Metabolic Pathway Tracer for Breast Cancer

Recruiting at 1 trial location

Overseen By Coral Omene, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Rutgers, The State University of New Jersey

Disqualifiers: Triple negative, Her2+, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 2-3 hours

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how breast cancer cells process energy, focusing on the HR+/Her2- subtype, which is common but not fully studied. Researchers will use U-13C-glucose, a labeled form of glucose, to track the cells' metabolic activity during surgery. This approach will help reveal how cancer cells fuel themselves and may guide future treatments. The trial seeks participants with early-stage HR+/Her2- breast cancer who have not yet received certain therapies and are preparing for surgery. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could shape future cancer treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that U-13C-glucose is safe for use in metabolic studies?

Research has shown that U-13C-glucose is safe for humans. Scientists have used it in other studies to understand how cells use energy and nutrients. This compound allows researchers to observe cellular processes without causing harm.

Participants in similar studies with related compounds have tolerated them well, experiencing no serious side effects. Since U-13C-glucose tracks how the body processes substances rather than treating cancer directly, it is generally considered low-risk.

The specific study on U-13C-glucose for breast cancer reported no harmful effects, supporting its safety in this context. This should reassure potential participants about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Metabolic Pathway Tracer for Breast Cancer trial because it uses U-13C-glucose to delve into the metabolic processes of hormone receptor-positive, HER2-negative breast cancer, a subtype that makes up most breast cancer cases. Unlike traditional treatments that focus on targeting cancer cells or blocking hormone receptors, this approach uniquely traces how cancer cells metabolize glucose. This innovative angle could reveal new insights into cancer metabolism, which might lead to novel treatment strategies and improve our understanding of how this common subtype of breast cancer behaves at a metabolic level.

What evidence suggests that U-13C-glucose is effective for analyzing metabolic activity in HR+/Her2- breast cancer?

In this trial, U-13C-glucose will track how breast cancer cells obtain energy. Research has shown that U-13C-glucose helps scientists identify the processes cancer cells use to grow and survive. Understanding these processes allows researchers to find potential weaknesses in the cancer cells. While this method does not directly treat breast cancer, it provides crucial information about the cancer's behavior. This insight may lead to better treatments in the future. ^{3 6 7 8 9}

Who Is on the Research Team?

Coral Omene, MD, PhD

Principal Investigator

Cancer Institute of New Jersey Rutgers

Are You a Good Fit for This Trial?

This trial is for individuals with HR+/HER2- breast cancer, who haven't had neoadjuvant therapy and are set for curative surgery. They must be willing to provide tissue samples during surgery and not be part of another clinical study or have other active cancers.

Inclusion Criteria

I am a candidate for surgery to remove my cancer and have not had any pre-surgery treatments.

My breast cancer is hormone receptor positive and HER2 negative.

I agree to have small samples of my tumor and normal tissue taken during surgery for research.

Exclusion Criteria

I have another active cancer besides the one being treated.

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.

Is of child-bearing potential who has not had a recent negative pregnancy test done outside of this clinical trial (i.e., as part of standard preparation for diagnosis and treatment for her cancer)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a glucose infusion during routine breast cancer surgery, with tumor biopsy and blood sample collection for metabolic analysis

2-3 hours

1 visit (in-person, intraoperative)

Follow-up

Participants are monitored for metabolic activity analysis using collected samples

3-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• U-13C-glucose

Trial Overview The trial studies how hormone receptor-positive, HER2-negative breast cancer cells process sugar by using a special form of glucose called U-13C-glucose during surgical resection of the tumor.

How Is the Trial Designed?

