brain imaging is consistent with brain metastases).
- Patients age 18 years of age or older, as the effects of Sunitinib at the recommended therapeutic dose are unknown in children.
- A contrast-enhanced MRI demonstrating the presence of 1-3 brain metastases performed within four weeks prior to registration.
- The dominant contrast-enhancing intraparenchymal brain metastases must be well-circumscribed and must have a maximal diameter of ≤ 4.0 cm in any direction on the enhanced scan. If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0cm in maximum diameter.
- Life expectancy > 3 months
Key exclusion criteria (26 listed)
- Patients with leptomeningeal metastases documented by MRI or CSF evaluation
- Evidence of intratumoural or peritumoural hemorrhage deemed significant by the treating physician
- Patients with metastases within 5 mm of the optic chiasm or optic nerve
- Patients with metastases in the brainstem (midbrain, pons, or medulla).
- < 4 weeks since any major surgery. (Previous brain surgery, including craniotomy for tumour resection [except cerebral metastases] or biopsy is permissible.)
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 |
|---|---|---|
| SunitinibSunitinib is a tablet that is taken by mouth every day. Patients will be treated with Sunitinib alone for 7 days. On the seventh day of taking the drug they will be given SRS. Sunitinib will continue for seven days per week after SRS, and depending on how far along the study is when patients join, they may continue taking the drug for up to 13 weeks after SRS. | Drug | Sunitinib |
Primary outcome
Determine the safety and maximum tolerated dose of Sunitinib when combined concurrently with SRS in patients with 1-3 brain metastases
Time frame: 2 years
1 secondary outcome
Assess: late toxicities/Tx effect on cognitive function/potential prognostic factors/time to Intracranial Local & Distant Progression/brain Progression-free Survival/alterations in tumour perfusion parameters & effects in normal brain tissue
Time frame: 2 years
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 7 Oct 2022.
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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.
Caroline Chung, MD principal investigator
University Health Network, Princess Margaret Hospital
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 Sunitinib in people with Brain Metastases, run by University Health Network, Toronto at 1 site in Canada.
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 26 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 7 Oct 2022. 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 Canada. 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?
Determine the safety and maximum tolerated dose of Sunitinib when combined concurrently with SRS in patients with 1-3 brain metastases (time frame: 2 years). 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 7 Oct 2022.