Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Subjects with known colorectal cancer (i.e. AJCC/UICC stages 0, I, II, and III) who provide plasma at least 7 days after diagnosis by colonoscopy, but prior to surgery or treatment

Prospectively enrolled subjects reporting for screening colonoscopy who provide a blood sample up to 2 weeks prior to bowel prep and prior to colonoscopy. We accept all subjects who meet the institutional criteria as average risk subjects referred for a screening colonoscopy for colorectal cancer, including subjects undergoing a colonoscopy as a follow-up to a positive (non-colonoscopic) test

Analysis of DNA methylation status for Septin9 and additional biomarkers

Epi proColon

Theo deVos, PhD

The objective of this Clinical Sample Collection Study is to develop a biobank of appropriately collected plasma samples from colorectal cancer patients (i.e. AJCC/UICC stages 0, I, II, III) prior to therapeutic intervention, and from people reporting for colorectal cancer screening by colonoscopy, prior to bowel preparation.

The objective of this Clinical Sample Collection Study is to develop a biobank of appropriately collected plasma samples from colorectal cancer patients (i.e. AJCC/UICC stages 0, I, II, III) prior to therapeutic intervention, and from people reporting for colorectal cancer screening by colonoscopy, prior to bowel preparation. Samples in the colorectal cancer biobank will be used to: 1) assess the clinical performance of novel biomarkers for colorectal cancer screening; 2) develop improved processing workflows for the Epi proColon® test; 3) develop an automated Epi BiSKit workflow.

Plasma-based Colorectal Cancer Screening Research & Development

Clinical Sample Protocol for Plasma-based Colorectal Cancer Screening Research & Development

DNA methylation status of Epi proColon and biomarker panel

Epigenomics, Inc

Rare Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Marc SANSON, MDPhD

The recurrent mutation IDH1Arg132His leads to the cellular accumulation of D-2-hydroxyglutarate (2-HG), thus representing a diagnostic marker (this change is almost specific for gliomas) and prognostic (mutated gliomas have longer survival) of interest.

The main objective is to identify the patients with IDH1 mutated glioma by three complementary approaches -genetic (identification of IDH1 mutation in plasmatic DNA), biochemical (2-HG dosage in the urine of patients) and radiological (2-HG

Our preliminary results indicate an extremely high amount of D-2HG in gliomas and CSF of the patients, and therefore the possibility to detect its presence by spectro-MRI, and to establish a non-invasive diagnosis of glioma with IDH1 mutation. Our goal is to identify and quantify by high-field MRI spectroscopy the presence of D-2HG to identify gliomas with IDH1 mutation. In parallel, we developed a technique for selective amplification of the mutated form of IDH1 (COLD PCR): by combining this technique with digital PCR, we already are able to detect IDH1 mutation from free plasma DNA with a sensitivity of 58% and a specificity of 100%. At the same time we have shown that D-2HG levels in urine of patients correlate with the status of the tumor IDH1.

The main objective is to identify using this triple approach (detection of the mutation on plasma DNA detection, detection of urinary D-2HG, detection of tumor D-2HG by spectro-MRI) patients with IDH1arg132His mutation, the secondary objective is to evaluate the value of these markers for patients follow-up and for differentiating recurrence from treatment induced damage. 40 patients with grade II and grade III gliomas (20 mutated, 20 non mutated) will be included and followed up for one year (five measurements are planned).

The first interest is diagnostic: the presence of the IDH1Arg132His mutation allows the diagnosis of glioma. This information is particularly valuable in patients not amenable to biopsy, because of the location of the tumor considered at risk, the general condition of the patient or the co-morbidities and medications. We hope also with these parameters to better monitor patient's follow-up, and to have a new method to differentiate tumor recurrence and radionecrosis or post-radiation leukoencephalopathy.

Plasma samples containing free DNA fragments Urine

Non Invasive IDentification of Gliomas With IDH1 Mutation

Non Invasive IDentification of Gliomas With IDH1 Mutation by Free Plasmatic DNA Analysis, 2-hydroxyglutarate Dosage in the Urines and 2-hydroxyglutarate Detection by Brain SPEctro-MRI: Diagnostic and Follow-up Application (IDASPE)

Institut National de la Santé Et de la Recherche Médicale, France

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Behaviors and Mental Disorders

Adenoma

Prostatic Hyperplasia

Hyperplasia

Urinary Incontinence

Enuresis

Nocturnal Enuresis

Urination Disorders

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Lower Urinary Tract Symptoms

Urological Manifestations

Behavioral Symptoms

Elimination Disorders

Mental Disorders

Psychotic Disorders

Prostatic Diseases

Genital Diseases

Genital Diseases, Male

Anticoagulants

All Drugs and Chemicals

Imidacloprid

This technique consists of an endoscopic intervention, through the natural route (urethra).