Group I: Metabolic activity of Hormone Receptor Positive (HR+)/Her 2 Negative (Her2-) Breast cancer Experimental Treatment 1 Intervention

Administration of U-13C-glucose to participants with early-stage HR+/Her2- breast cancer fitting criteria, will be done intraoperatively at the time of resection, as well as blood sample collection. This will allow for in depth evaluation of glycolysis as well as TCA cycle, lipid and amino acid metabolism and comprehensive genomic analyses to complement the metabolic assays that will be done by the Ludwig Institute of Cancer Research. HR+/Her2- breast cancer subtype is chosen for this feasibility pilot study given that metabolic studies have not been done in this subtype of breast cancer and it makes up the majority of breast cancer cases.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Ludwig Institute for Cancer Research

Collaborator

Trials

62

Recruited

1,700+

Published Research Related to This Trial

This study presents a detailed protocol for using 13C-stable isotope tracing to analyze the metabolic processes in HER2+ breast cancer brain metastases in mice, which is crucial for understanding tumor cell dependencies.

The method includes steps for injecting cancer cells to create brain metastases, infusing stable isotopes, and analyzing metabolites, providing a comprehensive approach for future cancer research and potential treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimized protocol for stable isotope tracing and steady-state metabolomics in mouse HER2+ breast cancer brain metastasis. Parida, PK., Marquez-Palencia, M., Kaushik, AK., et al.[2022]

6-[(18)F]FDF, a new PET radiotracer, shows promise for imaging GLUT5 expression in breast cancer, demonstrating significant uptake in breast cancer cells independent of glucose levels, which could improve detection compared to traditional [(18)F]FDG.

In vivo studies revealed that 6-[(18)F]FDF accumulates effectively in EMT-6 tumors, suggesting its potential as a more specific imaging agent for certain breast cancers, particularly those expressing GLUT5 and ketohexokinase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiopharmacological evaluation of 6-deoxy-6-[18F]fluoro-D-fructose as a radiotracer for PET imaging of GLUT5 in breast cancer. Wuest, M., Trayner, BJ., Grant, TN., et al.[2016]

In a study of 146 patients with invasive ductal carcinoma of the breast, a significant positive correlation was found between 18F-FDG uptake and mitochondrial activity, indicating that higher metabolic activity in cancer cells is linked to worse outcomes.

Increased 18F-FDG uptake was associated with a shorter disease-free survival (DFS), suggesting that measuring this uptake can help predict patient prognosis, with a specific cut-off value of 7.76 for pSUVmax identified as significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reverse Warburg Effect-Related Mitochondrial Activity and 18F-FDG Uptake in Invasive Ductal Carcinoma. Choi, BW., Jeong, YJ., Park, SH., et al.[2022]

Using (13)C metabolic flux analysis, researchers identified that [1,2-(13)C(2)]glucose is the most effective tracer for accurately estimating metabolic fluxes in cancer cell metabolism, particularly for glycolysis and the pentose phosphate pathway.

The study also found that [U-(13)C(5)]glutamine is the best tracer for analyzing the tricarboxylic acid (TCA) cycle, providing essential insights for designing more effective metabolic flux analysis experiments in mammalian cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells. Metallo, CM., Walther, JL., Stephanopoulos, G.[2021]

The study demonstrated that the monoclonal antibody 213Bi-anti-EGFR-MAb effectively decreased glucose metabolism in bladder cancer cells (EJ28Luc) by reducing the incorporation of carbon from glucose into key amino acids, indicating a strong early treatment response.

In contrast, glioma cells (LN18) did not show the same metabolic response despite being killed by the treatment, suggesting that the effectiveness of the radionuclide therapy may vary between different types of cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate. Feuerecker, B., Biechl, P., Seidl, C., et al.[2021]

In a study of 70 patients with primary breast carcinoma, the differential absorption ratio (DAR) calculated from FDG PET scans was found to be a significant prognostic indicator, with higher DAR values correlating to worse overall and relapse-free survival rates.

Patients with a high DAR (≥3.0) had significantly poorer prognoses compared to those with a low DAR (<3.0), highlighting the potential of FDG PET as a tool for predicting outcomes in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose. Oshida, M., Uno, K., Suzuki, M., et al.[2022]

A new method for delivering 13C6-glucose through a stress-free liquid diet in rodents allows for significant enrichment of metabolic products, enabling detailed study of various metabolic pathways in mouse tissues over 12 to 48 hours.

