ctDNA Blood Collection for Pancreatic and Liver Cancer
Recruiting in Palo Alto (17 mi)
Overseen byNadine Abi-Jaoudeh, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of California, Irvine
Disqualifiers: Coagulopathy, Low platelets, High INR, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a prospective pilot protocol investigating whether ctDNA detection be improved by sampling the cancer draining vein versus the standard practice of sampling from a peripheral vein in patients who are undergoing biopsies for hepatobiliary and pancreatic cancers.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications.
What data supports the effectiveness of the treatment ctDNA Blood Collection for pancreatic and liver cancer?
Research shows that circulating tumor DNA (ctDNA) can help detect minimal residual disease and predict treatment response in pancreatic cancer, making it a promising tool for monitoring and managing the disease. It can also provide early diagnostic information, which is crucial for improving outcomes in pancreatic cancer patients.
12345Is ctDNA blood collection safe for humans?
The research on ctDNA blood collection primarily focuses on its use as a biomarker for monitoring cancer, and there is no specific mention of safety concerns in the studies. However, since it involves a blood draw, it is generally considered safe, similar to other routine blood tests.
678910How is ctDNA Blood Collection treatment different from other treatments for pancreatic and liver cancer?
ctDNA Blood Collection is unique because it involves a 'liquid biopsy', which is a simple blood test that detects circulating tumor DNA (ctDNA) to provide diagnostic information. This approach is less invasive than traditional biopsies and can help in early detection and monitoring of pancreatic and liver cancer, potentially leading to more personalized treatment options.
34111213Eligibility Criteria
This trial is for adults over 18 with suspected or confirmed hepatobiliary or pancreatic cancers, such as liver, bile duct, ampullary, or pancreatic cancer. They must be scheduled for a biopsy and able to consent. Excluded are those who can't stay still during procedures, weigh over 375 pounds, have severe clotting issues or ascites preventing biopsy.Inclusion Criteria
I am being evaluated for liver, bile duct, or pancreatic cancer.
I am 18 years old or older.
Must be able to provide a written informed consent
+1 more
Exclusion Criteria
I weigh less than or equal to 375 pounds.
You are unable to have a blood test to check for ctDNA.
I have severe fluid buildup in my abdomen that cannot be drained or biopsied through the neck.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Biopsy and Blood Sampling
Participants undergo a biopsy procedure and blood sampling from both the cancer draining vein and a peripheral vein
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after the biopsy and blood sampling
Up to 1 year
Participant Groups
The study is testing if collecting ctDNA (circulating tumor DNA) from the vein draining the cancer site gives better results than from a standard peripheral blood draw in patients undergoing biopsies for certain abdominal cancers.
1Treatment groups
Experimental Treatment
Group I: ctDNA collection from draining and peripheral veinsExperimental Treatment1 Intervention
Patient with suspected primary hepatobiliary or pancreatic cancer undergoing a diagnostic work-up with a percutaneous or trans-jugular biopsy (standard of care) and will undergo a sampling of the cancer draining vein during their biopsy procedure with a collection of an additional 10mL of blood.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Chao Family Comprehensive Cancer Center, University of California, IrvineOrange, CA
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Who Is Running the Clinical Trial?
University of California, IrvineLead Sponsor
References
The Emerging Role of Circulating Tumor DNA in Non-Colorectal Gastrointestinal Cancers. [2023]Assays to detect circulating tumor DNA (ctDNA) have multiple clinically important applications in management of multiple types of gastrointestinal cancers. Different methodologies of ctDNA detection have varying sensitivities and potential applications in different contexts. For patients with localized cancers treated for curative intent, ctDNA detection is associated with prognosis in multiple cancer types, and persistent detection of ctDNA after surgical resection is highly concerning for minimal residual disease (MRD) and forebodes impending radiographic and clinical recurrence. CtDNA assays for comprehensive genomic profiling enable genotyping of cancers in the absence of tumor tissue data, and longitudinal testing can also characterize clonal evolution and emergence of putative resistance mechanisms upon treatment with targeted agents. These applications have proven instructive in patients with HER2-amplified gastric and esophageal cancers and in patients with FGFR2 fusion cholangiocarcinomas. In this review, we summarize data supporting the role of ctDNA as a novel predictive and prognostic biomarker and potential impacts on current management of patients with pancreatic, gastroesophageal, and hepatobiliary cancers.