This is a recent and difficult technique of endoscopic prostate enucleation, requiring a greater learning curve for the operators compared to PLASMA. The principle remains the same technically as the PLASMA procedure, the energy used is not electrical energy, but a laser.

Once the adenoma has been enucleated, it can only be removed by a morcellator (additional material) which can lead to complications such as bladder perforation. This is a blade that rotates in a tube that has to cut the adenoma once it has been freed from the prostate when it is in the bladder and it can happen that this blade catches on the bladder wall and causes a bladder wound or even a perforation.

The aim is to remove the prostatic adenoma by enucleation, i.e. to pass through the plane between the adenoma and the prostatic capsule, as opposed to resection, which also consists of removing the adenoma, but by making small cuts in the prostatic tissue, without necessarily reaching this anatomical plane between the adenoma and the capsule. This means removing less adenoma and therefore increasing the risk of adenomatous regrowth in the long term or obtaining worse results than enucleation in the short to medium term.

The other advantage of using this approach is that it reduces intra- and post-operative bleeding and does not require the systematic discontinuation of anti-aggregating or anticoagulant treatments prior to the operation. The field of indications is thus potentially enlarged.

PLASMA

Soria Jérémie, MD

Benign prostatic hypertrophy or prostatic adenoma is a benign tumour that develops in the central part of the prostate. Prostatic adenoma can result in the progressive appearance of a difficulty in evacuating the bladder or frequent urges to urinate and other complications (lithiasis, haematuria, urinary retention, etc.). Surgery is indicated when medical treatment is no longer effective and in the case of complications. The endoscopic techniques for treating prostate adenoma, PLASMA and HOLEP, are recognised and recommended by the French Association of Urology and the European Association of Urology (EAU) as Gold Standard techniques in view of the good results reported in the literature, the low rate of complications compared to the other techniques, and the reduced hospitalisation rate. For prostate volumes less than 80cc, there is no difference between HOLEP and Bipolar Plasma Enucleation of the Prostate (BTUEP) in terms of International Prostate Symptom Score (IPSS), Qmax, and reoperation rate at 12 months. The surgeon's experience is the most important factor influencing the risk of complications for HOLEP. Urinary incontinence after HOLEP according to Houssin et al. is 14.5% at 3 months and 4.2% at 6 months, the risk factors identified were surgeon experience and the existence of diabetes. Comparative evaluation of the two techniques is less frequent, hence the interest of our prospective and multicentre study. In this study, the investigators hope to demonstrate a better outcome of the PLASMA technique in terms of post-operative residual urinary incontinence.

Benign prostatic hyperplasia or prostatic adenoma is a benign tumour that develops in the central part of the prostate. It usually affects men over the age of 50, with the incidence of the disease increasing with age. Prostatic adenoma may result in the progressive appearance of bladder weakness or frequent urination and other complications (lithiasis, haematuria, urine retention, etc.).

Surgery is indicated when medical treatment is no longer effective and in the case of complications.

Among the surgical interventions, several techniques are currently offered to the patient:

* transurethral monopolar resection
* transvesical adenomectomy
* HOLEP laser enucleation of the prostate
* Bipolar resection and enucleation using the Bipolar Plasma Enucleation of the Prostate (BTUEP) technique, also known as "PLASMA".

Transurethral monopolar resection is considered an obsolete technique by the learned societies, in particular because of the risk of transurethral resection of the prostate syndrom (vital risk for the patient in the event of reabsorption of the peroperative glycocoll washing liquid), the per and postoperative haemorrhagic risk, especially in patients who are on anticoagulants and/or anti-aggregants and who cannot be stopped for the prostatic procedure.

Transvesical adenomectomy has a higher bleeding risk due to the fact that it is performed in open surgery, which is much more invasive. There is a transfusion rate of 7-14%. The rate of urinary incontinence can be as high as 10% and the rate of urethral stenosis 6%.

Compared to BTUEP or HOLEP, HOLEP has a longer operating time, longer catheterisation and hospitalisation time and a higher transfusion rate for transvesical adenomectomy.

Adenomectomy should therefore only be offered if the centre has neither HOLEP nor BTUEP according to European recommendations.

