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A Phase I Study of Stereotactic Radiosurgery Concurrent With Sunitinib in Patients With Brain Metastases

Phase 1
18 Years
Open (Enrolling)
Brain Metastases

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Trial Information

A Phase I Study of Stereotactic Radiosurgery Concurrent With Sunitinib in Patients With Brain Metastases

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%).

Inclusion Criteria:

- 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

- No systemic anti-cancer therapy within 30 days of starting or completing study

- 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

Exclusion Criteria:

- 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

- 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

- 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 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the safety and maximum tolerated dose of Sunitinib when combined concurrently with SRS in patients with 1-3 brain metastases

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Caroline Chung, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network, Princess Margaret Hospital


Canada: Ethics Review Committee

Study ID:

UHN REB 09-0115-C



Start Date:

July 2009

Completion Date:

July 2014

Related Keywords:

  • Brain Metastases
  • Brain Metastases
  • Stereotactic radiosurgery
  • Sunitinib
  • Patients with Brain Metastases
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Brain Neoplasms