Circulating tumor DNA (ctDNA) to evaluate minimal residual disease (MRD), treatment response, and posttreatment prognosis in pancreatic adenocarcinoma. [2023]Circulating tumor DNA (ctDNA) has emerged as a blood-based test with multiple utilities in oncology. In the past few years, multiple studies of varying designs, methods, and quality have emerged which show promise for ctDNA as a tool to assess response to treatment and detect minimal residual disease (MRD) across various gastrointestinal (GI) malignancies. We aim to review the current literature for ctDNA as it pertains to assessing treatment response, MRD, prognosis, and risk of recurrence for pancreatic adenocarcinoma.
Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy. [2022]Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC).
Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer. [2018]Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The "liquid biopsy" addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.
Circulating tumor DNA as a predictive marker for occult metastases in pancreatic cancer patients with radiographically non-metastatic disease. [2021]To elucidate the effectiveness of circulating tumor DNA (ctDNA) for predicting occult metastases in patients with pancreatic cancer without apparent metastases.
Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients. [2022]Cell-free circulating tumor DNA (ctDNA) in plasma has been used as a potential noninvasive biomarker for various tumors. Our study was performed to evaluate the clinical implications of ctDNA detection in patients with metastatic pancreatic cancer. First, we attempted to prospectively screen a panel of 60 genes in cell-free DNA (cfDNA) from ten metastatic pancreatic cancer patients via exome sequencing. Second, droplet digital PCR (ddPCR) was used to identify potential mutations in a cohort of 188 patients with metastatic pancreatic cancer. Finally, to preliminary evaluate the potential role of ctDNA in monitoring tumor responses following chemotherapy, we detected the presence of ctDNA in serial plasma samples from 13 metastatic pancreatic cancer patients (Clinical trial: NCT02017015). The analysis revealed five somatic mutations at BRCA2, EGFR, KDR and ERBB2 gene loci. The frequencies of ctDNA mutation at BRCA2, KDR, EGFR, ERBB2 exon17 and ERBB2 exon27 were 11.7%, 13.8%, 13.3%, 13.3% and 6.4% respectively. Univariate and multivariate analyses identified the ERBB2 exon17 mutation (p = 0.035, HR = 1.61) as an independent factor associated with overall survival among metastatic pancreatic cancer patients. Furthermore, the rate of coincident detection of ctDNA and response to treatment as assessed by CT imaging was 76.9% (10 of 13 cases), and the presence of ctDNA provided the earliest measure of treatment in 6 of 10 patients (60%). ctDNA sequencing may have clinical value for determining metastatic pancreatic cancer treatment and monitoring the tumor response.
Clinical relevance of circulating KRAS mutated DNA in plasma from patients with advanced pancreatic cancer. [2022]We used KRAS mutations to investigate the clinical relevance of circulating tumor DNA (ctDNA) measurements in patients with advanced pancreatic cancer. Fifty-three blood samples were collected from 14 prospectively recruited patients prior to chemotherapy (gemcitabine or FOLFIRINOX) and subsequently every month during treatment. Samples were processed by density centrifugation and plasma DNA isolation. A Peptide-nucleic acid-clamp PCR was then used to detect KRAS mutations (present in >90% of pancreatic cancers) as a surrogate marker for ctDNA. Plasma samples from 29 healthy individuals were analyzed as a reference group. Results were compared to conventional monitoring measures and survival data. Median follow-up time was 3.7 months (range 0.6-12.9 months). Ten (71%) patients had a positive KRAS status in the plasma samples obtained prior to chemotherapy, indicating the presence of ctDNA. Among the patients who were ctDNA-positive before chemotherapy, nine (90%) experienced disease progression during follow-up, compared to one (25%) of four ctDNA-negative patients (P = 0.01). The pre-therapy ctDNA level was a statistically significant predictor of both progression-free and overall survival (P = 0.014 and 0.010, respectively). Of the 14 patients, ten had ≥2 follow-up samples; in several of these patients, the ctDNA level changed substantially during the course of chemotherapy. Changes in ctDNA levels corresponded both with radiological follow-up data and CA19-9 levels for several patients. This pilot study supports the hypothesis that ctDNA may be used as a marker for monitoring treatment efficacy and disease progression in pancreatic cancer patients. Recruitment of more patients is ongoing to corroborate these findings.
Circulating Tumor DNA as a Clinical Test in Resected Pancreatic Cancer. [2022]Label="PURPOSE">In research settings, circulating tumor DNA (ctDNA) shows promise as a tumor-specific biomarker for pancreatic ductal adenocarcinoma (PDAC). This study aims to perform analytical and clinical validation of a KRAS ctDNA assay in a Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathology-certified clinical laboratory.
Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma. [2023]KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations.
Molecular profiling of ctDNA in pancreatic cancer: Opportunities and challenges for clinical application. [2021]Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised.
Detection of Circulating Tumor DNA in Patients with Pancreatic Cancer Using Digital Next-Generation Sequencing. [2021]Circulating tumor DNA (ctDNA) measurements can be used to estimate tumor burden, but avoiding false-positive results is challenging. Herein, digital next-generation sequencing (NGS) is evaluated as a ctDNA detection method. Plasma KRAS and GNAS hotspot mutation levels were measured in 140 subjects, including 67 with pancreatic ductal adenocarcinoma and 73 healthy and disease controls. To limit chemical modifications of DNA that yield false-positive mutation calls, plasma DNA was enzymatically pretreated, after which DNA was aliquoted for digital detection of mutations (up to 384 aliquots/sample) by PCR and NGS. A digital NGS score of two SDs above the mean in controls was considered positive. Thirty-seven percent of patients with pancreatic cancer, including 31% of patients with stages I/II disease, had positive KRAS codon 12 ctDNA scores; only one patient had a positive GNAS mutation score. Two disease control patients had positive ctDNA scores. Low-normal-range digital NGS scores at mutation hotspots were found at similar levels in healthy and disease controls, usually at sites of cytosine deamination, and were likely the result of chemical modification of plasma DNA and NGS error rather than true mutations. Digital NGS detects mutated ctDNA in patients with pancreatic cancer with similar yield to other methods. Detection of low-level, true-positive ctDNA is limited by frequent low-level detection of false-positive mutation calls in plasma DNA from controls.
Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer. [2021]Currently available serum biomarkers for pancreatobiliary cancers lack sensitivity and specificity and ultimate diagnosis still requires invasive procedures for histological confirmation. The detection of tumor-specific genetic aberrations with utilization of cell free DNA (cfDNA) is a less invasive approach than traditional tissue biopsies; however, it has not been implemented into clinical routine. In this study, we investigated bile as a liquid biopsy source in pancreatobiliary cancers and compared its potential as cell-free DNA source to plasma. Blood (n = 37) and bile (n = 21) samples were collected from patients affected by pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (CCA) or with non-malignant biliary obstructions (blood n = 16; bile n = 21). Panel-based next generation sequencing (NGS) and digital droplet PCR (ddPCR) were applied for tumor mutation profiling. NGS results from matched tumor tissues (n = 29) served as comparison. Sequencing of cfDNA from bile resulted in detection of 96.2% of the pathogenic tumor mutations found in matched tissue samples. On the other hand, only 31.6% of pathogenic tumor mutations found in tissue could be detected in plasma. In a direct comparison, only half of the mutations detected in bile cfDNA were concordantly detected in plasma from the same patients. Panel NGS and ddPCR displayed comparable sensitivity. In conclusion, bile is a suitable source of cfDNA for the diagnosis of pancreatobiliary cancer and performs more reliably than plasma. Although primary diagnosis still requires histologic confirmation, bile-derived cfDNA could offer an alternative if tissue sampling is not feasible and might allow less invasive disease monitoring.
Circulating tumour DNA: a challenging innovation to develop "precision onco-surgery" in pancreatic adenocarcinoma. [2023]Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the third leading cause of cancer-related mortality within the next decade. Management of PDAC remains challenging with limited effective treatment options and a dismal long-term prognosis. Liquid biopsy and circulating biomarkers seem to be promising to improve the multidisciplinary approach in PDAC treatment. Circulating tumour DNA (ctDNA) is the most studied blood liquid biopsy analyte and can provide insight into the molecular profile and individual characteristics of the tumour in real-time and in advance of standard imaging modalities. This could pave the way for identifying new therapeutic targets and markers of tumour response to supplement diagnostic and provide enhanced stratified treatment. Although its specificity seems excellent, the current sensitivity of ctDNA remains a limitation for clinical use, especially in patients with a low tumour burden. Increasing evidence suggests that ctDNA is a pertinent candidate biomarker to assess minimal residual disease after surgery but also a strong independent prognostic biomarker. This review explores the current knowledge and recent developments in ctDNA as a screening, diagnostic, prognostic and predictive biomarker in the management of resectable PDAC but also technical and analytical challenges that must be overcome to move toward "precision onco-surgery."