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

University of Wisconsin (UW)

Status and phase: Terminated; Phase 2

Conditions: Breast Cancer; Triple Negative Breast Cancer

Treatments: Dietary Supplement: hominex-2

Study type: Interventional

Funder types: Other

Identifiers

NCT03186937

Protocol Version 11/23/2020 (Other Identifier)

NCI-2017-01047 (Registry Identifier)

2016-1532 (Other Identifier)

UW16083

A534260 (Other Identifier)

SMPH\MEDICINE\HEM-ONC (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: Female

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Hominex-2

Experimental group

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.

Treatment:

Dietary Supplement: hominex-2