This approach revealed that patient-derived lung tumor xenografts utilize glucose from the liver for synthesizing important compounds like glutamate and glutathione, highlighting differences in glucose metabolism between primary tumors and their metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive liquid diet delivery of stable isotopes into mouse models for deep metabolic network tracing. Sun, RC., Fan, TW., Deng, P., et al.[2019]

The study used Stable Isotope Resolved Metabolomics to analyze metabolic pathways in different breast cell types, revealing that glycolysis does not correlate with breast cancer cell proliferation, while glutaminolysis is crucial for pyrimidine synthesis across all cell types.

Metabolic differences were observed between in vitro cultures and tumor xenografts of breast cancer cell lines, indicating that the tumor microenvironment significantly influences glucose metabolism, although the inherent metabolic distinctions between the cell lines remained consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics. Lane, AN., Tan, J., Wang, Y., et al.[2020]

The newly synthesized compound 6-deoxy-6-fluoro-D-fructose (6FDF) shows promise for improved imaging of breast cancer by targeting overexpressed fructose transporters in cancer cells.

In studies with breast cancer cell lines, 6FDF demonstrated effective transport and accumulation, indicating its potential for use in PET imaging, with further testing planned in mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and characterization of 6-deoxy-6-fluoro-D-fructose as a potential compound for imaging breast cancer with PET. Trayner, BJ., Grant, TN., West, FG., et al.[2009]

The study utilized 2-deoxy-D-[6-13C]glucose to track both the transport and phosphorylation processes in MCF-7 breast cancer cells, providing insights into glucose metabolism in cancer cells.

This method was applied in both in vitro (lab) settings and in vivo (live mice) with subcutaneous tumors, demonstrating its potential for studying cancer metabolism in real biological systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the transport and phosphorylation of 2-deoxy-D-glucose in tumor cells in vivo and in vitro by 13C nuclear magnetic resonance spectroscopy. Navon, G., Lyon, RC., Kaplan, O., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05736367

Investigating the Metabolic Pathways in Hormone Receptor ... Participants will be asked to receive a glucose infusion (U-13C- glucose intravenous) during routine breast cancer surgery at which time, tumor biopsy ...

2. withpower.com withpower.com/trial/phase-1-breast-neoplasms-5-2023-36541

Metabolic Pathway Tracer for Breast Cancer U-13C-glucose is unique because it acts as a tracer to study the metabolic pathways in breast cancer cells, helping researchers understand how these cells ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27812873/

Glucose Tracer to Study Metabolic Changes in Oncogene ... Metabolic flux analysis (MFA) is a comprehensive technique that allows researchers to create a map of cellular metabolic state. This method is extensively ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10341343/

Role of Glucose Metabolic Reprogramming in Breast ... Here, we review the roles and mechanisms of action of glucose metabolic reprogramming in breast cancer progression and drug resistance.

5. cell.com cell.com/cms/10.1016/j.cmet.2021.12.001/attachment/49337ff4-30b4-4c60-92fa-d53ea2aa0899/mmc2.pdf

Metabolic diversity within breast cancer brain-tropic cells ... In brief. The basis for disparate metastatic fitness among disseminated tumor cells of similar oncotype within a distal organ is.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11297952/

Targeting fatty acid oxidation enhances response to HER2- ... The authors show that inhibiting fatty acid oxidation in HER2-driven breast cancers delays tumor growth and enhances the effectiveness of HER2-targeted ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1550413121006203

Metabolic diversity within breast cancer brain-tropic cells ... Patients with HER2+ breast cancer and synchronous brain metastases, although relatively rare, have a median overall survival of around 6 months ...

8. mdpi.com mdpi.com/2218-1989/6/4/30

Optimized Method for Untargeted Metabolomics Analysis of ... Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are ...

9. isotope.com isotope.com/minimal-media-reagents/d-glucose-u-13c6-clm-1396-1

D-Glucose (U-¹³C₆, 99%) Isotopically labeled glucose has been used in metabolic tracer studies, for fatty acid synthesis, as a minimal media reagent, and as an internal standard.