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Imaging With [11C]Martinostat in Breast Cancer

Primary Purpose

Breast Cancer

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

[11C]Martinostat

MR-PET scanner

About this trial

This is an interventional diagnostic trial for Breast Cancer focused on measuring Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Be at least 18 years or age (required for legal consent)
Have ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
Have breast imaging findings from mammogram, ultrasound, or breast MRI that are highly suspicious (i.e. coded as BI RADS 5) for breast cancer.
Have primary breast tumor that is at least 2 cm in diameter as measured in any dimension on either mammogram, ultrasound, or breast MRI
Have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

General Exclusion Criteria

Previously treated breast cancer
Concurrent malignancy of any type
Recent breast surgery (within the past 12 months) on the ipsilateral breast as the current breast tumor
Impaired elimination (as defined as having problems with urination)
Metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan
Participation in a research study/studies involving radiation exposure within the past 12 months
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, major kidney or liver disease, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnancy
Currently lactating (either breast feeding or breast pumping)
Pregnant women are excluded from this study because of the radioactivity of [11C]Martinostat and the resulting risks of teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to administration of [11C]Martinostat, and because lactation may potentially affect the uptake of [11C]Martinostat on PET, breastfeeding women are excluded from the study.

General MR and PET Safety Exclusion Criteria:

Electrical implants such as cardiac pacemakers or perfusion pumps
Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, steel implants, ferromagnetic objects such as jewelry or metal clips in clothing
Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions, and any greater than normal potential for cardiac arrest
Inability to lie comfortably on a bed inside a PET camera for 90 minutes as assessed by physical examination and medical history (e.g. back pain, arthritis)
Pregnancy: A negative serum pregnancy test is required on the day of the PET procedure for female subjects of child-bearing age.
Body weight of > 250 lbs (weight limit of the MRI table as well as risks to larger patients from MRI elements)

Sites / Locations

Massachusetts General Hospital Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

[11C]Martinostat

Arm Description

Subjects will be administered [11C]Martinostat, which is synthesized on site at the MGH Martinos Imaging Center All subjects will undergo an MR-PET scan of the thorax, including the breasts, to determine tumor uptake All subjects will be scanned using [11C]Martinostat during an imaging session on a Siemens Biograph mMR integrated MR-PET scanner PET imaging will begin concomitant with radiotracer administration

Outcomes

Primary Outcome Measures

PET-MRI Visualization and Quantification of Breast Tumor Uptake of [11C]Martinostat Above Background Uptake, as Assessed by SUV Measurements

Evaluate the ability of PET-MRI to visualize and quantify uptake of [11C]Martinostat in breast tumors above background tracer uptake. SUVmax will be collected from the primary breast tumor and the normal background breast tissue. The study is powered to detect a difference in mean background SUVmax of 0.4 in breast parenchyma uninvolved by tumor and breast parenchyma with breast tumor using a two-sample t-test.

Secondary Outcome Measures

Quantitative [11C]Martinostat-PET Uptake in Primary Breast Cancer, and Correlation with Expression of HDAC Isoforms

Expression levels of HDAC isoforms will be determined from the baseline breast tumor biopsy specimens via western blot analysis. SUV measurements will be collected from the primary breast tumors on PET-MRI.

Correlation of Total Volume of Distribution of Dynamic [11C]Martinostat Uptake with Expression of HDAC Isoforms

Expression levels of HDAC isoforms will be determined from the baseline breast tumor biopsy specimens via western blot analysis. The total volume of [11C]Martinostat distribution will be collected from each PET-MRI.

Comparison of HDAC Isoform Expression by Western Blot Across Breast Tumor Subtypes

Expression levels of HDAC isoforms will be determined from the baseline breast tumor biopsy specimens via western blot analysis and will be analyzed for an association with the tumor subtype as determined by expression of the estrogen receptor, progesterone receptor, and HER2 receptor on clinical pathology.

HDAC Expression Levels in Breast Tumors Compared to HDAC Expression in Adjacent Normal Breast Parenchyma

Comparison of the expression of HDAC in breast tumors to the expression of HDAC in the adjacent normal breast parenchyma. Expression levels of HDAC isoforms will be determined from the baseline breast tumor biopsy specimens via western blot analysis. Expression of HDAC isoforms in the normal breast parenchyma will be determined from biopsy tissue that is collected from the same breast with the cancer, but in a region of healthy breast parenchyma not involved by tumor.

Full Information

NCT ID

NCT03721211

First Posted

October 24, 2018

Last Updated

February 28, 2020

Sponsor

Christine Elizabeth Edmonds

1. Study Identification

Unique Protocol Identification Number

NCT03721211

Brief Title

Imaging With [11C]Martinostat in Breast Cancer

Official Title

Imaging With [11C]Martinostat in Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Principal investigator left the study institution.

