Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Observational

Joyson Poulose, MD

The purpose of this study is to find out more information about patients who have cancer (adenocarcinoma) of the esophagus or gastroesophageal junction (GEJ) who have been treated with chemotherapy and radiation but have not had surgery. The study will follow patients for 5 years to monitor for their cancer and to see how the standard medical care affects the daily life of patients.

Surveillance of Patients With Adenocarcinoma of the Gastroesophageal Junction or Esophagus

Study on Outcomes of Active Surveillance Among Invasive Locoregional Adenocarcinoma of Esophagus and Gastroesophageal Junction (GEJ) With Complete Response After Neoadjuvant Combined Chemoradiotherapy

The Guthrie Clinic

Digestive System Diseases

Rare Diseases

Barrett Esophagus

Esophageal Neoplasms

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Esophageal Cancer

Patients who weretreated by radical endoscopic resection for a high-risk mucosal EAC (HR-T1a N0M0)

Patients who were treated by radical endoscopic resection for a low-risk submucosal EAC (LR-T1b N0M0)

Patients who were treated by radical endoscopic resection for a high-risk submucosal EAC (HR-T1b N0M0)

diagnostic endoscopic resection

Man Wai Chan, MD

Wilda Rosmolen, MSc

M. Bourke, MD, PhD

R. Bisschops, MD, PhD

Emmanuel Coron

H. Messmann

Horst Neuhaus

Christoph Schlag

Oliver Pech

S. Seewald

R. Haidry, MD, PhD

R.E. Pouw, MD, PhD

The purpose of this study is to assess lymph node metastasis rate, distant metastasis rate, disease-specific mortality, and overall mortality in patients with Barrett's related T1b and high risk T1a esophageal adenocarcinoma (EAC) who underwent a diagnostic endoscopic resection.

The incidence of esophageal adenocarcinoma (EAC) has increased six-fold over the last three decades, making it the most rapidly rising cancer in the Western world. The main histologic risk factor for development of EAC is the presence of Barrett's esophagus (BE). BE can develop from non-dysplastic BE, to low (LGD) and high grade dysplasia (HGD) and, eventually, EAC.

The past two decades minimally invasive endoscopic resection (ER) has replaced surgical esophagectomy as first-choice therapy for the treatment of early neoplastic lesions in Barrett's esophagus. ER provides adequate tissue specimens, allowing for accurate histopathological staging of a lesion, by assessment of invasion depth, differentiation grade, presence of lympho-vascular invasion (LVI), and radicality of the resection. Endoscopic resection thus similarly fulfils a diagnostic and therapeutic role in the management of Barrett's neoplasia.

However, ER offers local treatment and does not include lymph node dissection as is still standard of care during esophagectomy. Therefore, the choice to perform endoscopic follow-up after a radical ER of an early EAC, or to refer a patient for additional surgery, is guided by the assumed risk of lymph node metastasis (LNM).

Data from previous studies show that the risk of LNM is only 1% in patients with low risk mucosal EAC after endoscopic treatment (i.e., infiltration depth limited to the mucosa, G1-G2, without LVI), and \<2% in low risk submucosal EAC (i.e., infiltration depth \<500μm, good to moderate differentiation grade (G1-G2), without LVI). In high risk submucosal EAC (i.e., infiltration depth ≥500 μm, and/or G3-G4, and/or LVI), the LNM risk is estimated to be much higher (16-44%). Nevertheless, these numbers are mainly based on old surgical series.

Current data is limited in terms of small and heterogeneous patient cohorts, and data for patients with high risk T1a EAC is not available at all. Therefore, we would like to conduct an international multicenter retrospective cohort study in \>10 centers to evaluate the safety and efficacy of endoscopic treatment and follow-up of patients with high risk mucosal and submucosal EAC. Our main focus will be the presence of lymph node metastasis and EAC related death.

Aim of this registration study is to collect data of the above-mentioned group of patients and thereby assess lymph node metastasis rate, disease-specific mortality, and overall mortality.

