Breast CancerPhase 2NCT03186937
A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer
A Phase 2 study testing hominex-2 in people with Breast Cancer and Triple Negative Breast Cancer, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Triple Negative Breast Cancer
- What is being tested?
- hominex-2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2017to 21 Jun 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
About this study
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.
Read the 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
- Being tested
- hominex-2
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hominex-2Dietary supplement
Also called Nut.Tx, Metabol, Methio-Fr
Hominex-2 is a methionine-free amino acid modified medical supplement
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: hominex-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Up to 3 weeks
Effect of methionine restriction on cancer stem cell markers CD44 and CD24
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.
Measured: Up to 3 weeks
Change in plasma concentrations
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.
Measured: Up to 3 weeks
Change in subject weight
To evaluate subject weight before and after dietary methionine restriction. Subjects will be weighed before starting the diet and weekly (every 7 days +/- 1).
Measured: Up to 3 weeks
Change in subject BMI
To evaluate subject BMI before and after dietary methionine restriction. Subjects will be weighed before starting the diet and weekly (every 7 days +/- 1).
Measured: Up to 3 weeks
Change in subject waist circumference
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.
Measured: Up to 3 weeks
Change in subject metabolic indices
To evaluate subject metabolic indices before and after dietary methionine restriction.
Measured: Up to 3 weeks
Change in body composition
To evaluate body composition before and after dietary methionine restriction
Measured: Up to 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start10 Aug 2017
- Primary completion21 Jun 2019
- Study completion21 Jun 2019
Why it stopped: funding and slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Avon Foundation
- Responsible party
- Sponsor
- Investigators
- Kari Wisinski, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03186937
- Sponsor's protocol ID
- UW16083
- Other IDs
- 2016-1532, NCI-2017-01047, A534260, SMPH\MEDICINE\HEM-ONC, Protocol Version 11/23/2020
- Status last verified
- Aug 2021
- First submitted
- 9 Jun 2017
- Last updated
- 18 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT03186937
- Acronym / sponsor ID
- UW16083
- Conditions
- Breast Cancer, Triple Negative Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: funding and slow enrollment
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Avon Foundation
- Study start
- 10 Aug 2017 (actual)
- Primary completion
- 21 Jun 2019 (actual)
- Study completion
- 21 Jun 2019 (actual)
- First posted
- 14 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hominex-2 | Experimental | Dietary Supplement: hominex-2Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Participants must have histologically confirmed operable triple negative breast cancer
- 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
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hominex-2Also: Nut.Tx, Metabol, Methio-FrHominex-2 is a methionine-free amino acid modified medical supplement | Dietary supplement | Hominex-2 |
Primary outcome
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.
8 secondary outcomes
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
Effect of methionine restriction on cancer stem cell markers CD44 and CD24
Time frame: Up to 3 weeks
Change in plasma concentrations
Time frame: Up to 3 weeks
Change in subject weight
Time frame: Up to 3 weeks
Change in subject BMI
Time frame: Up to 3 weeks
Change in subject waist circumference
Time frame: Up to 3 weeks
Change in subject metabolic indices
Time frame: Up to 3 weeks
Change in body composition
Time frame: Up to 3 weeks
Results and safety
The study was stopped early (reason given: funding and slow enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2021.
- UW Carbone Cancer Center HomepageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kari Wisinski, MD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing hominex-2 in people with Breast Cancer and Triple Negative Breast Cancer, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: funding and slow enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cell surface expression of TRAIL receptor-2 (time frame: Up to 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2021.