GRN1005 for Brain Metastases From Breast or Lung Cancer
- Brain metastases are cancer cells that have spread to the brain from primary cancers in other organs. These tumors can be removed surgically. However, researchers are trying to find better ways to treat brain metastases. A new drug, GRN1005, has been designed to cross into the brain and deliver the cancer treatment drug paclitaxel to treat tumors. Researchers want to see how well GRN1005 works on brain metastases from breast or lung cancer.
- To test the safety and effectiveness of GRN1005 in treating brain metastases from breast or lung cancer.
- Individuals at least 18 years of age who have breast or lung cancer that has spread to the brain.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor tissue samples may also be collected. Imaging studies will also be performed.
- Participants who have breast cancer will be divided into two groups. Those whose cancer contains the HER2 protein will be treated with the drug Herceptin as well as GRN1005. Those without HER2 will have only GRN1005.
- Participants who have lung cancer will also have only GRN1005.
- All participants will have two doses of GRN1005, each 3 weeks apart. On the day the second dose of GRN1005 is given, participants will undergo surgery to remove the brain tumors.
- Treatment will be monitored with frequent blood tests and imaging studies.
Drug: GRN 1005
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of GRN1005 for Resectable Brain Metastases in Patients With Breast Cancer and Non-Small Cell Lung Cancer|
- Change in FLT-PET uptake after one cycle of GRN1005 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Determine whether presence of markers of stable tubulin (glu-terminated and acetylated tubulin) and PARP cleavage in tumor and the isotype expression are associated with 3-week intracranial tumor response.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
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 brain metastases.
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 uptake.
- Adult patients (greater than or equal to 18 years)
- Histologically or cytologically-documented breast cancer (HER2 status must be known) or NSCLC
- 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 administration.
- Following surgery radiation therapy will be offered to patients as clinically indicated per radiation oncologist s recommendation.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Susan E Bates, M.D.||National Cancer Institute (NCI)|