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

NCT03186937 | Terminated Phase 2

• 6 other identifiers: UW160832016-1532NCI-2017-01047A534260SMPH\MEDICINE\HEM-ONCProtocol Version 11/23/2020
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 3 weeks

Secondary Outcomes (8)

• Safety and tolerability of methionine measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Up to 3 weeks

• Effect of methionine restriction on cancer stem cell markers CD44 and CD24

  Up to 3 weeks

• Change in plasma concentrations

  Up to 3 weeks

• Change in subject weight

  Up to 3 weeks

• Change in subject BMI

  Up to 3 weeks

Study Arms (1)

Hominex-2

EXPERIMENTAL

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

Interventions

hominex-2 DIETARY_SUPPLEMENT

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

Also known as: Nut.Tx, Metabol, Methio-Fr

Hominex-2

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Avon Foundation: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• UW Carbone Cancer Center Homepage

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Kari Wisinski, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: June 14, 2017
• Study Start: August 10, 2017
• Primary Completion: June 21, 2019
• Study Completion: June 21, 2019
• Last Updated: August 18, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)