Triple Negative Breast CancerNCT03457779
Pilot Study To Investigate Targetable Metabolic Pathways Sustaining Triple Negative Breast Cancer
A study testing Glucose in people with Triple Negative Breast Cancer, run by Baylor Research Institute at 1 site in United States.
Trial summary
The primary objective is to describe and discover new insights into the glucose, amino acid, and lipid metabolic dependencies of TNBC via nuclear magnetic resonance (NMR) spectroscopy analysis of in vivo [1,2-13C] glucose-labeled breast cancer biopsies. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- Glucose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2018to 31 Dec 2020
- Phase
- Interventional
- 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
- A patient will be considered for enrollment in this study if all the following criteria are met:
- Female patients ≥18 years of age.
- Have TNBC defined as invasive ductal cancer: ER- tumors with <10% of tumor nuclei immunoreactive; PR- tumors with <10% of tumor nuclei immunoreactive; HER2-negative defined as follows:
- FISH-negative (FISH ratio <2.0), or
- IHC 0-1+, or
- IHC 2+ AND FISH-negative (FISH ratio<2.0)
Show all 18Show fewer
- Adequate hematologic function, defined by:
- Absolute neutrophil count (ANC) >1000/mm3
- Platelet count ≥100,000/mm3
- Hemoglobin >9 g/dL (in the absence of red blood cell transfusion)
- Adequate liver function, defined by:
- AST and ALT ≤ 5 x the upper limit of normal (ULN)
- Total bilirubin ≤1.5 x ULN
- Adequate renal function, defined by:
- Serum creatinine ≤ 2 x ULN or calculated creatinine clearance of ≥60 ml/min
- Have blood glucose <250 mg/dL
- Willing to undergo 1 mandatory core biopsy (6 passes) for research purposes.
- All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry.
Who cannot join
- A patient will be ineligible for inclusion in this study any of the following criteria are met:
- Patients receiving any anti-cancer therapy (chemotherapy, immunotherapy, and/or biologic therapy).
- Is currently enrolled, or will enroll in, a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study.
- Has a history of insulin-dependent diabetes.
- Concomitant active malignancy
- Is pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Baylor University Medical Center
Dallas, Texas, 75246
About this study
Official title: Pilot Study To Investigate Targetable Metabolic Pathways Sustaining Triple Negative (TN) Breast Cancer and Associated Genomic Alterations
The primary objective is to describe and discover new insights into the glucose, amino acid, and lipid metabolic dependencies of TNBC via nuclear magnetic resonance (NMR) spectroscopy analysis of in vivo [1,2-13C] glucose-labeled breast cancer biopsies.
The secondary objectives are to correlate the dominant metabolic dependencies of TNBCs with pathologic response to preoperative chemotherapy, and with the cancers' molecular signaling pathways assessed via NGS and RPPA.
Read the detailed description
One of the recognized hallmarks of cancer cells is deregulated cellular metabolism, characterized by enhanced metabolic autonomy compare with non-transformed cells. Tumor cells typically display an overall increase in glucose metabolism, associated with enhanced aerobic glycolysis and decreased oxidative phosphorylation, accompanied by a requirement for a high rate of protein, nucleotide, and fatty acid synthesis to provide the raw materials for cell division. 13C-glucose is a non-radioactive stable isotope tracer that has been widely used in vitro, in vivo, and in patients in a variety of disease settings to study glucose, amino acid, and lipid metabolism, at steady state and following intervention. [1,2-13C] glucose can provide additional information on the activity of the oxidative pentose phosphate pathway versus glycolysis. Administration of intravenous 13C-glucose is a convenient and affordable approach to analyzing the metabolomics of human cancers in their native microenvironments.
The metabolic dependencies of the various breast cancer subtypes are poorly understood. Importantly, in depth analyses of the in situ metabolic processes utilized by triple-negative breast cancers (TNBCs) using state-of-the-art in vivo [1,2-13C]-glucose infusions in patients with TNBC has never been done. In TNBC, oncogenic activation of key signaling pathways leads to altered metabolic programming resulting in an increased dependence on exogenous nutrients such as glucose and glutamine. These data further suggest a hypothesis that TNBCs may employ a cellular mechanism called macropinocytosis to ingest and degrade interstitial albumin to accumulate glutamine. This process may then be exploited for therapeutic gain through enhanced uptake by cells that utilize macropinocytosis to meet their metabolic requirements.
