Neoplasms

Digestive System Diseases

All Conditions

Behaviors and Mental Disorders

Rectal Neoplasms

Fecal Incontinence

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Quality of Life

Side-to-End Anastomosis as neorectal reconstruction technique in low anterior resection (LAR)

Transverse Coloplasty pouch as neorectal reconstruction technique in low anterior resection (LAR)

During the scheduled low anterior resection (LAR) in patients with distal rectal cancer and anticipated anastomosis in the mid or distal rectal third, the reconstruction phase of the LAR consists of the implementation of a side-to-end colorectal anastomosis.

Side-to-End Anastomosis

During the scheduled low anterior resection (LAR) in patients with distal rectal cancer and anticipated anastomosis in the mid or distal rectal third, the reconstruction phase of the LAR consists of the implementation of a transverse coloplasty pouch. For this purpose an end-to-end colorectal anastomosis is initially performed, followed by a longitudinal incision of approx. 8-10 cm length proximal of the anastomosis and a subsequent transverse suture in terms of the coloplasty technique.

Transverse Coloplasty

Markus Rentsch, MD

Sandro M Hasenhütl, MD

Andreas Hölscher, MD

Carolin Orlitsch, MD

Johann Spatz, MD

CSAR Trial's aim is to determine whether the transverse coloplasty pouch or the side-to-end anastomosis as rectal reservoir reconstruction offers the best functional results.

This study directly compares two neorectal reservoir-techniques, the transverse coloplasty and the side-to-end anastomosis, in low anterior resection in distal rectal cancer for the first time. Its focus is on the functional results. Besides stool frequency, the quality of life, safety of the procedures and the usage of stool modulating drugs is monitored in an 12 months-follow up regime.

Study participants will be randomized in two parallel study arms regarding their neorectal reconstruction in low anterior resection, the experimental arm using the side-to-end anastomosis and the control group using the transverse coloplasty technique.

Transverse Coloplasty vs. Side-to-end Anastomosis Following Low Anterior Resection (LAR): CSAR Trial

There is no plan to make individual participant data available to third parties beyond the study team.

Between group differences in stool frequency at t = 6 months postoperative

* Septic intraabdominal complications related to anastomosis (anastomotic insufficiencies, suture insufficiencies, abscesses);
* Wound infection

Quality of Life with focus on colorectally specialized questionnaires

Usage of antimotility drugs (e.g. loperamide) evaluated by standardized questionnaires

Ludwig-Maximilians - University of Munich

Principal Investigator

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Oral nutritional supplement: assignment according to consecutive random numbers.

Assignment according to consecutive random numbers.

3x1 dosage is given prior to surgery: 2x1 the day prior to surgery; 1x1 3-4h prior to initiation of anaesthesia;

PreOP Booster (food for special medical purposes)

Paul A.M. van Leeuwen, Prof.

The aim of this pilot study is to investigate effectiveness, tolerability and safety of an oral nutritional supplement (PreOP Booster), given to rectal tumour patients prior to low anterior resection.

Effectiveness and Tolerability of an Oral Nutritional Supplement (PreOP Booster) Given Before Surgery

Efficacy and Tolerability of a Preoperative Oral Nutritional Supplement (PreOP Booster) vs. Placebo in Surgical Patients (Pilot Study)

Fresenius Kabi

Dr. Steffen Benzing

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nervous System Diseases

Symptoms and General Pathology

Rare Diseases

Esophageal Neoplasms

Prostatic Neoplasms

Brain Neoplasms

Neoplasm Metastasis

Hypoxia

Neoplastic Processes

Signs and Symptoms, Respiratory

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Anti-Obesity Agents

Vasoconstrictor Agents

Respiratory System Agents

Imidazole

Phenylpropanolamine

Guaifenesin

Chlorpheniramine, phenylpropanolamine drug combination

Enzyme Inhibitors

Injection with the hypoxia tracer \[18F\]HX4 and PET imaging at baseline for esophageal, rectal, prostate cancer, primary brain tumor (grade IV glioma) and brain metastases and after 2 weeks of radiotherapy for esophageal, rectal and brain metastases

The \[18F\]HX4 PET scan will be performed, by administrating 444 MBq (12 mCi) \[18F\]HX4 via a bolus IV injection.

