Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Julia Sidenius Johansen, MD, DMsc

Inna Markovna Chen, MD

No validated biomarkers to identify PC at an early stage and to predict treatment outcomes in the individual patient exist. The objective of the present study is to find diagnostic, prognostic and predictive biomarkers.

The overall survival of patients with pancreatic cancer (PC) is dismal and has only improved slightly during the last decades primarily due to combination chemotherapy. Early detection of PC is difficult and less than 25% of all PC patients are operated. No validated biomarkers to identify PC at an early stage and to predict treatment outcomes in the individual patient exist. The objective of the present study is to find diagnostic, prognostic and predictive biomarkers, which can be used to 1) diagnose PC early in the disease course with high specificity and sensitivity, 2) improve prognostication, or 3) predict and monitor treatment effectiveness and tolerability for the individual patient.

BIOPAC is an observational and translational open cohort study with prospective collection of biological materials and clinical data in patients with PC treated in routine care and also patients who were suspicious for malignancy in the pancreas but then operated without evidence of malignancy. Patients contribute with blood samples (i.e. serum, EDTA plasma and buffy coat, and blood in PAXgeneRNA tubes) before operation or start of adjuvant or palliative chemotherapy and during treatment with blood sampling before 2. cycle of chemotherapy and longitudinally every time of CT scan until disease progression. This schedule is repeated if patients are treated with subsequent lines of chemotherapy. The patients are followed until death. Demographics, disease characteristics, comorbidities and lifestyle factors are registered at inclusion; weight and performance status at each treatment cycle; routine blood tests (i.e. haematology, creatinine, liver enzymes, bilirubin, carbohydrate antigen 19-9, C-reactive protein); type of operation; types of chemotherapy and number of cycles given; date of disease recurrence in operated patients; date of disease progression for each line of chemotherapy; and date of death. Biomarker analyses will include a range of molecules with different characteristics such as DNA, Single Nucleotide Polymorphism (SNPs), RNA, microRNA, proteins and metabolites. Data will be analysed using appropriate methods and statistical analyses.

Blood samples and tissue from primary tumor and/or metastasis

BIOmarkers in Patients With Pancreatic Cancer ("BIOPAC")

BIOmarkers in Patients With PAncreatic Cancer (BIOPAC) - Can They Provide New Information of the Disease and Improve Diagnosis and Prognosis of the Patients?

Biomarker analyses include, but are not limited to a range of molecules with different characteristics such as DNA, Single Nucleotide Polymorphism (SNPs), RNA, microRNA, proteins and metabolites.

Inna Chen, MD

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Triple Negative Breast Neoplasms

Pathologic Complete Response

Breast Diseases

Skin Diseases

Initially, patients will be analyzed in a single group. After determining the status of the biomarkers, the patient sample will be divided into specific groups for comparative purposes.

Jesse L da Silva, MD

A single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival.

Background/Rationale: Triple negative breast cancer (TNBC) is known to be a heterogeneous disease, and different molecular sub-classifications are proposed based in specific biomarkers as immunohistochemical (IHC) expression of the androgen-receptor (AR), Epidermal growth Factor Receptor (EGFR), Cytokeratin 5/6 (CK5/6), Cytokeratin14 (CK14), Cytokeratin 17 (CK17), clusters of differentiation 117 (CD 117), p53, Ki67 level, Programmed cell death-ligand 1 (PD-L1) and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes (PD-1+, FOXP3+, CD 4+ or cluster designation 8 (CD8 +), CD 3+, cluster of differentiation 56 (CD56+), cluster designation 68 (CD68+) or CD 14+). Predicting response and survival to neoadjuvant treatment of locally advanced triple-negative breast cancer remains a major challenge. Many doubts still prevail over the role of new biomarkers in predicting different outcomes for tumors with the same stage and morphological characteristics.

Objectives and Hypotheses:

Primary objective: To evaluate the association of the intratumoral lymphocytic infiltrate (TILs) status profile in the core biopsy with complete pathological response (CPR) outcomes to neoadjuvant chemotherapy and progression-free survival (PFS). Secondary objectives: To evaluate the association of the others biomarkers expression profile and the quality of TILs with PFS and CPR. To determine the prevalence of a large immunohistochemical panel (AR, EGFR, CK5/6, CK14, CK17, CD 117, p53, Ki67 level, PD-L1 and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes PD-1+, FOXP3+, CD 4+ , CD8 +, CD 3+, CD56+, CD68+ and/or CD 14+), before and after neoadjuvant chemotherapy. To determine if the negativation of biomarkers after the systemic treatment is associated with CPR and PFS.

