Metastatic Breast Cancer to the Brain
Conditions
Keywords
Breast, brain metastases, 18F-FLT-PET Imaging, FLT(3'DEOXY-3'FLUOROTHYMIDINE), MR Imaging, 12-039
Brief summary
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.
Interventions
DEVICE18F-FLT-PET Imaging
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.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 1 year | Overall Response Rate is the proportion of participants who had a complete or partial response (Cohort 1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Avg SUV Max From Baseline to 1 Year | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 All participants 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.
Participants will also be evaluated with MRI imaging at baseline and then 10-12 weeks after WBRT.
Participants 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. | 12 |
| Cohort 2 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. | 5 |
| Total | 17 |
Baseline characteristics
| Characteristic | Cohort 1 | Total | Cohort 2 |
|---|---|---|---|
| Age, Continuous | 58 years | 53 years | 53 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 13 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 12 Participants | 4 Participants |
| Region of Enrollment United States | 12 Participants | 17 Participants | 5 Participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 12 | 5 / 5 |
| other Total, other adverse events | 0 / 12 | 0 / 5 |
| serious Total, serious adverse events | 0 / 12 | 4 / 5 |
Outcome results
Primary
Overall Response Rate
Overall Response Rate is the proportion of participants who had a complete or partial response (Cohort 1)
Time frame: 1 year
Population: 12-039 is a companion FLT-PET brain imaging study to 12-046.~10 participants from 12-046 were consented to 12-039. 10 other participants were approached for FLT-PET brain imaging getting standard WBRT off of 12-046, (without sorafenib), as a comparator group (not arm).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Metastatic Breast Cancer | Overall Response Rate | 71 % of pts w/complete or partial response |
Secondary
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.
Time frame: 1 year
Population: 12-039 is a companion FLT-PET brain imaging study to 12-046.~10 participants from 12-046 were consented to 12-039. 10 other participants were approached for FLT-PET brain imaging getting standard WBRT off of 12-046, (without sorafenib), as a comparator group (not arm).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Metastatic Breast Cancer | Change in Avg SUV Max From Baseline to 1 Year | Decline in avg SUV max of >/= 25% of WBRT + sorafenib participants | 9 participants |
| Participants With Metastatic Breast Cancer | Change in Avg SUV Max From Baseline to 1 Year | Decline in avg SUV max of >/= 25% of WBRT participants | 0 participants |
| Participants With Metastatic Breast Cancer | Change in Avg SUV Max From Baseline to 1 Year | No decline in avg SUV max of >/= 25% of WBRT + sorafenib participants | 1 participants |
| Participants With Metastatic Breast Cancer | Change in Avg SUV Max From Baseline to 1 Year | No decline in avg SUV max of >/= 25% of WBRT participants | 0 participants |
| Participants With Metastatic Breast Cancer | Change in Avg SUV Max From Baseline to 1 Year | Not enrolled in FLT-PET study | 2 participants |
| Cohort 2 | Change in Avg SUV Max From Baseline to 1 Year | No decline in avg SUV max of >/= 25% of WBRT participants | 3 participants |
| Cohort 2 | Change in Avg SUV Max From Baseline to 1 Year | Not enrolled in FLT-PET study | 0 participants |
| Cohort 2 | Change in Avg SUV Max From Baseline to 1 Year | Decline in avg SUV max of >/= 25% of WBRT + sorafenib participants | 0 participants |
| Cohort 2 | Change in Avg SUV Max From Baseline to 1 Year | No decline in avg SUV max of >/= 25% of WBRT + sorafenib participants | 0 participants |
| Cohort 2 | Change in Avg SUV Max From Baseline to 1 Year | Decline in avg SUV max of >/= 25% of WBRT participants | 2 participants |