The new endoscopic techniques for treating prostate adenoma, PLASMA and HOLEP, are recognised and recommended by the French Association of Urology and the European Association of Urology (EAU) as Gold Standard techniques in view of the good results reported in the literature, the low rate of complications compared with the other techniques described above, and the reduced hospitalisation rate.

For prostate volumes less than 80cc, there is no difference between HOLEP and BTUEP in terms of IPSS, Qmax, and reoperation rate at 12 months.

Compared to conventional transurethral resection of the prostate, there was a significant improvement in International Prostate Symptom Score (IPSS), quality of life (QoL), and Qmax for the BTUEP technique. These results are valid at 36, 48 and 60 months. BTUEP was also superior in terms of haemoglobin loss, duration of irrigation, duration of catheterisation and duration of hospitalisation, as well as a reduction in the post-operative retention rate and the transfusion rate. There is no greater risk of incontinence with BTUEP than with transurethral resection of the prostate.

For HOLEP, there was no significant difference in Qmax or reoperation rate compared to MTURP. Compared to BTUEP, there was no significant difference in IPSS, QOL, and Qmax according to two meta-analyses. Functional outcomes at 7 years follow-up between HOLEP and monopolar transurethral resection of the prostate (MTURP) are comparable and HOLEP has an advantage in catheterisation time, hospitalisation, loss of haemoglobin, no more urethral strictures or urge incontinence.The experience of the surgeon is the most important factor influencing the risk of complications in HOLEP.

Urinary incontinence after HOLEP according to Houssin et al. is 14.5% at 3 months and 4.2% at 6 months, the risk factors identified were surgeon experience and the existence of diabetes.

In a comparative study of HOLEP and PLASMA, 19% of incontinence was found at 3 months for HOLEP against 6% for PLASMA.

Other a study found lower rates of 5.7% for HOLEP. Based on these data, the functional outcomes of PLASMA and HOLEP are comparable. However, comparative evaluation of the two techniques is less frequent in studies which are generally retrospective or monocentric, hence the interest of our prospective and multicentric study.

By comparing two reference techniques of prostatic enucleation, HOLEP and PLASMA, the investigators hope to demonstrate in this study a better result of the PLASMA technique in terms of post-operative residual urinary incontinence. If this is demonstrated, PLASMA could overtake HOLEP, with a significantly lower material cost and a reduced learning curve.

Observational Study to Compare Two Prostate Laser Enucleation Techniques in Terms of Urinary Incontinence

Observational Study to Compare Two Prostate Laser Enucleation Techniques (Photo-vaporization of the Prostate (PLASMA) Versus HoLEP) in Terms of Overall Post-operative Urinary Incontinence

Pad weight testing during 3 consecutive days

Duration of urinary catheterisation (minutes)

International Prostate Symptom Score - Quality of life dimension

Recording of prescriptions for anti-cholinergic treatments

Record of re-hospitalizations for hematuria with bladder clotting

Collection of acute urine retention, falls, bedsores, urinary tract infections, urinary incontinence

Elsan

Pierre LAURENT-PUIG

Cancer is a DNA disease characterized by the presence of genetics alterations in cancer cells.

The recent studies underline that these recurring alterations must be considered as a good molecular marker. In fact, they could use for tumor DNA detection in different biological fluids.

So, the main purpose is to define the presence of circulating tumor DNA in the patients plasma with colorectal cancer, by the presence of mutation (KRAS, NRAS, BRAF, APC, TP53 and MIRCOSATELLIE instability).

These molecular analysis will be done both in tumor and plasma samples,

This trial allows to characterize the prognostic value of circulating tumoral DNA presence in colorectal cancer.

Two major issues appear in improving the prognosis of cancer patients, the first is early detection and the second is the risk of recurrence or the early diagnosis of recurrence in order to propose the most appropriate treatment for patients.

