Stereotactic Radiosurgery With Sunitinib for Brain Metastases

• Register: ClinicalTrials.gov
• Last refreshed on: 7 January 2013
• Main ID: NCT00981890
• Date of registration: 21/09/2009
• Primary sponsor: University Health Network, Toronto
• Public title: Stereotactic Radiosurgery With Sunitinib for Brain Metastases
• Scientific title: A Phase I Study of Stereotactic Radiosurgery Concurrent With Sunitinib in Patients With Brain Metastases
• Date of first enrolment: July 2009
• Target sample size: 22
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT00981890
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Canada

Contacts

• Name: Cynthia Menard, MD

• Name: Cynthia Menard, MD

• Name: Cynthia Menard, MD
• Affiliation: University Health Network, Princess Margaret Hospital

Key inclusion & exclusion criteria

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
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.

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
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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Brain Metastases

Intervention(s)

Drug: Sunitinib

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

Secondary ID(s)

UHN REB 09-0115-C

Source(s) of Monetary Support

Please refer to primary and secondary sponsors