Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

During a scheduled outpatient gastroscopy, the tumor margins will be endoscopically marked by BioXmark™. BioXmark™ will be implanted at the most proximal margin of the tumor and 5 cm proximally of the tumor border.

BioXmark™

Michael P Achiam, MD, DMSCi

This study aims to evaluate if BioXmark™, a surgical marker, may efficiently and safely be used to preoperatively mark the proximal and distal resection line 5 cm proximal and distal to the tumor margin of gastroesophageal-junction adenocarcinoma (GEJ AC).

Furthermore, to determine if placing the resection margin according to the resection margin defined by BioXmark™ is superior to the current standard of a proximal resection line estimation by the individual surgeon based on the intraoperative findings.

In Denmark, the national guidelines for GEJ AC surgery are an R0 resection with a minimum 5 cm proximal and distal resection margin, measured in vivo. During the operation, the primary surgeon sets the resection margin according to the guidelines, with 5 cm on either side.

The Danish national guidelines are clear, but the literature behind them is not, and the recommendations for resection margins vary worldwide. With the lack of a strong literature-backed guideline and a surgical approach that is heavily dependent on the individual surgeon's estimate, the risk of a microscopic positive resection margin (R1 resection) increases. Both problems, namely resectability at the definitive surgery and the incidence of microscopic positive resection margins after resection, may be improved by preoperatively marking the tumor margins in vivo. This could be achieved with an endoscopically placed surgical marker.

One such surgical marker is BioXmark™, a liquid injectable and adherent fiducial marker that has shown promising results for image-guided adaptive radiotherapy in lung, bladder, and esophageal cancer. BioXmark™ is implanted during endoscopy and has appropriate visibility with good positional stability on CT, CBCT, and MRI. Furthermore, no adverse reactions or events have been reported yet.

The study will be performed as a feasibility study of BioXmark™ at the Department of Surgery \& Transplantation, Centre of Cancer and Organ Diseases. The investigators plan to include 10 patients who are scheduled to undergo curatively intended surgery for GEJ AC. The patients will be drawn from the existing operating program.

Preoperative Marking of the Oral Resection Margin in Esophageal Cancer With a Surgical Fiducial Marker - First Experiences

BioXmark™ feasibility in terms of visibility with ultrasound during surgery CT-scans after neoadjuvant and visibility and positional stability during CT-scanning following neoadjuvant chemotherapy preoperatively.

This is part of a safety evaluation and will be registered by CTCAE into Adverse Events (AE) and Serious Adverse Events (SAE)

Nanovi

Rigshospitalet, Denmark

Research Scholar

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fibrinolytic Agents

All Drugs and Chemicals

Plasminogen

Resected esophageal cancer will be qualitatively and semi-quantitatively analyzed for uPAR expression

uPAR immunohistochemistry

Michael Achiam, MD., Ph.D

The aim of this study is to investigate urokinase Plasminogen Activator Receptor (uPAR) microexpression in gastroesophageal cancer (adenocarcinomas) both qualitatively and semi-quantitatively and to evaluate if it offers a possibility for future imagining purposes.

* Sections of the tumor tissue will be HE stained.
* Sections of the tumor tissue will be stained with an uPAR antibody for immunohistochemistry.
* Immunohistochemical staining against cytokeratin which colors cancer cells will be made to assist the observer in the evaluation of uPAR microexpression pattern.
* A semiqualitative scale corresponding to the level of uPAR expression will be made.
* Quantitative polymerase chain reaction will be used to validate the immunohistochemistry uPAR expression pattern.
* An electronic scoring system (digital pathology) will be trained to access the expression of uPAR in both tumor- and normal tissue.

The patients will be drawn from the existing clinical biobank. The biobank is located at the department of pathology, Rigshospitalet. From this clinical biobank, a new temporary research biobank will be made. Supplementary sections from formalin-fixed paraffin embedded (FFPE) blocks containing tumor tissue will be cut and Haematoxylin and eosin (HE) and immunohistochemical (IHC) staining will be performed.

Urokinase-type Plasminogen Activator Receptor and Gastroesophageal Cancer

Urokinase-type Plasminogen Activator Receptor and Gastroesophageal Adenocarcinomas

Our primary objective is to investigate uPAR microexpression in gastroesophageal adenocarcinomas both qualitatively and semi-quantitatively. This will be done by a pathology analysis of gastroesophageal cancer resections.

A pathology staining will determine the uPAR in the tumor compared with the healthy cells.