This study will be conducted according to the principles of the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act (WMO), the Medical Treatment Contracts Act (WGBO) and the Dutch Personal Data Protection Act (WBP). The investigators will perform the study in accordance with this protocol and will make sure that participants do not object to using their data. Collection, recording, and reporting of data will be accurate and will ensure the privacy, health, and welfare of research subjects during and after the study.

Outcomes of Endoscopically Resected High-risk Mucosal and Low- and High-risk Submucosal Adenocarcinoma Arising in Barrett's Esophagus

Outcomes of Endoscopically Resected High-risk Mucosal Adenocarcinoma and Low- and High-risk Submucosal Adenocarcinoma Arising in Barrett's Esophagus: an International Multicenter Retrospective Cohort Study

Confirmed by cytology and/or histology by performing FNA during EUS or biopsies

Primary tumor of distant metastasis should be histopathologically evalueted by taking biopsies.

Disease specific mortality is decribed as mortality directly linked to the esophageal adenocarcinoma (i.e., metastasized EAC, metastasized disease with a simultaneously primary cancer present and it cannot be ruled out (based on histology) that the metastases are related to the other primary cancer, death due to complications of the endoscopic procedure, death due to complications after surgery or CRT, no clear cause of death in patients who have metastases or untreated local recurrence). If patients are diagnosed with distant metastases, and subsequently die of a non-tumor related cause, patients will still be documented as tumor-related death. Will be measured in number of patients and percentages. Survival analysis using Kaplan Meier will be performed.

Overall mortality of study population (tumor-related + non-tumor-related deaths). Measured in numbers and percentages, survival analysis (KM).

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Professor of Gastrointestinal Endoscopy

Subjects with diagnosed locally advanced esophageal or gastroesophageal adenocarcinoma.

The ctDNA level will be measured using the Signatera platform developed by Natera, Inc. Signatera is a patient-specific, tumor informed custom-built ctDNA monitoring assay.

Circulating tumor DNA(ctDNA) level measurement

Medical College of Wisconsin Cancer Center Clinical Trials Office

Ben George, MD

Aditya Shreenivas, MD

This is an observational study to determine the feasibility of assessing tumor response utilizing ctDNA in patients of locally advanced esophageal and gastroesophageal junction (LA-EA/GEJ) cancer undergoing total neoadjuvant therapy (TNT) consisting of systemic chemotherapy (modified FOLFOX or FLOT/DFOX) followed by concurrent chemoradiation \[50.4 Gray (Gy) over approximately six weeks with concurrent radio sensitizing dose of carboplatin/paclitaxel\].

This study will explore the feasibility of assessing tumor response utilizing ctDNA in patients of Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma (LA-EA/GEJ) undergoing TNT consisting of systemic chemotherapy (modified FOLFOX or FLOT/DFOX) followed by concurrent chemoradiation (50.4 Gy over approximately six weeks with concurrent radio sensitizing dose of carboplatin/paclitaxel). The study schema in the following section illustrates the study design. In this observational study, patients with LA -EA/GEJ ca who are selected for the standard-of-care TNT will be enrolled. After obtaining informed consent, a venous blood sample and the archival tissue block from the initial diagnostic tumor biopsy will be sent to the Natera Inc. Patients that have an excellent response (defined by \>35% reduction in standardized uptake value (SUV) max on PET scan) from four cycles of standard-of-care induction chemotherapy (FOLFOX, DFOX or FLOT) will be treated with four additional cycles of therapy followed by chemoradiation and then assessed for curative intent surgery.

Patients who receive four cycles of neoadjuvant chemotherapy and don't have an excellent clinical response on the PET scan will not receive additional induction chemotherapy. They will be started on chemoradiation (50.4 Gy, radiation dose at radiation oncologists discretion with concurrent weekly carboplatin and paclitaxel) followed by assessment for surgery. Dose adjustment of radiation and chemotherapy will be allowed as per standard of care. Additional blood samples will be obtained for subsequent ctDNA measurements (after four cycles of neoadjuvant chemotherapy within +/- five days of the imaging study; after eight cycles for PET responders only; after the completion of chemoradiation around one to 14 days before surgery and 10 to 14 days after surgery). All patients may also choose to undergo additional serial ctDNA level measurements for surveillance after the surgery every three months for two years (optional).