Cancer is a DNA disease that is characterized by the acquisition by the tumor cell during carcinogenesis of a number of recurrent genetic alterations. The development of molecular tools that can easily characterize these abnormalities specific to tumor cells, allows us to consider their use in clinical practice. These genetic alterations could represent useful molecular markers for detecting the presence of tumor DNA in various biological fluids including plasma of cancer patients. This circulating tumor DNA, whose nature is confirmed by the similarity of genetic alterations with those observed from DNA extracted from tumor cells of the patients, represents a molecular marker of cancer available from a single sample and could be an alternative to the use of more conventional markers such as CEA. We propose in this study to confirm the predictive value on the risk of recurrence or metastasis of circulating tumor DNA in plasma of patients with colorectal cancer from a cohort study (250 patients with non-metastatic colorectal cancer (Stage II and III). This is a multicenter prospective study. The cohort of patients will be followed for a minimum period of 36 months. A biological analysis of the tumor in search for the main genetic alterations of colorectal cancer cells will be made (KRAS, NRAS, TP53, BRAF and APC mutations as well as the presence of a microsatellite instability). These same genetic alterations will be sought on a plasma sample taken before surgery and during follow-up (9 samples in total). The objectives of this study will be 1/to assess the prognostic value of the presence of circulating tumor DNA in plasma, by searching for an association between the risk of and the presence of genetic alteration in the plasma of these patients, 2/to search for a relationship between initial rate of circulating tumor DNA and the risk of local recurrence,3/ to characterize the relationship between the type of alterations in the plasma at the initial diagnosis of circulating tumor DNA and the risk of recurrence 4/ to assess during the follow-up the prognostic value of the occurrence of tumor circulating DNA.

Presence of Circulating Tumor DNA in Colorectal Cancer

Search for the Presence of Genetic Alteration in the Plasma of Patients With Stage II-III Colorectal Cancers: Prognosis Impact

Assistance Publique - Hôpitaux de Paris

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Nerve Sheath Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neurofibromatosis

Neurofibromatosis Type 1

patients who are seen by oncologists and who are willing to donate an extra blood sample when blood is taken routinely

patients, who have neurofibromatosis type 1 and who have developped an MPNST,donating a blood sample

Eric Legius, MD PhD

Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant disorder, caused by heterozygous mutations of the NF1 tumor suppressor gene (chr.17q11.2). One of the main clinical features is the development of benign and malignant tumors. The most common benign tumors in these patients are tumors of the peripheral nerve, named neurofibromas. Every NF1 patient has a life time risk of 8-13% to develop a malignant peripheral nerve sheath tumor (MPNST) starting from a pre-existing neurofibroma. MPNSTs lead to a bad prognosis for the patient, with an overall five-year survival of less than 25%. Complete resection is the standard treatment, but this is often difficult due to the size of the tumors and the location on important nerves, moreover the tumor is frequently metastatic at the time of diagnosis. For MPNSTs, like for other cancers, the extent and the spread of the disease at time of diagnosis is an important factor in determining treatment outcome. In this regard, the analysis of tumor derived cell-free circulating DNA in plasma of NF1 patients would open up the possibility to diagnose and monitor the development and progression of MPNSTs using a small blood sample. In cooperation with P. Schöffski (UZLeuven), we plan to collect blood samples from cancer patients to optimize the DNA extraction procedure starting from plasma samples. It is known that patients with cancer have a higher amount of free circulating DNA in plasma than individuals without cancer and therefore we want to optimize the DNA extraction procedure on plasma from patients with cancer. In the meantime, matching MPNST and plasma samples from NF1 patients will be collected and sent to us from the University of Eppendorf (Victor Mautner) to optimize the array CGH protocol for the detection of copy number changes in plasma DNA of NF1 patients with MPNSTs.

Introduction Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder occuring in 1 out of 3500 living newborns. The disease is caused by heterozygous mutations of the NF1 gene, located on chromosome 17q11.2. The NF1 gene encodes the tumor suppressor neurofibromin, a negative regulator of the RAS oncogene. Clinically, NF1 patients have café-au-lait maculae, freckling, Lisch nodules and neurofibromas. Cognitive problems, bone lesions and optic pathway gliomas are also common in these patients.

Neurofibromas are benign neoplasms of the peripheral nerve sheath, which can appear anywhere in the body of NF1 patients. Neurofibromas are composed of different cell types like Schwann cells, fibroblasts, mast cells and perineurial cells. If in Schwann cells of NF1 patients the wild-type NF1 allele is inactivated, a neurofibroma will be formed. There are 3 types of neurofibromas: cutaneous, subcutaneous and plexiform. Cutaneous neurofibromas appear during adolescence as isolated nodules in or under the skin, respectively. Plexiform neurofibromas are congenital and can spread along a large segment of a peripheral nerve. Subcutaneous neurofibromas are discrete nodules located on peripheral nerves and the timing of their origin is not known, but they are probably also prenatal in origin.

