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

NCT ID: NCT03186937

Last Updated: 2021-08-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-10
• Study Completion Date: 2019-06-21

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.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

hominex-2

Intervention Type: DIETARY_SUPPLEMENT

Hominex-2 is a methionine-free amino acid modified medical supplement

Interventions

hominex-2

Hominex-2 is a methionine-free amino acid modified medical supplement

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Nut.Tx; Metabol; Methio-Fr

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Avon Foundation

OTHER

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kari Wisinski, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Countries

United States

Related Links

http://www.uwhealth.org/uw-carbone-cancer-center/47424

UW Carbone Cancer Center Homepage

Other Identifiers

2016-1532

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2017-01047

Identifier Type: REGISTRY

Identifier Source: secondary_id

A534260

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH\MEDICINE\HEM-ONC

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 11/23/2020

Identifier Type: OTHER

Identifier Source: secondary_id

UW16083

Identifier Type: -

Identifier Source: org_study_id