Injection with the hypoxia tracer [18F]HX4,

Philippe Lambin, Prof. dr.

Regulation of tissue oxygen homeostasis is critical for cell function, proliferation and survival. Evidence for this continues to accumulate along with our understanding of the complex oxygen-sensing pathways present within cells. Several pathophysiological disorders are associated with a loss in oxygen homeostasis, including heart disease, stroke, and cancer. The microenvironment of tumors in particular is very oxygen heterogeneous, with hypoxic areas which may explain our difficulty treating cancer effectively. Prostate carcinomas are known to be hypoxic. Increasing levels of hypoxia within prostatic tissue is related to increasing clinical stage, patient age and a more aggressive prostate cancer. Several researches indicated that hypoxia might also play a role in esophageal cancer. In glial brain tumors, hypoxia is correlated with more rapid tumor recurrence and the hypoxic burden in newly diagnosed glioblastomas is linked to the biological aggressiveness. In brain metastases CA-IX expression (a marker for hypoxia) is correlated to the primary non-small cell lung carcinomas. Hypoxia enhances proliferation, angiogenesis, metastasis, chemoresistance and radioresistance of hepatocellular carcinoma. The hypoxic markers HIF-1α, VEGF, CA-IX and GLUT-1 were all over expressed in colorectal cancer and its liver metastases. Based on literature, hypoxia in tumors originating or disseminated to prostate, esophagus, brain and rectum cancer will be studied in this trial.

Rationale: Non-invasive imaging of hypoxia with the aid of PET-scans could help to select the patients having a hypoxic tumor, who could be treated with specific anti-hypoxic treatments. The added value of additional anti-hypoxic treatments depends on the presence of hypoxia and adequate patient selection. Several 2-nitroimidazoles, labeled with Fluor-18 (18F) have already been used in patients to identify hypoxia. However, suboptimal image quality and unpredictable kinetics limit their use. In extensive pre-clinical models and clinical trials the combination of HX4 labeled with 18F showed to be a promising and non-toxic new probe to determine hypoxia. With this tracer the proportion of hypoxic tumors in several cancer types will be verified.

Objective: Determine if tumor hypoxia can be accurately visualized with \[18F\]HX4 in solid lesions.

Study design: Phase II, several solid tumors, single-centre, imaging, non-randomized, open label trial.

Study population:

Main patient characteristics are:

* Histological/cytological confirmed carcinoma of de esophagus, rectum or prostate or radiological suspicion for Grade IV glioma (primary brain tumor) or brain metastases.
* WHO performance status 0 to 2
* Adequate renal function (calculated creatinine clearance at least 60 ml/min).
* Capable of complying with study procedures

Main intervention: In addition to standard clinical care patients receive two additional PET scans after injection with the hypoxia tracer \[18F\]HX4.

Main study parameters/endpoints:

* Visualization and quantification of tumor hypoxia with \[18F\] HX4 PET imaging
* Exploring the potential relationship between \[18F\] HX4 uptake with local and locoregional tumor recurrence and survival
* Correlation of hypoxia imaging with blood hypoxia markers
* Correlation of hypoxia imaging with tumor tissue biomarkers
* Evaluation of tumor hypoxia changes during treatment.
* Spatial correlation of \[18F\] HX4-PET with imaging pre-treatment (if present from routine clinical practice)
* Spatial correlation of \[18F\] HX4-PET with imaging three months after treatment (if present from routine clinical practice)
* Quantitative and qualitative correlation of \[18F\] HX4-PET obtained before treatment and two weeks into treatment

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The radiation burden due to \[18F\]HX4 is similar to that encountered in many routine nuclear medicine procedures e.g. \[18F\]FDG PET. Administration of \[18F\]HX4 presents no known risks. In previous studies (healthy volunteers, phase I, phase II) no adverse effects were observed. There are no immediate potential benefits except the satisfaction to participate to improve of knowledge.