Study Start Date

February 1, 2020 (Anticipated)

Primary Completion Date

February 28, 2020 (Actual)

Study Completion Date

October 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Christine Elizabeth Edmonds

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This research study is studying a PET imaging tracer as a possible means of imaging breast cancer. The imaging agent involved in this study is: -[11C]Martinostat (called C-eleven-Martinostat)

Detailed Description

This research study is a Pilot Study, which is the first time investigators are examining this study imaging agent in patients who have breast cancer. The FDA (the U.S. Food and Drug Administration) has approved [11C]Martinostat as an investigational tracer (a type of dye used to for radiographic imaging) in a select few research studies. The FDA has not approved this tracer for any use outside of research. In this research study, the investigators are investigating the use of a PET tracer called [11C]Martinostat in patients with breast cancer. The purpose of the study is to take images that can measure the amount of a protein called histone deacetylase, or 'HDAC' in breast tumors. Proteins are molecules made from amino acids that perform activities in the cell for the body to function in a healthy way. Prior research suggests that HDAC levels or amounts can be altered in some breast tumors. The investigators are trying to develop a method of imaging the HDAC protein in breast tumors. This could help them to study protein changes that occur in some breast tumors, and potentially help guide treatment of breast tumors in the future. In this study, the investigators will take the pictures of the participant's chest, including the breasts, using a PET/MRI scanner. The investigators will the study tracer, or dye, called [11C]Martinostat to make these detailed pictures. [11C]Martinostat was initially developed to image the HDAC protein within the brain, because amounts or levels of HDAC can be altered in some diseases of the brain. In these previous studies of [11C]Martinostat conducted in humans, there were no adverse events (there have been no problems). While this is not the first time [11C]Martinostat has been used in humans, it is the first study in which the investigators are using this tracer to study breast cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast Cancer

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

[11C]Martinostat

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

[11C]Martinostat

Other Intervention Name(s)

Martinostat

Intervention Description

a type of dye used for radiographic imaging of the HDAC protein

Intervention Type

Device

Intervention Name(s)

MR-PET scanner

Intervention Description

PET, or positron emission tomography, is a type of imaging test that uses a tracer, or dye, to make detailed pictures showing the activities of the cells that make up tissues and organs

Primary Outcome Measure Information:

Title

PET-MRI Visualization and Quantification of Breast Tumor Uptake of [11C]Martinostat Above Background Uptake, as Assessed by SUV Measurements

Description

Time Frame

up to 2 years

Secondary Outcome Measure Information:

Title

Quantitative [11C]Martinostat-PET Uptake in Primary Breast Cancer, and Correlation with Expression of HDAC Isoforms

Description

Time Frame

up to 2 years

Title

Correlation of Total Volume of Distribution of Dynamic [11C]Martinostat Uptake with Expression of HDAC Isoforms

Description

Time Frame

up to 2 years

Title

Comparison of HDAC Isoform Expression by Western Blot Across Breast Tumor Subtypes

Description

Time Frame

up to 2 years

Title

HDAC Expression Levels in Breast Tumors Compared to HDAC Expression in Adjacent Normal Breast Parenchyma

Description

Time Frame

up to 2 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Be at least 18 years or age (required for legal consent) Have ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A) Have breast imaging findings from mammogram, ultrasound, or breast MRI that are highly suspicious (i.e. coded as BI RADS 5) for breast cancer. Have primary breast tumor that is at least 2 cm in diameter as measured in any dimension on either mammogram, ultrasound, or breast MRI Have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: General Exclusion Criteria Previously treated breast cancer Concurrent malignancy of any type Recent breast surgery (within the past 12 months) on the ipsilateral breast as the current breast tumor Impaired elimination (as defined as having problems with urination) Metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan Participation in a research study/studies involving radiation exposure within the past 12 months Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, major kidney or liver disease, or psychiatric illness/social situations that would limit compliance with study requirements Pregnancy Currently lactating (either breast feeding or breast pumping) Pregnant women are excluded from this study because of the radioactivity of [11C]Martinostat and the resulting risks of teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to administration of [11C]Martinostat, and because lactation may potentially affect the uptake of [11C]Martinostat on PET, breastfeeding women are excluded from the study. General MR and PET Safety Exclusion Criteria: Electrical implants such as cardiac pacemakers or perfusion pumps Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, steel implants, ferromagnetic objects such as jewelry or metal clips in clothing Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions, and any greater than normal potential for cardiac arrest Inability to lie comfortably on a bed inside a PET camera for 90 minutes as assessed by physical examination and medical history (e.g. back pain, arthritis) Pregnancy: A negative serum pregnancy test is required on the day of the PET procedure for female subjects of child-bearing age. Body weight of > 250 lbs (weight limit of the MRI table as well as risks to larger patients from MRI elements)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christine E Edmond, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Massachusetts General Hospital Cancer Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02214

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Imaging With [11C]Martinostat in Breast Cancer

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