Tumor response rate assessed by ctDNA will be compared with the response rate assessed by standard methods (PET scan, endoscopic ultrasound or CT/MRI) at different time points to explore if a significant correlation exists between these two response assessment methods. Imaging studies will also be discussed in the tumor board. If preliminary data support the hypothesis that peripheral blood ctDNA can be utilized for tumor response assessment in this scenario, a larger study will be conducted to validate this method. Once validated, ctDNA measurement can potentially supplement other expensive, uncomfortable, and time-consuming methods of tumor response assessment, such as endoscopic ultrasound and PET/CT.

This study does not involve any investigational therapeutic intervention. The only intervention planned in this study is obtaining multiple peripheral venous blood samples at prespecified time points described above for ctDNA level measurements.

Circulating Tumor DNA (ctDNA) in Locally Advanced Esophageal and Gastroesophageal (GE) Junction Adenocarcinoma

A Pilot Observational Study to Assess Feasibility of Tumor Response Assessment by Circulating Tumor DNA (ctDNA) in Patients With Locally Advanced Esophageal and GE Junction Adenocarcinoma Undergoing Treatment With Total Upfront Chemotherapy and Chemoradiation

This measure will quantify ctDNA concentration expressed in mean tumor molecules (MTM)/ml. Measurements will be made at Baseline, 8 weeks, 16 weeks, 14 days before surgery (approximately 8 months), 14 days after surgery, and every three months in follow-up up to 2 years. Results will be reported at Baseline, 14 days prior to surgery (approximately 8 months), 1 year, and 2 years.

This measure is the number of subjects with R0 (negative margin) surgical resection of tumor.

this measure is the number of subjects alive at 1 year and 2 years.

This measure is the number of subjects without evidence of recurrent tumor at at 1 year.

Medical College of Wisconsin

Professor

Oculocerebral Syndrome With Hypopigmentation

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Paclitaxel

Carboplatin

Docetaxel

Leucovorin

Fluorouracil

Albumin-Bound Paclitaxel

Oxaliplatin

Sequential Chemotherapy with Docetaxel, Oxaliplatin, and 5-Fluorouracil/Leucovorin followed by chemoradiation with concurrent carboplatin and paclitaxel

Chemotherapy with Docetaxel, Oxaliplatin, and 5-Fluorouracil/ Leucovorin

Sequential FLOT followed by chemoradiation

McKenna Russen

Amanda Emery

Lisa Deschaine

Lea Rodningen@uchelath.org

Lisa Lopez

Jeffrey Olsen

This study evaluates a novel regimen of induction chemotherapy using a combination of docetaxel, oxaliplatin, and leucovorin, with short term infusional 5-FU (FLOT), given prior to chemoradiotherapy with concurrent carboplatin and paclitaxel, as neoadjuvant therapy prior to definitive surgical resection for patients with adenocarcinoma of the esophagus or gastroesophageal junction

Clinical outcomes following standard of care therapy for resectable esophageal and gastroesophageal junction adenocarcinoma are suboptimal, with low rates of pathologic complete response (pCR) to current neoadjuvant treatment strategies. Although significant progress has been made by incorporation of neoadjuvant chemoradiation or perioperative chemotherapy, most patients will ultimately develop disease recurrence, with both locoregional and distant recurrence representing a significant component of failure. For patients receiving preoperative chemoradiation, a regimen consisting of concurrent carboplatin and paclitaxel with radiotherapy has been established as a standard of care based on the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS). In the long term results of CROSS, locoregional progression was noted in 22% of patients receiving neoadjuvant therapy, with distant progression in 39%.