Tumor Hypoxia With HX4 PET in Several Diseases

Non-invasive Imaging of Tumor Hypoxia With [18F]HX4 Positron-Emission-Tomography (PET): A Phase II Trial

Visualization of tumor hypoxia with \[18F\] HX4 PET imaging

Quantification of tumor hypoxia with \[18F\] HX4 PET imaging

Exploring the potential relationship of \[18F\] HX4 uptake with local and locoregional tumor recurrence and survival

Correlation of hypoxia imaging with blood hypoxia markers

Correlation of hypoxia imaging with tumor tissue biomarkers

Evaluation of tumor hypoxia changes during treatment

Spatial correlation of \[18F\] HX4-PET with imaging pre-treatment (if present from routine clinical practice); performed by a rigid registration of the scans and a voxel wise comparison of the uptake within the tumor

Spatial correlation of \[18F\] HX4-PET with imaging three months after treatment (if present from routine clinical practice), performed by a rigid registration of the scans and a voxel wise comparison of the uptake within the tumor

Maastricht Radiation Oncology

This pilot study wishes to investigate feasibility and efficacy of the injected hydrogel spacers TraceIT® in sparing vagina/prostate in the treatment of rectal cancer patients.

TraceIT®

VMAT - fractionation Schedule : 1.8 Gy per fraction, one fraction per day, 5 fractions per week for the elective PTV and 2 Gy per fraction, one fraction per day, 5 fractions per week for the PTV-boost using a simultaneous integrated boost technique.

Volumetric Arc Therapy (VMAT)

Low anterior resection of the rectum: 8-10 weeks post-radiotherapy

Surgery

For advanced rectal tumors, the standard of care is neoadjuvant radiotherapy (RT) +/- chemotherapy followed by surgery 8-10 weeks later. Despite its proven efficacy in reducing local relapse, the neo-adjuvant treatment has been associated to non-negligible side effects, especially in terms of impaired sexual function. For females, pelvic RT is frequently associated to long-term complications such as vaginal stenosis (VS), vaginal dryness, and dyspareunia, while in men RT doses delivered to the neurovascular peri-prostatic bundles and penile bulb have been associated to the risk to develop erectile dysfunction.

In prostate cancer, hydrogel spacers have been evaluated to create space between the target (prostate) and the organ (rectum) to be spared during radiotherapy treatments. Clinical studies have shown the ease of spacer application; patient tolerance and, good clinical outcomes (decrease in rectal toxicities).

This pilot study wishes to investigate feasibility and efficacy of the injected hydrogel spacers TraceIT® in sparing vagina/prostate in the treatment of rectal cancer patients.

This is a feasibility prospective pilot study. Ten patients (5 males and 5 females) with a histologically proven locally advanced rectal cancer with the indication of neoadjuvant radiotherapy or radio-chemotherapy will be recruited for this study. Prior to enrollment, potential candidates will undergo a thorough physical and clinical examination and documentation on medical and surgical history. If eligible, a baseline planning computed tomography (CT) simulation will be performed at the Radiation Oncology Department before the TraceIT® implant. Participants will undergo a transperineal injection of TraceIT® spacer gel between rectum and vagina or prostate performed by a trained radiologist under transrectal ultrasound guidance. A CT simulation will be repeated within 3 to 5 days post injection using the same imaging modality and treatment position used the pre- TraceIT® injection. Radiation treatment plans will be generated using scans realized pre- and post- TraceIT® injection and compared using dose volume histograms (DVH) analyses. Tolerance, side effects, and adverse events related to the procedure will be recorded prospectively from the injection until week-4 after EBRT (External Beam Radiation Therapy) completion. Radiological status of the spacer will be evaluated on the preoperative magnetic resonance Imaging (MRI). Histopathological results and any serious and/or unanticipated adverse events following surgery procedure will be recorded retrospectively.