Methods:

Study design: A cohort with retrospective data collection and sectional analysis of pathological material.

Data Source(s): Medical records and pathological material. Study Population: Women with locally advanced triple negative breast cancer consecutively enrolled at Brazilian National Cancer Institute (INCA) submitted to neoadjuvant treatment and subsequently operated.

Exposure(s): Status of specified biomarkers. Outcome(s): Complete Pathologic Response and Progression free Survival and Sample Size Estimations: With a type I error of 5% and study power of 80%, it is estimated that 155 patients are needed.

Statistical Analysis: Statistical analysis will be performed using SPSS (version 18.0 for windows, statistical package for social science (SPSS) Inc., Chicago, IL). Survival curves will be constructed using the Kaplan-Meier method.

Paraffin-embedded Hematoxylin \& Eosin (H \& E) core biopsy/early biopsy and surgical specimens previously analyzed in the Department of Patology of the Brazilian National Cancer Institute (INCA) will be doubly reviewed by two pathologists in our study for histological grade (Scarff-Bloom-Richardson method, modified by Elston and Ellis), histological type (according to World Health Organization, 2012), presence of carcinoma component "in situ", angiolymphatic invasion, perineural infiltration, presence of lymphocytic inflammatory infiltrate.

Triple-negative Breast Cancer: a New Perspective on Biomarkers

Triple-negative Breast Cancer: a New Perspective on Predictive and Prognostic Biomarkers

The first event defined as local recurrence or distant relapse, or death, whichever come first.

To determine the clinical response rate in patients with palpable disease.

To compare overall objective response rate in both treatment groups.

To determine predictive markers for sensitivity and resistance to chemotherapy.

To determine prognostic markers for progression free survival after neoadjuvant chemotherapy and surgery.

Instituto Nacional de Cancer, Brazil

Colorectal Neoplasms

Recurrence

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Disease Attributes

patients with any of the four genes hypermethylated

patients with none of the four genes hypermethylated

detecting the methylation status of colorectal cancer specimen

DNA methylation detection

Yanxin Luo, MD,PhD

Du Cai, MD

Yanxin Luo, PhD,MD

This study aims to evaluate the predictive value of a four-gene methylation assay called Guangzhou Panel in early-stage colorectal cancer. Patients will be divided into two groups: high risk group and low risk group. The primary endpoint is 5 year disease free survival (DFS).

The current risk stratification system defined by clinicopathological features does not identify the risk of disease recurrence in patients with early-stage colorectal cancer (CRC) with optimal accuracy. The investigators aimed to investigate whether the epigenetic alterations could serve as novel prognostic biomarkers that would improve the accuracy of the current primary tumor, regional nodes, metastasis (TNM) staging system.

In the current study, the Investigators have analyzed the genome-wide methylation status of cytosine-phosphate-guanosine (CpG) sites using Infinium MethylationEPIC array in primary tumor and adjacent normal samples from 23 recurrent and 22 recurrence-free stage I and II CRC patients to identify potential methylation markers for disease-free survival (DFS). The prognostic value of the candidate biomarkers has been evaluated in a training cohort (n=174) and an independent validation cohort (n=267), and is to be validated in a prospective cohort (estimated n=287).

Comprehensive data analysis identified a subset of methylated CpG loci that associated with a high risk of recurrence. Methylated CpGs in four genes were significantly associated with DFS in multivariate analysis in both training and validation cohort. Moreover, Hypermethylated Genes Counts panel using these four markers showed a higher prognostic value than any clinicopathological factor, current molecular biomarkers or single methylated CpG marker alone in the training and validation cohorts. This four-gene methylation assay is defined as Guangzhou Panel.

