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A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer

Primary Purpose

Breast Cancer, Triple Negative Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
hominex-2
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Breast Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Participants must have histologically confirmed operable triple negative breast cancer

    • ER (estrogen receptors) and PR (progesterone receptors) expression must be < 2%
    • HER2 must negative as shown be either 0 or 1+ by immunohistochemistry (if 2+, in situ hybridization method used to define HER2) OR by a HER2: 17 centromere signal of <2.0 using a standard in situ hybridization method.
  • No prior therapy for current breast cancer
  • Operable breast cancer. Participants who are planned to undergo neo-adjuvant chemotherapy are eligible as long as they consent to an additional breast biopsy following the dietary intervention immediately prior to starting chemotherapy
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤1
  • Ability to understand and the willingness to sign a written informed consent document
  • Serum creatinine <ULN (upper limit of normal)
  • Non-pregnant. Women of childbearing potential must have a negative pregnancy test to participate in this study
  • Women of childbearing potential must agree to use effective contraceptives (as discussed with their physician) while participating in this study

Exclusion Criteria:

  • Patients who are receiving any other investigational agents
  • Patients not able to swallow oral medications or with gastrointestinal conditions that may impact absorption of oral medications
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sites / Locations

  • University of Wisconsin Carbone Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hominex-2

Arm Description

Participants will receive an individualized dietary prescription that incorporates a methionine-free amino acid-modified medical food (Hominex-2, Abbott Nutrition) supplemented with low-methionine foods. Hominex-2 contains a mixture of L-amino acids but lacks methionine. Participants will be asked to have an optional non-contrast MRI to assess body composition prior to and at completion of the methionine-restricted (MR) diet. Not completing a scheduled MRI is not considered a protocol deviation. Participants will be followed for 30 days after surgery or biopsy date. Subjects removed from study for unacceptable adverse events (AEs) will be followed until resolution or stabilization of the AE.

Outcomes

Primary Outcome Measures

Change in cell surface expression of TRAIL receptor-2
To determine if methionine restriction can enhance the cell surface expression of TRAIL receptor-2 in triple negative breast cancers.

Secondary Outcome Measures

Safety and tolerability of methionine measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0
To examine the safety and tolerability of methionine restriction in participants with operable triple-negative breast cancer, measured by the number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Effect of methionine restriction on cancer stem cell markers CD44 and CD24
To examine the effect of methionine restriction on the expression of the cancer stem cell markers CD44 and CD24 by immunohistochemistry. Five to ten slides from each time point will be evaluated from baseline and after completion of the methionine restricted diet.
Change in plasma concentrations
To evaluate plasma concentrations of methionine and methionine metabolites before and after methionine restriction. Blood will be collected after an overnight fast before dietary methionine restriction, weekly during methionine restriction and at the completion of the diet. Plasma concentration will be determined by high-throughput targeted LC-MS (liquid chromatography--mass spectrometry) assay.
Change in subject weight
To evaluate subject weight before and after dietary methionine restriction. Subjects will be weighed before starting the diet and weekly (every 7 days +/- 1).
Change in subject BMI
To evaluate subject BMI before and after dietary methionine restriction. Subjects will be weighed before starting the diet and weekly (every 7 days +/- 1).
Change in subject waist circumference
To evaluate subject BMI, waist circumference and metabolic indices before and after dietary methionine restriction. Waist circumference will be measured before starting the diet and weekly (every 7 days +/- 1) while on the methionine restricted diet.
Change in subject metabolic indices
To evaluate subject metabolic indices before and after dietary methionine restriction.
Change in body composition
To evaluate body composition before and after dietary methionine restriction

Full Information

First Posted
June 9, 2017
Last Updated
August 16, 2021
Sponsor
University of Wisconsin, Madison
Collaborators
Avon Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT03186937
Brief Title
A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer
Official Title
A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
funding and slow enrollment
Study Start Date
August 10, 2017 (Actual)
Primary Completion Date
June 21, 2019 (Actual)
Study Completion Date
June 21, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
Avon Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Given preliminary data demonstrating that methionine deprivation enhances cell surface expression of TRAIL receptor-2, the objective of this clinical trial is to confirm that methionine restriction enhances its expression in triple negative breast cancer and to establish the feasibility and acceptability of this dietary intervention in humans. This study will also examine the effect of methionine restriction on cancer stem cells and metabolic health.
Detailed Description
Under the supervision of a registered dietitian, subjects will receive an individualized dietary prescription that incorporates a methionine-free amino acid-modified medical food (Hominex-2, Abbott Nutrition) supplemented with low-methionine foods. Hominex-2 contains a mixture of L-amino acids but lacks methionine. Subjects will be instructed in the preparation of Hominex-2 beverages (approximately 4-5 per day or per dietician recommendation) to deliver 100% of daily protein requirements (0.8 g/kg/day) and 40-45% of the caloric requirements. The remaining calories will be met with low-methionine foods, including fruits, vegetables, grains (e.g., specified cereal and bread), margarine and cooking oils. Subjects will be provided with a list of foods that are low in methionine. Calories will not be restricted. Subjects will be encouraged to follow their usual level of physical activity and instructed to maintain a daily diet and exercise diary that will be reviewed weekly by the dietitian.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Triple Negative Breast Cancer