Organ-sparing With TraceIT® for Rectal Cancer Radiotherapy

TraceIT® Hydrogel Spacer Injections for Vagina and Erectile Bundles Sparing in Rectal Cancer Patients Treated With Neoadjuvant Radiotherapy: a Feasibility Study

Dosimetric parameters to determine effectiveness of this technique to reduce RT (radiotherapy) doses to the vagina/erectile bundles as assessed by comparative dosimetric studies.

University Hospital, Geneva

Thomas Zilli

MD, PD, Médecin adjoint agrégé

Gland and Hormone Related Diseases

Carcinoma

Pancreatic Neoplasms

Colonic Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Colonic Diseases

Pancreatic Cancer

Gastrointestinal Agents

Herbal and Botanical

Pancrelipase

Pancreatin

Cola

Participants with colorectal cancer ongoing surgery older than 18 years old.

Participants with pancreatic cancer ongoing surgery older than 18 years old.

Peter Bauer, Prof.

An international, multicenter study to identify tumor molecular particularities and neoepitopes among participants with colorectal and pancreatic tumors undergoing surgery.

Colorectal and pancreatic cancers are among the most common causes of cancer-related death over the world. Standard of care treatment for colon and pancreas cancer is stage dependent and includes surgical, chemotherapeutic, and radiation therapy. However, the current statistics underlines an urgent need for improved treatment. Patient-individualized treatments and enhancement of the immune response via vaccination are among new therapeutic options.

The enhancement of the immune response via vaccination is among new therapeutic options. Here, either cell-specific antigens, over-expressed tumor specific antigens or mutated tumor-specific antigens (neoepitopes) can be employed. Especially the latter possess the biggest potential for high specificity but presuppose an extensive characterization of the respective tumor. In order to identify a neoepitope-based vaccination approach for patient-individualized treatment options the molecular particularities of tumors have to be analysed.

The aim of this study is to identify tumor molecular particularities and neoepitopes among patients with colorectal and pancreatic tumors undergoing surgery.

Blood in EDTA tube, blood in Cell-free DNA tube (Streck tube), and blood in Heparin tube

Peptide-based Immunization for Colon- and and Pancreas-carcinoma

Peptide-based Immunization for Colon- and Pancreas-carcinoma (PICOP-GLOBAL): An International, Multicenter Protocol

Identification of tumor specific mutations on the genomic level using whole exome sequencing and/or whole genome sequencing

Direct comparison of tumor and non-tumor tissue to identify somatic mutations through RNA sequencing and proteomics analysis

Identification of neo-antigens epitopes at protein level via mass spectrography

CENTOGENE GmbH Rostock

Patients with histollogically confirmed locally advanced rectal adenocarcinoma (clinical T3-T4N0M0 or T(any) N+M0) treated with neoadjuvant CRT followed by curtive intent elective surgery.

Patients with histological diagnosis of locally advanced rectal adenocarcinoma \[clinical T3-T4N0M0 or T(any)N+M0\] were treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019.

Neoadjuvant chemoradiotherapy (CRT)

The combination of neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) is considered the standard treatment for locally advanced rectal cancer in the western world. Appropriate preoperative treatment and margin free surgery are key-elements in reducing the local-recurrence of the tumor and consequently improving overall survival.

Nevertheless, the local recurrence of stage II and III rectal cancer is still high, with current levels of 5% to 10% even when R0 resection is achieved. Most of the cases of loco-regional recurrence are associated with lateral lymph nodes (LLN) spread of cancer cells, which is not always controlled by the preoperative chemotherapy. As a matter of fact, the incidence of LLD metastases has been estimated to range from 11% to 22% in patients with T3/4 rectal cancer below the peritoneal reflection.

