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

Trial Summary

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 data supports the effectiveness of this treatment for pancreatic cancer?

Research indicates that pancreatic cancer cells have altered metabolic pathways, which can be targeted for treatment. The use of uniformly-labeled [13C]glucose helps in understanding these metabolic changes, potentially leading to more effective therapies by targeting the cancer's unique metabolism. ^{1 2 3 4 5}

Is the treatment for metabolic pathway analysis in pancreatic cancer safe for humans?

The research articles provided do not contain specific safety data for the treatment involving metabolic pathway analysis in pancreatic cancer or related treatments like U-13C-glucose. Therefore, no relevant safety information is available from these sources. ^{1 4 5 6 7}

How is Therapeutic Conventional Surgery different from other treatments for pancreatic cancer?

Therapeutic Conventional Surgery, also known as Transoral Surgical Resection, is unique because it involves a surgical approach to remove cancerous tissue, which is different from other treatments that focus on targeting the metabolic pathways of pancreatic cancer cells. This surgery may offer a direct method to physically remove tumors, whereas other treatments often aim to disrupt the cancer's altered metabolism. ^{1 3 4 5 8}

What is the purpose of this trial?

This clinical trial investigates the nutrients pancreatic cancers depend on in which to survive and the processes these tumors use (metabolism) to obtain these nutrients. 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 experiments may help researchers understand how cancer cells manage their nutrients when compared to normal pancreatic cells.

Research Team

Howard S. Hochster

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Glucose metabolic phenotype of pancreatic cancer. [2018]

2. England 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. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Metabolic reprogramming by driver mutation-tumor microenvironment interplay in pancreatic cancer: new therapeutic targets. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Employing Metabolism to Improve the Diagnosis and Treatment of Pancreatic Cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Metabolism addiction in pancreatic cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Targeting neoadjuvant chemotherapy-induced metabolic reprogramming in pancreatic cancer promotes anti-tumor immunity and chemo-response. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Robust Validation and Comprehensive Analysis of a Novel Signature Derived from Crucial Metabolic Pathways of Pancreatic Ductal Adenocarcinoma. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Metabolic Alterations in Pancreatic Cancer Progression. [2020]