A Pilot Study of GRN1005 for Resectable Brain Metastases in Patients With Breast Cancer and Non-Small Cell Lung Cancer
Brain metastasis is the most common intra-cranial tumor in adults with approximately 170,000
new cases being diagnosed in the United States annually. The incidence of brain metastasis
is increasing. Usually brain metastases of breast cancer occur after the diagnosis of
systemic metastases; but approximately 10-25% of patients with lung cancer have brain
metastases at diagnosis and another 40-50% develop them during the course of their disease.
Multiple factors are contributing to this increase: aging population, improved imaging
techniques, and improvement in the treatment of tumors leading to prolonged survival,
thereby allowing the emergence of brain metastases, with the brain being generally regarded
as a sanctuary site because of the blood- brain barrier (BBB). Lung cancer and breast cancer
are the leading tumor types, accounting for approximately 50% and 15 - 20% of patients with
This study will evaluate the ability of 18F-FLT to determine if amount of change in the
uptake in the brain metastases from breast and lung cancer after one dose of therapy with
GRN1005, correlates with intra-cranial response. FLT-PET utilizes a radiolabeled form of
thymidine, which is incorporated into DNA in proliferating cells. 18F-FLT uptake correlates
better than 18F-FDG with proliferation, tumor progression, and survival. Because CNS uptake
of FLT is low in contrast to FDG, this makes it potentially useful in evaluating CNS
metastases. We would like to see which of these imaging modalities is superior in detection
of brain metastases, and monitoring response to therapy.
-Determine whether one cycle of therapy GRN1005 is associated with a change in FLTPET
- Adult patients (greater than or equal to 18 years)
- Histologically or cytologically-documented breast cancer (HER2 status must be known) or
- Presence of resectable brain metastases based on evaluation by neurosurgery.
- At least one radiologically-confirmed and measurable metastatic brain lesion.
- Pilot non-randomized trial with or without trastuzumab
- Ten patients with resectable brain metastases from breast cancer and ten patients with
resectable brain metastases from NSCLC will be studied.
- Baseline imaging (brain tumor protocol MRI and DSC-PWI MRI, FLT-PET) 1-14 days prior to
first dose of GRN1005.
- Patients will receive 1 dose of GRN1005 on day 1 of study.
- Repeat FLT-PET imaging and MRIs will be done after 1 cycle of therapy and prior to
surgery, on day 21.
- On the day of surgery, patients will receive a second dose of GRN1005 3 to 6 hours
prior to brain surgery.
- PK studies will be done after each dose of GRN1005.
- Optional extra-cranial tumor biopsies will be performed before and after GRN1005
- Following surgery radiation therapy will be offered to patients as clinically indicated
per radiation oncologist's recommendation.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in FLT-PET uptake after one cycle of GRN1005
Susan E Bates, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|