In order to improve these poor outcomes, Japanese surgeons have adopted extended lymphadenectomy with the dissection of lateral extramesorectal lymph nodes as the standard of care for T2-3 low rectal cancer patients5. While this approach is widely used in Japan and Korea, western surgeons have preferred a less aggressive approach, indicating lateral lymph node dissection (LLND) only in presence of clinically highly suspicious lateral pelvic lymph nodes on baseline magnetic resonance imaging (MRI). Thus, it is essential to identify preoperative predictive factors of LLN metastasis.

Even if MRI is considered the optimal diagnostic tool in rectal cancer, its accuracy for LLN staging is considered poor, especially after neoadjuvant treatment. LLNs often change in both features and size after CRT, and this behaviour might not be in concordance with the response of the primary tumor.

To the best of our knowledge, no consensus exists on whether the risk of local recurrence should be determined by assessing the features of LLN on the primary MRI or on the restaging MRI. Moreover, the relation between LLN response and primary tumor regression grade after neoadjuvant CRT needs to be thoroughly explored.

This multicenter cohort study aimed to investigate factors on primary and restaging MRI associated with lateral nodal recurrence and to identify patients who may benefit from LLND after neoadjuvant treatment for locally advanced rectal cancer.

The present is an international multicenter observational retrospective study. All consecutive patients admitted with a histologically confirmed locally advanced rectal adenocarcinoma \[clinical T3-T4N0M0 or T(any)N+M0\] treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019 at four academic high-volume institutions: the Division of Colon and Rectal Surgery, Mayo Clinic, Rochester (MN), USA; the Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; the Division of Minimally-Invasive Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, and the Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano - Milan.

All included patients had a pelvic MRI at baseline and a second pelvic MRI after neoadjuvant CRT. Interpretation and reporting of MRI for baseline staging was performed through a structured report adopted by each center involved in the present study. All MRI reports were presented according to international standards and validated by board-certified specialized lower gastrointestinal radiologists.

Oncological Impact of Lateral Nodes in Rectal Cancer

Lateral Lymph Node Features and Tumor Regression Grade After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: Impact on Oncological Outcomes.

Preoperative MRI feauteres assosiated with lateral nodal recurrence

Mayo Clinic

Niguarda Hospital

Patients with a diagnosis adenocarcinoma of the rectum will provide a tumor sample from their diagnostic biopsy and surgical procedure for research purposes, including RNA gene expression analysis. In addition to a standard MRI, patients will have an Intravoxel Incoherent Motion MRI (IVIM) and a Dynamic Contrast Enhanced MRI (DCE-MRI) for research purposes.

A tumor sample from the diagnostic biopsy and surgical procedure will be used for research.

Diagnostic Biopsy and Surgical Procedure

At the end of a standard MRI, we will perform IVIM, which is a diffusion-weighted imaging sequence that simultaneously characterizes the microscopic diffusivity of water and the macroscopic transport of water via bulk flow. IVIM may more accurately reflect the properties of the tumor microenvironment including vascular permeability, interstitial fluid pressure, and response to neoadjuvant therapy.

Intravoxel incoherent motion MRI (IVIM)

Following a standard MRI scan, Dynamic Contrast Enhanced MRI (DCE-MRI) will be done. DCE-MRI is an indicator-dilution experiment in which the delivery and transcapillary transfer of a contrast agent, typically one of a number of gadolinium-based contrast agents (GBCA), is used to assess a number of parameters characterizing tissue physiology. In locally advanced rectal cancer patients, use of DCE-MRI for determining pathologic response has produced equivocal results but more promising data has been published recently in the cervical cancer literature.

Dynamic Contrast Enhanced MRI (DCE-MRI)

RNA will be collected from biopsy and surgical tissue for gene expression analysis.

RNA gene expression analysis

Marka Crittenden, MD, PhD

This is an observational study of tumor samples and MRI imaging in patients with colorectal cancers. A tumor sample, MRI scans, and treatment outcome data will be used for research purposes to see if it is possible to predict patients' response to treatment.

The quality of the immune environment in colorectal cancer biopsy samples correlates with disease-free survival and overall survival more so than current staging conventions. This study will use a scoring system called 'immunoscore' to characterize the immune enviroment. Researchers hypothesize that the immunoscore will correlate with outcomes of colorectal patients treated with neoadjuvant chemoradiation.