Baseline statistical analysis of patient groups and their expression of uPAR in their resected tumor tissues will be made.

Michael Patrick Achiam

Consultant, MD, DMSci, Ph.D., FEBS-OG, Ass. Professor

Stomach Neoplasms

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

Pharmaceutical Solutions

Nivolumab

Ramucirumab

Rucaparib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

* Rucaparib 600 milligrams twice daily
* Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks
* Nivolumab 480 milligrams intravenous every 4 weeks
* Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy
* One dose level decrease of Rucaparib will be planned if toxicity develops in the first 6 patients
* 1 cycle= 28 days

* Rucaparib 600 milligrams twice daily
* Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks
* Nivolumab 480 milligrams intravenous every 4 weeks
* Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy
* 1 cycle= 28 days

* Rucaparib 600 milligrams twice daily
* Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks
* Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy
* 1 cycle= 28 days

Anwaar Saeed, MD

The study population is advanced gastric, gastroesophageal, and esophageal adenocarcinoma participants who have failed upfront standard of care chemotherapy. The goal is to demonstrate that Rucaparib plus Ramucirumab with or without Nivolumab has a higher response rate than what has been reported for Ramucirumab in previously treated patients. Trial will be a phase 1/2 trial. The Phase 1 portion will determine the recommended Phase 2 treatment dose for the combination of Rucaparib plus Ramucirumab and Nivolumab and enroll approximately 6-9 participants. The Phase 2 portion of the study will involve 52 participants allocated between two treatment groups comparing Rucaparib plus Ramucirumab with or without Nivolumab. The participants will be selected based on the results of a screening HRD gene panel.

Phase 1 - Safety Lead In - Enroll 6-9 molecularly unselected participants to determine the safety of the triplet combination of Rucaparib plus Ramucirumab and Nivolumab. One level dose de-escalation of Rucaparib will be planned based on dose limiting toxicity (DLT) signal of the first 6 participants run in phase.

Phase 2 - Parallel - Enroll 52 participants (26 in each cohort), open label, two treatment cohorts design evaluating Rucaparib plus Ramucirumab with or without Nivolumab. 50 percent (%) of participants enrollment to each treatment cohort will represent molecularly unselected population and the remaining 50% will be selected based on integrated screening tumor Homologous Recombination Deficiency (HRD) gene panel. The primary objective is efficacy by measuring the Overall Response Rate (ORR).

Rucaparib Plus Ramucirumab With or Without Nivolumab in Advanced Gastric and Esophageal Adenocarcinoma

A Phase I/II Trial of Rucaparib in Combination With Ramucirumab With or Without Nivolumab in Previously Treated Patients With Advanced Gastric and Esophageal Adenocarcinoma (RiME)

Defined as the highest dose studied for which the observed incidence of dose limiting toxicities (DLT) is less than 33%. DLTs will be measured per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Defined as the proportion of participants with overall response to therapy. Overall response is defined as the best response recorded, (including Complete Response (CR) and Partial Response (PR)), from the start of the treatment until the end of treatment. ORR will be measured per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Defined as the proportion of participants with overall benefit to therapy. Overall benefit is defined as the best response recorded, (including complete Response (CR), Partial Response (PR), and Stable Disease (SD)), from the start of the treatment until the end of treatment. Determine overall benefit of therapy using modified RECIST version 1.1

Reported as the proportion of participants that achieve PFS. PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first. Measured per modified RECIST version 1.1

Defined as the time from the start of treatment until death due to any cause, reported as the mean of all participants' OS. Measured per the medical record.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Preoperative Marking of the Oral Resection Margin in Esophageal Cancer With a Surgical Fiducial Marker - First Experiences	NCT05069766	Esophagus Cance...	BioXmark™	18 Years -	Rigshospitalet, Denmark
Urokinase-type Plasminogen Activator Receptor and Gastroesophageal Cancer	NCT04669951	Esophagus Cance...	uPAR immunohist...	18 Years -	Rigshospitalet, Denmark
Rucaparib Plus Ramucirumab With or Without Nivolumab in Advanced Gastric and Esophageal Adenocarcinoma	NCT03995017	Esophagus Cance... Stomach Cancer,...	Rucaparib Ramucirumab Nivolumab	18 Years -	University of Kansas Medical Center
Preoperative Marking of the Oral Resection Margin in Esophageal Cancer With a Surgical Fiducial Marker - First Experiences	NCT05069766	Esophagus Cance...	BioXmark™	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for esophagus cancer, adenocarcinoma