Every NF1 patient has a life time risk of 8 to 13% to develop a malignant peripheral nerve sheath tumor (MPNST). This risk is even twice as high for a subpopulation of NF1 patients, namely patients with an NF1 microdeletion. MPNSTs are difficult to diagnose in early phase because of the large number of tumors and diverse locations often seen in these patients. These tumors infiltrate easily in surrounding tissue and frequently give rise to metastases. At this moment, the only available treatment is surgical removal of these MPNSTs. Complete resection is often difficult due to the size of the tumors and the location on important nerves and the fact that the tumors are frequently already metastasized at diagnosis. The five-year survival of patients with MPNSTs is less than 25%. For MPNSTs, like for other cancers, the extent and the spread of the disease at time of diagnosis is an important factor in determining treatment outcome. In this regard, tumor markers have been developed to screen for tumors, but only a subset of cancers secrete specific proteins that can be used as a marker. An increasing interest grew in new markers like circulating nucleic acids. The detection of cell-free circulating nucleic acids in plasma, serum and other body fluids of healthy and diseased individuals opened up the possibility to diagnose and monitor the disease, which might also be applicable to NF1 patients with MPNSTs. The presence of extracellular circulating nucleic acids in the blood of healthy and sick persons was first described by Mandel and Métais in 1948. In 1977 the group of Leon was the first to quantify cell-free DNA in serum. They found that cancer patients tended to have elevated levels of circulating DNA compared to healthy control individuals, and that the amount of DNA was even bigger in patients with metastases compared to localized disease, but nothing was known about the origin of the DNA. Significant progress in plasma/serum DNA research was made, when the presence of tumor-associated microsatellite alterations was reported in the plasma and serum of cancer patients. According to these findings, it has been suggested that the circulating DNA could have potentials for the diagnosis and prognosis of malignancies. Still, the mechanism of DNA release is not fully clarified, and different hypotheses have been suggested. A first hypothesis that the circulating DNA originates from DNA leakage due to necrosis or apoptosis of tumor cells, became controversial when it was reported that the DNA level decreased after radiotherapy. Another hypothesis about micrometastases was also rejected because the number of cells in plasma didn't match the amount of circulating DNA. A third hypothesis is the spontaneous and active release of tumoral DNA in the blood by proliferating cells. However there is no convincing explanation for the latter mechanism.

Research protocol A first part of the study will be the optimization of the technique of DNA extraction from plasma. Different DNA extraction methods described in the literature will be tested on samples collected in cooperation with Prof. Dr. Patrick Schöffski (UZLeuven). When blood is taken from cancer patients for routine testing, an additional 5 mL (in EDTA tube) will be available for our experiments. Blood samples will be collected within a few hours after sampling and processed within 24 hours in our lab (lab for neurofibromatosis research). The blood samples will be centrifuged at 1600 rpm for 10 minutes. The supernatant plasma will be collected, without disturbing the buffy coat, and re-centrifuged at 13000 rpm for 10 minutes to remove particles. The supernatant plasma will be aliquoted into 0.5 mL volumes. The samples will be stored at -80°C until further use. Per patient, different aliquots will be extracted using different methods, like phenol-chloroform extraction and commercial kits, according to the literature. Genomic reference DNA will be extracted from the buffy coat using phenol-chloroform extraction. Depending on the type of DNA extraction, we expect differences in quantity and quality of the DNA. The method with the highest yield and best DNA quality will be chosen to extract DNA from plasma of NF1 patients with MPNSTs.

Second part of this work will be the optimization of the microarray experiment using plasma DNA. Plasma samples from NF1 patients with MPNSTs will be collected in collaboration with the group of Victor Mautner from the Eppendorf University in Germany. Direct processing of blood samples will be done in Germany and frozen buffy coats and plasma aliquots will be sent to Leuven in an encoded way. Together with the buffy coats and plasma, frozen tissue of the patients MPNST will be sent as well. DNA from the tumor will be extracted using phenol-chloroform extraction. Microarray CGH will be performed on both the tumor and the plasma DNA with buffy coat DNA as reference to exclude copy number variable regions from the list of copy number changes. The array profiles of the plasma DNA will be checked for the tumor-related copy number changes. In that way, the array protocol can be further optimized in order to detect tumor specific copy number abnormalities in the cell-free DNA from plasma.

This study is performed by Eline Beert, PhD student in the lab for neurofibromatosis research, and Radost Ratcheva, a master thesis student in the lab of neurofibromatosis research, as part of achieving the degree of 'Doctor in Biomedical Sciences' and 'Master in Biomedical Sciences', respectively, with Prof. Dr. Eric Legius as promotor and main researcher. Only the Katholieke Universiteit Leuven and the UZ Leuven, but no commercial partners (like companies) will participate in this study. The results obtained from the described experiments have to be considered as pure scientific information and none of it will be reported to the patients.

The blood samples of the UZLeuven cancer patients will only be used to optimize the DNA extraction procedure, the extracted DNA will be quantified but it will not be further analyzed and will be destroyed afterwards.

Microarray CGH Analysis of Circulating Tumoral Plasma DNA in NF1 Patients With MPNSTs

Analysis of Circulating Tumor DNA in Plasma of Neurofibromatosis Type 1 Patients With MPNSTs Using Microarray CGH

KU Leuven

Eric Legius

Herbal and Botanical

Cola

The group is to include at least 1000 individuals who are at high risk for the development of cancer. Risk is assessed through the completion of a clinical history questionnaire. Examples of such subjects include those with known hereditary cancer syndrome pathogenic variants without a diagnosis of cancer, with significant family history of breast, ovarian, colon, or lung cancer or melanoma, or another strong history of cancer but no prior molecular diagnosis, heavy smokers or those exposed to carcinogens and mutagens. The individuals who meet criteria for inclusion will undergo cell-free DNA isolation and circulating-tumor DNA (ctDNA) analysis for the detection of genetic mutations associated with the possible development of a malignancy.

Cell-free DNA (cfDNA) is isolated from a blood plasma sample and tested for the presence of 96 specific well-described mutations in 9 cancer driver genes. The presence of more than 2 copies of a mutation may indicate the presence of a malignancy. Follow up with the subject's physician would be needed for an examination and any additional testing that the physician wants to perform to further assess for the development of cancer.

ctDNA Analysis for the Detection of Genetic Mutations

Glenn Braunstein, MD

Anja Kammesheidt, PhD

Pathway Genomics Corporation (Pathway Genomics), a San Diego, California company, is involved in the development and validation of new molecular diagnostic assays for the analysis of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) found in the plasma-derived DNA (cell-free DNA or cfDNA) in order to identify specific variants (mutations) in cancer driver genes. The purpose of testing for mutations in ctDNA is to detect and monitor cancer. All cells shed DNA into the bloodstream. Finding cancer-associated mutations in the cfDNA may lead to early detection of cancer in an otherwise apparently healthy (i.e. asymptomatic) individual or may allow the healthcare provider to more effectively monitor and treat a known cancer patient. The analysis is performed using a polymerase chain reaction (PCR)-based methodology where oligonucleotides are designed to target specific mutations in designated genes of interest followed by next generation deep sequencing of the amplified targets. Evaluation of the performance of these assays for screening for cancer in asymptomatic subjects is essential for the clinical validation of the use of these assays. The specific aim of this protocol is to obtain relevant human blood samples from individual subjects at higher than average risk for the development of cancer due to age, heredity, or environmental or toxic exposures for use in the statistical analysis of this method as an adjunct screening test for the potential presence of cancer.

The objectives of this study are to obtain human blood samples from asymptomatic subjects who have never been diagnosed with cancer, but who may be at increased risk for cancer due to heredity, exposures, age, or family history to assess the validity of screening healthy but at risk patients for cancer via analysis of ctDNA.

Specifically, the blood specimens will be collected from individuals who have responded to a self-administered health questionnaire that screens for higher risk of contracting cancer. Each participant will be asked to provide a 30 ml blood sample to be drawn by a primary care provider (PCP) or licensed phlebotomist. The specimens collected during the study may also be used in the research and development of new or modified molecular genetics assays. The results of these studies will be used to further the understanding of the use of ctDNA for the detection and monitoring of cancer in humans.

The blood samples are collected in blood collection tubes (BCT) called Cell-Free DNA BCT® manufactured by Streck and intended for collection, stabilization and transportation of cell-free plasma DNA. This device also stabilizes and preserves cellular genomic DNA present in nucleated blood cells and circulating epithelial cells (tumor cells) found in whole blood. This product has not been cleared by the U.S. Food and Drug Administration for In Vitro Diagnostic use and is labeled by Streck for research use only. Under the Clinical Laboratory Improvement Amendments (CLIA) regulations, laboratories are authorized to validate and use, as part of a laboratory-developed test (LDT), devices that have not been cleared or approved by the FDA. Pathway Genomics validated the CancerInterceptTM Detect molecular analysis system with the Streck tubes, in accordance with CLIA.

Once the specimen has been collected and sent to Pathway by the physician or the phlebotomist who collects the samples, all other processing and testing are conducted by Pathway laboratory personnel. The analysis begins with the separation of the plasma from the rest of the blood sample. cfDNA will then be isolated from each sample. The quantity of cfDNA is measured and then the sample is amplified via PCR for next generation sequencing. The results of the sequencing will then be analyzed for the presence of one or more of the 96 mutations analyzed in this assay. The data are then reviewed and a report will be generated.

Whole blood will be obtained, the plasma sample separated for the isolation of cell-free DNA, and the sample that may be stored will be excess plasma as well as potentially DNA from the buffy coat.

Utility of Plasma Circulating Tumor DNA (ctDNA) in Asymptomatic Subjects for the Detection of Neoplastic Disease

A cohort of 1000 or more individuals who are at high risk for the development of cancer will be tested for the presence of 96 well-described mutations in 9 cancer driver genes via ctDNA analysis. The number of individuals with one or more of the 96 assayed mutations will be assessed.

Among the cohort of subjects enrolled in the study in whom one or more of the 96 ctDNA mutations are detected, the number of copies per analyzed plasma sample will be calculated.

Within the samples found to contain one or more ctDNA mutation, the percentage of ctDNA within the total amount of cfDNA will be calculated.

The 1000 or more individuals in the study will be followed for 1 to 5 years to assess for the development of a malignancy. Special attention will be paid to the cohort who have initial assays indicating the presence of ctDNA. The subjects may be retested over time to show changing levels of ctDNA. Their own physicians will guide any follow up studies such as imaging or other laboratory testing. The test is designed as a means of case finding for cancer among individuals with high risk for development of cancer.

Pathway Genomics

Non colorectal cancer patients, verified by colonoscopy

Catherine Lofton-Day, PhD

Epigenomics is developing a colon cancer screening assay based on differential methylation of specific CpG sites for the detection of early stage disease. A genome-wide methylation analysis and oligonucleotide array study using DNA from various stages of colon cancer and normal tissue have been completed to obtain candidate CpG markers. Based on results obtained in the above studies, Epigenomics has moved to the final stages of feasibility with a specific, highly sensitive real-time marker assay that is able to detect colon cancer DNA in blood plasma.

From public health as well as health economics perspectives, the poor adoption of current screening options limits the effectiveness of CRC screening initiatives; as stated by Sidney Winawer, MD, "the best test is the one that gets done." Current CRC screening guidelines include FOBT, sigmoidoscopy (alone or with FOBT), or colonoscopy. Non-invasive screening is conducted using FOBT, which while inexpensive, exhibits a low compliance rate (around 16% in the US) due to its use restrictions, perceived inconvenience and lack of consumer acceptance. The gold standard procedure for CRC detection is colonoscopy; it exhibits excellent performance characteristics, but has a limited utility as a first line screen due to its high cost, healthcare delivery resource limitations, and inadequate patient acceptance. It is believed a noninvasive, first-line screening assay capable of detecting individuals with colorectal disease, confirmed by colonoscopy, would have greater utility for population screening.

Epigenomics has identified methylated gene regions that are specific for colorectal cancer or pre-malignant tissue. Aberrantly methylated genes represent attractive candidate markers for cancer screening, as cancer-specific methylation changes occur early in tumorigenesis, appear to be stable, yield a positive amplifiable signal, and can be assayed with high analytical sensitivity. Since methylation occurs early and in distinct genomic areas, it is possible to achieve high clinical sensitivity with a small number of methylated DNA markers. Studies have shown that aberrantly methylated DNA markers can be detected in tissue and body fluids and are highly correlated to colorectal cancer.

Residual plasma samples retained according to protocol.

Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay

Feasibility Study for Performance of Septin 9 in Plasma From Cases With Colorectal Cancer and Controls With Non-Diseased, Non-Colorectal Disease and Non-Colorectal Cancers

Michael Wandell VP Clinical, Regulatory, Quality

Plasma cell free DNA SEPT9 promoter methylation test for colorectal cancer screening.

Neil Mucci

Debora Goodman

Samir Gupta, MD

Karen Barger-Smith

Maureen Cooney

Alexandra Halalau, MD

Marie Macor

Greg Riedlinger, MD, PhD

Kim Leathers

Kathy Chmielewski

Ranee Chatterjee, MD

Kay Reiner, MPH, BSN, RN

Amy Howell-Harte, MD

Elyse Krupp

Dorian Williams, MD

This study will evaluate longitudinal performance of Epi proColon with respect to test positivity, longitudinal adherence to Epi proColon screening, adherence to follow-up colonoscopy and diagnostic yield, as well as assay failure rates.