Patients who enroll in the study will all undergo a biopsy as part of their standard of care evaluation. Biopsies samples will be obtained and sent to pathology for paraffin embedded blocks for diagnostic evaluation and for subsequent research. Patients will also have tissue stored in RNA later for subsequent microarray analysis.

Immunoscore in Rectal Cancer

A Study to Determine the Immunopheotype of Locally Advanced Rectal Adenocarcinoma and Its Correlation With the Efficacy of Neoadjuvant Chemoradiotherapy

This project is being done to contribute pathology samples and patient outcome data to a larger data set intended to validate an algorithm to predict patient outcome based on pathology data obtained at diagnosis. As part of this project, pre-existing samples will be used. There will be new slides made from the samples that will be stained to identify immune response. Pathology analysis and images of the slides will be provided (without patient identifiers) along with de-identified patient outcome data to a central coordinating center.

Quantitative immunohistochemical analysis will be performed on parameters of interest on both pre-treatment biopsy specimens as well as post-operative specimens. The pre-treatment sample will be used to establish the immunophenotype score. The primary analysis will evaluate the ability of immunophenotype score to correlate with pathologic response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Transverse Coloplasty vs. Side-to-end Anastomosis Following Low Anterior Resection (LAR): CSAR Trial	NCT03074461	Rectal Cancer Rectal Neoplasm... Rectal Tumors Fecal Incontine...	Side-to-End Ana... Transverse Colo...	18 Years -	Ludwig-Maximilians - University of Munich
Effectiveness and Tolerability of an Oral Nutritional Supplement (PreOP Booster) Given Before Surgery	NCT00730808	Rectal Tumors	PreOP Booster (...	18 Years - 75 Years	Fresenius Kabi
Tumor Hypoxia With HX4 PET in Several Diseases	NCT02584400	Prostatic Neopl... Esophageal Neop... Neoplasm Metast... Rectal Neoplasm... Brain Neoplasm,...	Injection with ...	18 Years -	Maastricht Radiation Oncology
Organ-sparing With TraceIT® for Rectal Cancer Radiotherapy	NCT03258541	Rectal Tumors Rectal Cancer Advanced Cancer	TraceIT® Volumetric Arc ... Surgery	18 Years - 85 Years	University Hospital, Geneva
Peptide-based Immunization for Colon- and and Pancreas-carcinoma	NCT03871790	Colon Neoplasm Colon Adenocarc... Colon Cancer Colo-rectal Can... Rectal Cancer Rectal Neoplasm... Rectal Adenocar... Rectal Tumors Pancreatic Canc... Pancreas Cancer Pancreatic Neop... Pancreatic Aden...		18 Years -	CENTOGENE GmbH Rostock
Transverse Coloplasty vs. Side-to-end Anastomosis Following Low Anterior Resection (LAR): CSAR Trial	NCT03074461	Rectal Cancer Rectal Neoplasm... Rectal Tumors Fecal Incontine...	Side-to-End Ana... Transverse Colo...	18 Years -	Ludwig-Maximilians - University of Munich
Oncological Impact of Lateral Nodes in Rectal Cancer	NCT05592873	Colorectal Aden...	Neoadjuvant che...	18 Years -	Niguarda Hospital
Immunoscore in Rectal Cancer	NCT02017509	Cancer of the R... Neoplasms, Rect... Rectal Cancer Rectal Tumors Rectal Adenocar...	Diagnostic Biop... Intravoxel inco... Dynamic Contras... RNA gene expres...	18 Years -	Providence Health & Services
Organ-sparing With TraceIT® for Rectal Cancer Radiotherapy	NCT03258541	Rectal Tumors Rectal Cancer Advanced Cancer	TraceIT® Volumetric Arc ... Surgery	18 Years - 85 Years	University Hospital, Geneva

Spots Global Cancer Trial Database for rectal tumors