In this study, administration of [1,2-13C]-glucose to patients with TNBC will be done prior to patients undergoing a biopsy of their breast cancer as well as blood sample collection which will allow for in depth evaluation of glycolysis as well as lipid and amino acid metabolism by Joshua Rabinowitz, PhD, at Princeton University who is an international expert in cancer metabolomics. RAS and PI3K pathway and other genomic alterations as well as pathway activation status will be determined by next generation sequencing (NGS) and by reverse phase protein array (RPPA), and will be correlated with the metabolic findings, and both will be assessed in the context of the patients' response to standard preoperative chemotherapy.
- Conditions
- Triple Negative Breast Cancer
- Being tested
- Glucose
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucoseDietary supplement
The first 4 patients enrolled on trial will undergo the research core biopsies of their TNBC without the 13C glucose infusion; these samples will serve as control tissue that will be processed identically to the tissues obtained from patients who received the glucose isotope.
The following 12 patients will receive 6 grams (g) of [1,2-13C] glucose as an IV
| Study group | Role | What they receive |
|---|---|---|
| Non Glucose Arm | Experimental | 4 patients without glucose infusion Receives: Dietary Supplement: Glucose |
| Glucose Arm | Experimental | 12 Patients with glucose infusion Receives: Dietary Supplement: Glucose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amount of glucose, amino acid, and lipid metabolites in TNBC.
Amount of glucose, amino acid, lipid will be measured in 16 patients with TNBC using NMR spectroscopy to see how metabolism is affected in TNBC.
Measured: 2 years
Secondary outcomes (1)
Correlation of signaling pathways in TNBC with response and metabolites.
A panel of key cancer cell signaling pathways will be analyzed in TNBC tissues from 16 patients using phosphoproteomic technology and next generation sequencing. The activated and deactivated pathways will be correlated with standard of care pathologic response (residual disease or no residual disease) and amount of glucose, amino acid, and lipid metabolized.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2018
- Study start8 Feb 2018
- Primary completion8 Apr 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Patients with TNBC will receive \[1,2-13C\]-glucose IV to prior to undergoing a biopsy of their breast cancer and blood collection to allow for in depth evaluation.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joyce O'Shaughnessy, MD, Principal investigator, Texas Oncology/Baylor Scott & White Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03457779
- Sponsor's protocol ID
- 017-396
- Status last verified
- Oct 2021
- First submitted
- 8 Feb 2018
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: For serum collection and storage at the Baylor BPM core, until they are shipped to Princeton University. The key metabolic dependency findings will be correlated with genomic and proteomic alterations assessed by NGS and RPPA, and with patients' response to preoperative chemotherapy.
Publications
Ghergurovich JM, Lang JD, Levin MK, Briones N, Facista SJ, Mueller C, Cowan AJ, McBride MJ, Rodriguez ESR, Killian A, Dao T, Lamont J, Barron A, Su X, Hendricks WPD, Espina V, Von Hoff DD, O'Shaughnessy J, Rabinowitz JD. Local production of lactate, ribose phosphate, and amino acids within human triple-negative breast cancer. Med. 2021 Jun 11;2(6):736-754. doi: 10.1016/j.medj.2021.03.009. Epub 2021 Apr 14.
PubMed 34223403
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study To Investigate Targetable Metabolic Pathways Sustaining Triple Negative (TN) Breast Cancer and Associated Genomic Alterations
- ClinicalTrials.gov ID
- NCT03457779
- Acronym / sponsor ID
- 017-396
- Conditions
- Triple Negative Breast Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Baylor Research InstituteUniversity, hospital or other
- Study start
- 8 Feb 2018 (actual)
- Primary completion
- 8 Apr 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 8 Mar 2018 (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.
The primary objective is to describe and discover new insights into the glucose, amino acid, and lipid metabolic dependencies of TNBC via nuclear magnetic resonance (NMR) spectroscopy analysis of in vivo [1,2-13C] glucose-labeled breast cancer biopsies.
The secondary objectives are to correlate the dominant metabolic dependencies of TNBCs with pathologic response to preoperative chemotherapy, and with the cancers' molecular signaling pathways assessed via NGS and RPPA.
Detailed description
One of the recognized hallmarks of cancer cells is deregulated cellular metabolism, characterized by enhanced metabolic autonomy compare with non-transformed cells. Tumor cells typically display an overall increase in glucose metabolism, associated with enhanced aerobic glycolysis and decreased oxidative phosphorylation, accompanied by a requirement for a high rate of protein, nucleotide, and fatty acid synthesis to provide the raw materials for cell division. 13C-glucose is a non-radioactive stable isotope tracer that has been widely used in vitro, in vivo, and in patients in a variety of disease settings to study glucose, amino acid, and lipid metabolism, at steady state and following intervention. [1,2-13C] glucose can provide additional information on the activity of the oxidative pentose phosphate pathway versus glycolysis. Administration of intravenous 13C-glucose is a convenient and affordable approach to analyzing the metabolomics of human cancers in their native microenvironments.
