Clinical trial NCT03186937: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Triple Negative Breast Cancer
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Avon Foundation
First posted: 2017-06-14
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Change in cell surface expression of TRAIL receptor-2
timeFrame: Up to 3 weeks
Secondary outcomes:
measure: Safety and tolerability of methionine measured by number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to 3 weeks
measure: Effect of methionine restriction on cancer stem cell markers CD44 and CD24
timeFrame: Up to 3 weeks
measure: Change in plasma concentrations
timeFrame: Up to 3 weeks
measure: Change in subject weight
timeFrame: Up to 3 weeks
measure: Change in subject BMI
timeFrame: Up to 3 weeks
measure: Change in subject waist circumference
timeFrame: Up to 3 weeks
measure: Change in subject metabolic indices
timeFrame: Up to 3 weeks
measure: Change in body composition
timeFrame: Up to 3 weeks
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Kari Wisinski, MD
role: PRINCIPAL_INVESTIGATOR
References: