Metabolic Pathway Analysis for Pancreatic Cancer

Recruiting at 2 trial locations

Overseen By Howard Hochster, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Chemotherapy, Immunotherapy, Biologic therapy

Disqualifiers: Active malignancy, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how pancreatic cancer cells obtain the nutrients they need to survive. During surgery, doctors will administer a special sugar (U-13C-glucose) to track how cancer cells utilize these nutrients. This research may help scientists understand the differences between cancer cells and normal pancreatic cells. The trial is suitable for individuals with pancreatic adenocarcinoma who are scheduled for therapeutic conventional surgery and consent to additional biopsies for research. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new insights in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are receiving any anti-cancer therapy, you may not be eligible for this trial unless you are part of the group treated with neoadjuvant chemotherapy.

What prior data suggests that this method is safe for tracing metabolic activity in pancreatic cancer?

Research shows that the treatment used in this trial, called uniformly-labeled [13C]glucose, is generally well-tolerated. This special type of glucose helps researchers observe how cancer cells use nutrients. In past studies, it safely tracked how tumors process glucose. The body uses this glucose like regular glucose, but its unique label allows researchers to track its path.

No direct evidence indicates serious side effects from using uniformly-labeled [13C]glucose. Studies mainly focus on its effectiveness in tracking metabolic activity rather than safety issues. Given its use, this compound is considered safe for humans when administered under controlled conditions during medical procedures. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the metabolic pathways of pancreatic cancer using a unique approach. Unlike traditional treatments that primarily focus on surgical removal or chemotherapy, this study uses a special type of glucose, labeled with carbon-13, to trace how cancer cells metabolize energy. This method could uncover crucial insights into the cancer's metabolism, potentially leading to more targeted and effective treatments. By understanding these pathways better, scientists hope to develop interventions that can disrupt the cancer's energy supply, offering new hope for patients battling this tough condition.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that a special type of glucose, called [13C]glucose, can help track how pancreatic cancer cells use nutrients. In this trial, participants will receive uniformly-labeled [13C]glucose to analyze metabolic pathways. This method enables doctors to observe how these cancer cells process glucose differently from normal cells. Studies have found that using [13C]glucose to image glucose use can help identify different types of cancer cells based on their activity. This approach could reveal important details about how pancreatic tumors grow and survive. Understanding these processes may lead to new ways to target and treat pancreatic cancer effectively. ^{1 2 4 6 7}

Who Is on the Research Team?

Howard S. Hochster

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

This trial is for adults with pancreatic adenocarcinoma, eligible for surgery. It includes both untreated patients and those who've had chemotherapy but no other cancer treatments like radiation or immunotherapy. Participants must understand the study's experimental nature and consent to biopsies during surgery.

Inclusion Criteria

I agree to have extra biopsies taken during my surgery for research.

All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry

I have pancreatic cancer and am a candidate for surgery aimed at curing it, with or without prior chemotherapy.

Exclusion Criteria

I am currently undergoing or will undergo chemotherapy, immunotherapy, or biologic therapy.

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)

I have another active cancer besides the one being treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive uniformly-labeled [13C]glucose intravenously over 10 minutes and then over up to 120 minutes until time of biopsy, followed by surgery and biopsy per standard of care

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Biopsy
• Therapeutic Conventional Surgery
• Uniformly-labeled [13C]glucose

Trial Overview The trial studies how pancreatic cancer cells manage nutrients by using a special form of glucose given during surgery. Researchers will compare the metabolism of cancerous and normal cells from biopsies to better understand the disease.

How Is the Trial Designed?

Group I: Basic science (uniformly-labeled [13C]glucose) Experimental Treatment 3 Interventions

Patients receive uniformly-labeled \[13C\]glucose IV over 10 minutes and then over up to 120 minutes until time of biopsy. Patients then undergo surgery and biopsy per standard of care.

Therapeutic Conventional Surgery is already approved in United States, European Union for the following indications:

Approved in United States as Therapeutic Conventional Surgery for:

• Resectable p16+ Locally Advanced Oropharynx Cancer

Approved in European Union as Transoral Surgical Resection for:

• HPV-positive oropharyngeal cancer

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A systematic review of 710 papers identified 107 studies on glycolytic enzymes and 28 on mitochondrial oxidative phosphorylation enzymes in pancreatic ductal adenocarcinoma (PDAC), revealing consistent over-expression of glycolytic enzymes that support rapid energy production, characteristic of the Warburg effect.

Targeting specific glycolytic enzymes with metabolic inhibitors showed promising effects on PDAC, suggesting these enzymes could be potential therapeutic targets, although the role of mitochondrial oxidative phosphorylation enzymes remains less understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose metabolic phenotype of pancreatic cancer. Chan, AK., Bruce, JI., Siriwardena, AK.[2018]

In a study using a genetically engineered mouse model of pancreatic cancer, significant metabolic changes were observed even in the early stages of tumor development, indicating that these alterations may play a role in cancer progression.

The research highlighted that glycolysis and the pentose phosphate pathway are notably upregulated in pancreatic cancer cells, suggesting that targeting these metabolic pathways could be a potential strategy for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Alterations in Pancreatic Cancer Progression. Vernucci, E., Abrego, J., Gunda, V., et al.[2020]

Neoadjuvant chemotherapy (NAC) with albumin-bound paclitaxel and gemcitabine induces significant metabolic reprogramming in pancreatic ductal adenocarcinoma (PDAC), enhancing its immunogenicity and altering metabolic patterns.

High expression of the CD36 protein is associated with poorer survival outcomes in PDAC patients post-chemotherapy, and targeting CD36 has been shown to improve the effectiveness of chemotherapy in both laboratory and patient-derived models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting neoadjuvant chemotherapy-induced metabolic reprogramming in pancreatic cancer promotes anti-tumor immunity and chemo-response. Tang, R., Xu, J., Wang, W., et al.[2023]

Pancreatic ductal adenocarcinoma is becoming a leading cause of cancer-related deaths due to challenges in early detection and effective treatment.

Recent research into the altered metabolic networks of pancreatic cancer cells offers promising new avenues for developing detection methods and treatment strategies for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Employing Metabolism to Improve the Diagnosis and Treatment of Pancreatic Cancer. Halbrook, CJ., Lyssiotis, CA.[2018]

Pancreatic ductal adenocarcinoma is a highly aggressive cancer that is often diagnosed at a late stage, making it difficult to treat and a leading cause of cancer deaths in the U.S.

Recent research highlights the importance of understanding the tumor's metabolism and signaling pathways, such as Ras signaling and lipid metabolism, which could lead to the development of more effective therapies for this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism addiction in pancreatic cancer. Blum, R., Kloog, Y.[2022]

Pancreatic ductal adenocarcinoma (PDAC) is extremely deadly, with a mortality rate over 95%, and is characterized by a harsh acidic microenvironment that promotes cancer cell metabolic reprogramming and resistance to treatments.

Research indicates that targeting the altered metabolic pathways in PDAC, either alone or alongside traditional chemotherapy, may offer new therapeutic strategies to improve treatment outcomes for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic reprogramming by driver mutation-tumor microenvironment interplay in pancreatic cancer: new therapeutic targets. Andersen, HB., Ialchina, R., Pedersen, SF., et al.[2023]

A 16-gene prognostic signature related to metabolic pathways was developed to predict overall survival and recurrence in pancreatic ductal adenocarcinoma (PDAC), showing its importance in the disease's progression.

The gbcx-related risk score (gbcxMRS) not only identified poor PDAC subtypes but also indicated potential drug sensitivity to treatments like irinotecan and docetaxel, suggesting its utility in guiding therapy choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust Validation and Comprehensive Analysis of a Novel Signature Derived from Crucial Metabolic Pathways of Pancreatic Ductal Adenocarcinoma. Gu, W., Mo, S., Wang, Y., et al.[2022]

A study analyzing 163 pancreatic ductal adenocarcinoma (PDAC) tissue samples identified significant alterations in 51 tissue metabolites and 26 serum metabolites, highlighting the γ-glutamyl cycle as a key metabolic pathway affected in PDAC.

5-oxoproline was found to be the most significantly decreased biomarker in PDAC, suggesting it could serve as a potential target for improving diagnosis and treatment strategies for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of the γ-glutamyl cycle as a novel therapeutic target and 5-oxoproline as a new biomarker for diagnosing pancreatic cancer. Wang, W., Tian, X., Yan, L., et al.[2023]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/uniformly-labeled-13cglucose

Clinical Trials Using Uniformly-labeled [13C]glucose - NCI Review the clinical trials studying uniformly-labeled [13c]glucose on this list and use the filters to refine the results by age and location.

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05296421

Investigating Targetable Metabolic Pathways Sustaining ... Patients receive uniformly-labeled [13C]glucose IV over 10 minutes and then over up to 120 minutes until time of biopsy. Patients then undergo surgery and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6706239/

Imaging of glucose metabolism by 13C-MRI distinguishes ... We demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of the metabolism of 13C labeled glucose ...

4. cancer.gov cancer.gov/clinicaltrials/NCI-2022-01787

Investigating Targetable Metabolic Pathways Sustaining ... Giving U-13C-glucose during surgery may allow doctors to trace the metabolic activity of pancreatic cancer in research experiments done in the laboratory. These ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9367608/

Metabolic Pathways as a Novel Landscape in Pancreatic ... In this review, we describe the main metabolic mechanisms involved in PDAC growth and the biological features that may favor its onset and progression.

6. elifesciences.org elifesciences.org/articles/46312

Imaging of glucose metabolism by 13C-MRI distinguishes ... Using noise suppression, real-time imaging of glucose metabolism is possible by 13C MRI and reveals previously undetected metabolic ...

7. qeios.com qeios.com/read/E90PDS/pdf

Uniformly-labeled [U-13C]glucose Upon administration of uniformly- labeled [U-13C] glucose, the glucose is taken up and metabolized by tumors and the 13C- containing metabolites can be imaged ...