The metabolic dependencies of the various breast cancer subtypes are poorly understood. Importantly, in depth analyses of the in situ metabolic processes utilized by triple-negative breast cancers (TNBCs) using state-of-the-art in vivo [1,2-13C]-glucose infusions in patients with TNBC has never been done. In TNBC, oncogenic activation of key signaling pathways leads to altered metabolic programming resulting in an increased dependence on exogenous nutrients such as glucose and glutamine. These data further suggest a hypothesis that TNBCs may employ a cellular mechanism called macropinocytosis to ingest and degrade interstitial albumin to accumulate glutamine. This process may then be exploited for therapeutic gain through enhanced uptake by cells that utilize macropinocytosis to meet their metabolic requirements.
In this study, administration of [1,2-13C]-glucose to patients with TNBC will be done prior to patients undergoing a biopsy of their breast cancer as well as blood sample collection which will allow for in depth evaluation of glycolysis as well as lipid and amino acid metabolism by Joshua Rabinowitz, PhD, at Princeton University who is an international expert in cancer metabolomics. RAS and PI3K pathway and other genomic alterations as well as pathway activation status will be determined by next generation sequencing (NGS) and by reverse phase protein array (RPPA), and will be correlated with the metabolic findings, and both will be assessed in the context of the patients' response to standard preoperative chemotherapy.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients with TNBC will receive [1,2-13C]-glucose IV to prior to undergoing a biopsy of their breast cancer and blood collection to allow for in depth evaluation.
| Arm | Type | Receives |
|---|---|---|
| Non Glucose Arm | Experimental | Dietary Supplement: Glucose4 patients without glucose infusion |
| Glucose Arm | Experimental | Dietary Supplement: Glucose12 Patients with glucose infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- A patient will be considered for enrollment in this study if all the following criteria are met:
- Female patients ≥18 years of age.
- Have TNBC defined as invasive ductal cancer: ER- tumors with <10% of tumor nuclei immunoreactive; PR- tumors with <10% of tumor nuclei immunoreactive; HER2-negative defined as follows:
- Adequate hematologic function, defined by:
- Adequate liver function, defined by:
Key exclusion criteria (6 listed)
- A patient will be ineligible for inclusion in this study any of the following criteria are met:
- Patients receiving any anti-cancer therapy (chemotherapy, immunotherapy, and/or biologic therapy).
- Is currently enrolled, or will enroll in, a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study.
- Has a history of insulin-dependent diabetes.
- Concomitant active malignancy
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 |
|---|---|---|
| GlucoseThe first 4 patients enrolled on trial will undergo the research core biopsies of their TNBC without the 13C glucose infusion; these samples will serve as control tissue that will be processed identically to the tissues obtained from patients who received the glucose isotope. The following 12 patients will receive 6 grams (g) of [1,2-13C] glucose as an IV | Dietary supplement | Glucose Arm, Non Glucose Arm |
Primary outcome
Amount of glucose, amino acid, and lipid metabolites in TNBC.
Time frame: 2 years
Amount of glucose, amino acid, lipid will be measured in 16 patients with TNBC using NMR spectroscopy to see how metabolism is affected in TNBC.
1 secondary outcome
Correlation of signaling pathways in TNBC with response and metabolites.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Derived from this study: PubMed 34223403Ghergurovich JM, Lang JD, Levin MK, Briones N, Facista SJ, Mueller C, Cowan AJ, McBride MJ, Rodriguez ESR, Killian A, Dao T, Lamont J, Barron A, Su X, Hendricks WPD, Espina V, Von Hoff DD, O'Shaughnessy J, Rabinowitz JD. Local production of lactate, ribose phosphate, and amino acids within human triple-negative breast cancer. Med. 2021 Jun 11;2(6):736-754. doi: 10.1016/j.medj.2021.03.009. Epub 2021 Apr 14.
- Individual participant dataSharing planned: Yes. For serum collection and storage at the Baylor BPM core, until they are shipped to Princeton University. The key metabolic dependency findings will be correlated with genomic and proteomic alterations assessed by NGS and RPPA, and with patients' response to preoperative chemotherapy.
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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.
Joyce O'Shaughnessy, MD principal investigator
Texas Oncology/Baylor Scott & White Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glucose in people with Triple Negative Breast Cancer, run by Baylor Research Institute 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 18 inclusion and 6 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: finished, as of the sponsor's last update on 8 Oct 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Amount of glucose, amino acid, and lipid metabolites in TNBC. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03457779, which also lists 1 linked publication.
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 8 Oct 2021.