The investigators aim to conduct a prospective observational study to evaluate the predictive value of Guangzhou Panel in early-stage colorectal cancer. A total of 287 patients with pathologically verified stage I-II CRC and underwent surgical resection are expected to be recruited in our study. These patients will be divided into high-risk group and low-risk group and will be followed up at least 5 years. The primary endpoint is 5-year disease free survival (DFS). The prognostic strength of candidate biomarkers was adjusted in multivariate Cox regression models including multiple biomarkers and clinicopathologic variables.

tissue specimen from colorectal cancer patients who underwent radical resection

The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer

Our DNA methylation panel is applying for patent protection, therefore we plan to keep the data private for the time being.

the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer

Sixth Affiliated Hospital, Sun Yat-sen University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Renal Cell

Neoplastic Cells, Circulating

Kidney Neoplasms

Carcinoma

Neoplasm Metastasis

Neoplastic Processes

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Renal Cell Carcinoma

None- observational study

Alison L Allan, PhD

Circulating tumor cells (CTCs) have prognostic value in several tumor types, and increasing evidence suggests that molecular characterization of CTCs can serve as a "liquid biopsy" to understand and address treatment resistance. The goal of this proposal is to demonstrate that CTCs can be accurately enumerated and characterized in metastatic clear cell renal cancer (CCRC) and can serve as prognostic/predictive biomarkers to improve treatment. The challenge surrounding CTC analysis in CCRC is that most CTC technologies (including the clinical gold-standard CellSearch®) depend in epithelial markers such as EpCAM that are expressed at low or heterogeneous levels in CCRC. Members of the research team have developed a novel CTC microfluidic technology that can effectively detect CTCs that are completely undetectable by CellSearch® because of very low EpCAM expression, as well as allowing for CTC recovery for downstream molecular characterization. The goal of this proposal is therefore to test the hypotheses that (1) The microfluidics CTC technology will have better sensitivity/specificity relative to the CellSearch in metastatic CCRC; and (2) Enumeration of CTCs in metastatic CCRC patients (n=66) will have prognostic value, while molecular characterization of CTCs for expression of biomarkers (VHL, VEGF, mTOR, HIF1/HIF2, AKT) related to CCRC etiology will be predictive of response/resistance to targeted therapies. Although CCRC is relatively uncommon, the lack of established adjuvant treatments and high cost of targeted therapies in the palliative setting makes the search for new prognostic/predictive biomarkers an important clinical goal.

Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer

Prospective Validation of Circulating Tumor Cells (CTCs) and Circulating Endothelial Cells (CECs) as Prognostic Biomarkers in Clear Cell Renal Cancer

For comparison of the 2 CTC platforms, a Bland-Altman plot will be constructed. This plot is superior to standard correlation statistics in that it assesses agreement rather than association. Initially we will use a Chi-Square test to compare the 2 methods at a cutoff point of ≥5 versus \<5 CTCs/7.5mL, with simple comparison of PFS at this level. As the cut-off point may not be the same for each method, we will also compare the methods using simple 2X2 contingency tables.

Survival analysis will be performed by Kaplan Meier and significance analysis will use the log-rank test. Cox multivariate analysis will be performed to look at the number and molecular characteristics of CTCs as independent prognostic parameters of survival.

Radiological assessment of disease status will be carried out as standard-of-care and subjected to correlative analysis relative to CTC status, PFS and OS.

CTCs will be recovered from the microfluidics device and subjected to molecular characterization for expression of markers related to angiogenesis and hypoxia.

CTCs will be enumerated on both the CellSearch and the novel microfluidic device.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BIOmarkers in Patients With Pancreatic Cancer ("BIOPAC")	NCT03311776	Pancreatic Canc...		19 Years -	Herlev Hospital
Triple-negative Breast Cancer: a New Perspective on Biomarkers	NCT03539965	Triple Negative... Triple Negative...		18 Years - 80 Years	Instituto Nacional de Cancer, Brazil
The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer	NCT03923335	Colorectal Neop...	DNA methylation...	40 Years - 70 Years	Sixth Affiliated Hospital, Sun Yat-sen University
Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer	NCT02499458	Clear Cell Rena... Circulating Tum... Circulating End... Prognostic Biom... Predictive Biom...	None- observati...	18 Years -	Lawson Health Research Institute
Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer	NCT02499458	Clear Cell Rena... Circulating Tum... Circulating End... Prognostic Biom... Predictive Biom...	None- observati...	18 Years -	Lawson Health Research Institute
The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer	NCT03923335	Colorectal Neop...	DNA methylation...	40 Years - 70 Years	Sixth Affiliated Hospital, Sun Yat-sen University

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