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

This study is currently recruiting participants.
Verified September 2017 by University of Wisconsin, Madison
Sponsor:
ClinicalTrials.gov Identifier:
NCT03186937
First Posted: June 14, 2017
Last Update Posted: September 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
Avon Foundation
Information provided by (Responsible Party):
University of Wisconsin, Madison
  Purpose
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.

Condition Intervention Phase
Breast Cancer Triple Negative Breast Cancer Dietary Supplement: hominex-2 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Change in cell surface expression of TRAIL receptor-2 [ Time Frame: Up to 3 weeks ]
    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 [ Time Frame: Up to 3 weeks ]
    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 [ Time Frame: Up to 3 weeks ]
    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 [ Time Frame: Up to 3 weeks ]
    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 [ Time Frame: Up to 3 weeks ]
    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 [ Time Frame: Up to 3 weeks ]
    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 [ Time Frame: Up to 3 weeks ]
    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 [ Time Frame: Up to 3 weeks ]
    To evaluate subject metabolic indices before and after dietary methionine restriction.

  • Change in body composition [ Time Frame: Up to 3 weeks ]
    To evaluate body composition before and after dietary methionine restriction


Estimated Enrollment: 25
Actual Study Start Date: August 10, 2017
Estimated Study Completion Date: June 30, 2019
Estimated Primary Completion Date: June 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hominex-2

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.

Dietary Supplement: hominex-2
Hominex-2 is a methionine-free amino acid modified medical supplement
Other Names:
  • Nut.Tx
  • Metabol
  • Methio-Fr

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 (4-5 per day) 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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186937


Contacts
Contact: Cancer Connect 800-622-8922 cancerconnect@uwcarbone.wisc.edu

Locations
United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Cancer Connect    800-622-8922    cancerconnect@uwcarbone.wisc.edu   
Principal Investigator: Ruth O'Regan, MD         
Sponsors and Collaborators
University of Wisconsin, Madison
National Cancer Institute (NCI)
Avon Foundation
Investigators
Principal Investigator: Ruth O'Regan, MD University of Wisconsin, Madison
  More Information

Additional Information:
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03186937     History of Changes
Other Study ID Numbers: UW16083
2016-1532 ( Other Identifier: Institutional Review Board )
P30CA014520 ( U.S. NIH Grant/Contract )
NCI-2017-01047 ( Registry Identifier: NCI CTRP )
First Submitted: June 9, 2017
First Posted: June 14, 2017
Last Update Posted: September 6, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases