18F-FLT-PET Imaging of the Brain in Patients With Metastatic Breast Cancer to the Brain Treated With Whole Brain Radiation Therapy With or Without Sorafenib: Comparison With MR Imaging of the Brain

Study Overview
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Brief Summary
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The purpose of this study is to compare two different imaging methods to examine the response of brain metastases to WBRT. These two imaging methods will take pictures of the brain using : 1) a positron emission tomography (PET) scanner and 2) Magnetic Resonance Imaging (MRI) scanner. A PET scanner resembles a CT or MR scanner.PET scans use radioactive substances also called as radioactive markers to see cancer cells. We plan to use [18F]FLT as a radioactive marker. FLT is used to image tumor growth. FLT PET scan is a new clinical procedure. It is in the testing stage of development unlike FDG-PET which is used more commonly used. Therefore, this is considered a research study. This will help us evaluate whether this scan will be safe and better used in the future to evaluate tumors. The amount of radiation to the body is small. The radiation from the radiotracer drug will be gone from the body in a few hours. There is no radiation risk from the MRI scans. Additionally, we also plan to use MRI imaging of the brain. We expect that [18F]FLT PET is better when compared to MRI and will give us more information about the brain metastases after WBRT.

Official Title
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Pilot Study of 18F-FLT-PET Imaging of the Brain in Patients With Metastatic Breast Cancer to the Brain Treated With Whole Brain Radiation Therapy With or Without Sorafenib: Comparison With MR Imaging of the Brain

Conditions
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Metastatic Breast Cancer to the Brain

Intervention / Treatment
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* Device: 18F-FLT-PET Imaging
* Device: 18F-FLT-PET Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed (confirmation done at MSKCC) metastatic adenocarcinoma of the breast Radiologic evidence of new and/or progressive brain metastases ((≥10 mm in longest dimension) by MRI imaging of the Brain Planned WBRT based on number (≥ 3 lesions) and/or size (≥ 1 cm) of brain metastases. Age ≥18 years; males and females Patients who require additional clinically indicated stereotactic radiosurgery (SRS) in addition to WBRT will also be eligible. Life expectancy of >12 weeks. Karnofsky Performance Status (KPS) ≥ 70%. Creatinine ≤2.0 times the upper limit of normal. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to enrollment, must be non-lactating and must agree to use adequate contraception prior to enrollment and for the duration of study participation. No limit to prior therapies with last anti-cancer treatment ≥2 weeks from initiation of WBRT. Please note: there is no washout period required for trastuzumab, pertuzumab, for patients who have developed new parenchymal brain metastases while on these agents. Exclusion Criteria: Leptomeningeal metastases Please note: leptomeningeal metastases may be allowed if it is limited to cranial metastasis (MRI spine should be completed, within 4 weeks of enrollment, to show that no other leptomeningeal metastases is present) and is not the only metastasis present in the brain. Concurrent administration of lapatinib or other tyrosine kinase inhibitors other than sorafenib Craniotomy or any other major surgery, open biopsy, or significant traumatic injury within 4 weeks of randomization. Concurrent anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than sorafenib, and protocol-specified whole-brain radiotherapy. Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, preceding enrollment. Inability to comply with protocol and /or not willing or not available for follow-up assessments. Any condition which in the investigator's opinion makes the patient unsuitable for the study participation. Patient is incontinent of urine or stool (which would make them unable to tolerate lying still for 60 minutes). Claustrophobia Known allergic reaction to Gd-DTPA Renal insufficiency with recent (<3 month old) creatinine >2.0

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1 will include the first ten patients treated with WBRT concomitantly with sorafenib (on a separate phase I trial). We will perform a pilot study of serial FLT-PET imaging of the brain at baseline (< 4 weeks prior to initiation of WBRT), up to 7-10 days post-WBRT and 10-12 weeks after WBRT in patients with metastatic breast cancer to the brain (N=20) treated with WBRT with or without sorafenib. | Device: 18F-FLT-PET Imaging<br>* All patients will be imaged using FLT-PET scans at baseline (within 4 weeks of initiation of WBRT), 7-10 days after completion of WBRT and then 10-12 weeks after WBRT. Patients will also be evaluated with MRI imaging at baseline and then 10-12 weeks after WBRT. Patients will be followed with MRI every 3 months (+/- 7 days) for the first year and then every 6 months (+/- 7 days) thereafter which is the standard of care.<br>|
| Experimental: Cohort 2<br>Cohort 2 will include patients treated with standard WBRT alone. Patients in both these cohorts will also be assessed with standard non-invasive MRI in addition to [18F] FLT PET at baseline (< 4 weeks of WBRT) and 10-12 weeks after completion of WBRT. | Device: 18F-FLT-PET Imaging<br>* All patients will be imaged using FLT-PET scans at baseline (within 4 weeks of initiation of WBRT), 7-10 days after completion of WBRT and then 10-12 weeks after WBRT. Patients will also be evaluated with MRI imaging at baseline and then 10-12 weeks after WBRT. Patients will be followed with MRI every 3 months (+/- 7 days) for the first year and then every 6 months (+/- 7 days) thereafter which is the standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall Response Rate is the proportion of participants who had a complete or partial response (Cohort 1) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Avg SUV Max From Baseline to 1 Year | Comparing FLT PET findings with tissue analysis will enable us to determine if imaging results are concordant with histological findings and thus allow for confirmation of this hypothesis. In this manner, we propose to generate a bridge between tissue analysis and FLT-PET brain imaging studies. For patients needing to undergo craniotomy for resection of a brain metastasis after WBRT, tissue findings (radionecrosis versus viable tumor) will be correlated with radiologic assessment in an exploratory manner. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast, brain metastases, 18F-FLT-PET Imaging, FLT(3'DEOXY-3'FLUOROTHYMIDINE), MR Imaging, 12-039