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hominex-2
Arm Type
Experimental
Arm Description
Participants will receive an individualized dietary prescription that incorporates a methionine-free amino acid-modified medical food (Hominex-2, Abbott Nutrition) supplemented with low-methionine foods. Hominex-2 contains a mixture of L-amino acids but lacks methionine. Participants will be asked to have an optional non-contrast MRI to assess body composition prior to and at completion of the methionine-restricted (MR) diet. Not completing a scheduled MRI is not considered a protocol deviation. Participants will be followed for 30 days after surgery or biopsy date. Subjects removed from study for unacceptable adverse events (AEs) will be followed until resolution or stabilization of the AE.
Intervention Type
Dietary Supplement
Intervention Name(s)
hominex-2
Other Intervention Name(s)
Nut.Tx, Metabol, Methio-Fr
Intervention Description
Hominex-2 is a methionine-free amino acid modified medical supplement
Primary Outcome Measure Information:
Title
Change in cell surface expression of TRAIL receptor-2
Description
To determine if methionine restriction can enhance the cell surface expression of TRAIL receptor-2 in triple negative breast cancers.
Time Frame
Up to 3 weeks
Secondary Outcome Measure Information:
Title
Safety and tolerability of methionine measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
To examine the safety and tolerability of methionine restriction in participants with operable triple-negative breast cancer, measured by the number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Time Frame
Up to 3 weeks
Title
Effect of methionine restriction on cancer stem cell markers CD44 and CD24
Description
To examine the effect of methionine restriction on the expression of the cancer stem cell markers CD44 and CD24 by immunohistochemistry. Five to ten slides from each time point will be evaluated from baseline and after completion of the methionine restricted diet.
Time Frame
Up to 3 weeks
Title
Change in plasma concentrations
Description
To evaluate plasma concentrations of methionine and methionine metabolites before and after methionine restriction. Blood will be collected after an overnight fast before dietary methionine restriction, weekly during methionine restriction and at the completion of the diet. Plasma concentration will be determined by high-throughput targeted LC-MS (liquid chromatography--mass spectrometry) assay.
Time Frame
Up to 3 weeks
Title
Change in subject weight
Description
To evaluate subject weight before and after dietary methionine restriction. Subjects will be weighed before starting the diet and weekly (every 7 days +/- 1).
Time Frame
Up to 3 weeks
Title
Change in subject BMI
Description
To evaluate subject BMI before and after dietary methionine restriction. Subjects will be weighed before starting the diet and weekly (every 7 days +/- 1).
Time Frame
Up to 3 weeks
Title
Change in subject waist circumference
Description
To evaluate subject BMI, waist circumference and metabolic indices before and after dietary methionine restriction. Waist circumference will be measured before starting the diet and weekly (every 7 days +/- 1) while on the methionine restricted diet.
Time Frame
Up to 3 weeks
Title
Change in subject metabolic indices
Description
To evaluate subject metabolic indices before and after dietary methionine restriction.
Time Frame
Up to 3 weeks
Title
Change in body composition
Description
To evaluate body composition before and after dietary methionine restriction
Time Frame
Up to 3 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have histologically confirmed operable triple negative breast cancer ER (estrogen receptors) and PR (progesterone receptors) expression must be < 2% HER2 must negative as shown be either 0 or 1+ by immunohistochemistry (if 2+, in situ hybridization method used to define HER2) OR by a HER2: 17 centromere signal of <2.0 using a standard in situ hybridization method. No prior therapy for current breast cancer Operable breast cancer. Participants who are planned to undergo neo-adjuvant chemotherapy are eligible as long as they consent to an additional breast biopsy following the dietary intervention immediately prior to starting chemotherapy ECOG (Eastern Cooperative Oncology Group) performance status ≤1 Ability to understand and the willingness to sign a written informed consent document Serum creatinine <ULN (upper limit of normal) Non-pregnant. Women of childbearing potential must have a negative pregnancy test to participate in this study Women of childbearing potential must agree to use effective contraceptives (as discussed with their physician) while participating in this study Exclusion Criteria: Patients who are receiving any other investigational agents Patients not able to swallow oral medications or with gastrointestinal conditions that may impact absorption of oral medications Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kari Wisinski, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.uwhealth.org/uw-carbone-cancer-center/47424
Description
UW Carbone Cancer Center Homepage

Learn more about this trial

A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer

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