Epi proColon is blood based screening test for colorectal cancer that is FDA - PMA approved. It is indicated for average risk patients who are unwilling or unable to be screened with other recommended screening tests, including colonoscopy or fecal occult blood tests.

The PERT study is designed to assess the test performance of Epi proColon when it is used annually for two consecutive years. Subjects enrolled in the study will be offered initial testing. Subjects with a positive result will be referred for colonoscopy. Subjects with a negative test result will be encouraged to be screened the following year. At the one year interval, test negative subjects will be reminded to be rescreened. Subjects with a positive test will be referred for colonoscopy, while subjects with a negative test will be be encouraged to participate in a screening program in subsequent years.

Longitudinal Performance of Epi proColon

Performance of Epi proColon in Repeated Testing in the Intended Use Population (PERT)

* Subjects will be tested with blood-based Epi proColon assay at initial enrollment, and tested again 1 year later (positive or negative test results)
* Subjects with positive test results with Epi proColon assay are referred to colonoscopy. Colonoscopy outcomes will be recorded (no evidence of disease or CRC)
* The difference in test specificity between initial and follow-up visits will be recorded.

Findings of colorectal cancer in subjects with a colonoscopy following a positive Epi proColon test will be recorded.

The adherence to repeated Epi proColon testing by patients who had a negative initial Epi proColon result will be recorded.

The rate of adherence to colonoscopy for patients with a positive Epi proColon result will be recorded

All procedure results will be recorded for patients who complete a colonoscopy evaluation following a positive Epi proColon test

The Epi proColon assay failure rate will be recorded during the duration of the study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Plasma-based Colorectal Cancer Screening Research & Development	NCT04027790	Colo-rectal Can...	Epi proColon	45 Years - 84 Years	Epigenomics, Inc
Non Invasive IDentification of Gliomas With IDH1 Mutation	NCT01703962	Non Invasive Di...		18 Years - 65 Years	Institut National de la Santé Et de la Recherche Médicale, France
Non Invasive IDentification of Gliomas With IDH1 Mutation	NCT01703962	Non Invasive Di...		18 Years - 65 Years	Institut National de la Santé Et de la Recherche Médicale, France
Observational Study to Compare Two Prostate Laser Enucleation Techniques in Terms of Urinary Incontinence	NCT05157724	Prostatic Hyper... Prostatic Adeno...	PLASMA	18 Years - 80 Years	Elsan
Presence of Circulating Tumor DNA in Colorectal Cancer	NCT01198743	Colorectal Neop...		18 Years - 85 Years	Assistance Publique - Hôpitaux de Paris
Microarray CGH Analysis of Circulating Tumoral Plasma DNA in NF1 Patients With MPNSTs	NCT01218152	Neurofibromatos...		-	KU Leuven
Utility of Plasma Circulating Tumor DNA (ctDNA) in Asymptomatic Subjects for the Detection of Neoplastic Disease	NCT02612350	Mutation Neoplasms	ctDNA Analysis ...	18 Years -	Pathway Genomics
Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay	NCT00696345	Colorectal Canc...		40 Years -	Epigenomics, Inc
Utility of Plasma Circulating Tumor DNA (ctDNA) in Asymptomatic Subjects for the Detection of Neoplastic Disease	NCT02612350	Mutation Neoplasms	ctDNA Analysis ...	18 Years -	Pathway Genomics
Longitudinal Performance of Epi proColon	NCT03218423	Colorectal Canc... Colorectal Neop...	Epi proColon	50 Years - 74 Years	Epigenomics, Inc
Cyclophosphamide, VELCADE, DOXIL, and Dexamethasone, (CVDD) in Newly Diagnosed Patients With Multiple Myeloma (MM)	NCT00750815	Multiple Myelom...	Cyclophosphamid... Bortezomib; Peg...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Presence of Circulating Tumor DNA in Colorectal Cancer	NCT01198743	Colorectal Neop...		18 Years - 85 Years	Assistance Publique - Hôpitaux de Paris
Evaluation of See.d as an Automated Blood Sample Preparator for Multiple Liquid Biopsy Applications	NCT06097156	Healthy Partici... Breast Cancer		18 Years -	Tethis S.p.A.
Plasma-based Colorectal Cancer Screening Research & Development	NCT04027790	Colo-rectal Can...	Epi proColon	45 Years - 84 Years	Epigenomics, Inc

Spots Global Cancer Trial Database for plasma

Every month we try and update this database with for plasma cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for plasma

Every month we try and update this database with for plasma cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for plasma cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.