Recent studies have also suggested perioperative chemotherapy as a potential alternative strategy for selected patients, based on results of the MAGIC trial, which included a subset patients with esophageal/GE junction tumor location, and demonstrated improved survival for patients receiving perioperative epirubicin, cisplatin, and infusional 5-fluorouracil (ECF) compared to surgery alone. The FLOT4-AIO trial has subsequently demonstrated a further overall survival benefit to a perioperative regimen of docetaxel, oxaliplatin, and leucovorin, with short term infusional 5-FU (FLOT) compared to ECF. A regimen of perioperative FLOT is currently being compared to preoperative chemoradiotherapy using the CROSS regimen in the ongoing ESOPEC trial (NCT02509286).

Given the significant risk of recurrence either with the CROSS preoperative chemoradiation regimen, or the perioperative FLOT regimen, it is plausible that selected patients may benefit from a combination of intensified systemic therapy using the FLOT backbone, in combination with sequential preoperative chemoradiation due to the known risk of locoregional recurrence in this population. This study evaluates the proposed neoadjuvant regimen of induction FLOT followed by neoadjuvant chemoradiation in patients with resectable cT3/T4 or node positive adenocarcinoma of the esophagus or gastroesophageal junction.

Induction FLOT With CROSS CRT for Esophageal Cancer

Phase II Study of Induction FLOT Followed by Neoadjuvant Chemoradiation in Patients With Resectable Adenocarcinoma of the Esophagus or Gastroesophageal Junction

The percentage of pathologic complete response at resection for patients who has completed the study regimen of induction FLOT, CROSS regimen chemoradiation, and surgical resection

The endpoint of overall survival will be defined by the proportion of evaluable patients that are living at a 1-year time interval from initial pathologic diagnosis. The endpoint of disease-free survival will be defined by the proportion of evaluable patients that are living and free of cancer recurrence at a 1-year time interval from initial pathologic diagnosis

The proportion of patients experiencing any ≥grade 3 and ≥grade 4 toxicity as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be recorded.

Patient reported quality of life outcomes using the validated European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)

Percentage reduction in SUVmax from the baseline to the post-chemotherapy PET.

The sensitivity and specificity of detectable ctDNA postoperatively to predict 1 year disease-free survival within the study cohort.

National Cancer Institute (NCI)

University of Colorado, Denver

Camurati-Engelmann Disease

Vactosertib

Protein Kinase Inhibitors

Enzyme Inhibitors

Vactosertib orally, 200 mg twice daily for five days a week for 2 weeks, followed by standard of care chemoradiotherapy, followed by Vactosertib for 4 weeks after standard of care chemoradiotherapy

200 mg orally, twice daily for five days a week, for 2 weeks and again for 4 weeks after chemoradiotherapy.

Neoadjuvant chemotherapy treatment as per standard of care.

Standard of Care Chemotherapy

Neoadjuvant radiation treatment as per standard of care.

Concurrent Radiation

Jennifer E Selfridge, MD, PhD

This interventional clinical trial aims to find ways of improving treatments for individuals with esophageal cancer. Laboratory-based studies show that using medicines that affect a protein called TGF-beta (TGFβ) can kill esophageal cancer cells in individuals who have localized esophageal adenocarcinoma and are being considered for standard-of-care chemoradiation prior to surgery. Participants of this study will take a pill called vactosertib for two weeks before starting standard of care chemoradiation. At the end of the two weeks of taking vactosertib, participants will have a Positron Emission Tomography Computer Assisted Tomography (PET CT) scan and undergo an endoscopy with a biopsy to determine if the vactosertib is working. After chemoradiation, participants will take vactosertib again for four weeks and then be considered for surgery.

Esophageal adenocarcinoma (EAC) is an aggressive malignancy with limited effective treatment options. In localized EAC (clinical stages II and III), the standard of care is pre-operative concurrent chemoradiation (CRT) followed by surgical resection, which results in pathologic complete response (pCR) in approximately 20% of participants, but with high rates of post-operative recurrence. It was recently discovered that EACs are driven by signaling through TGFβ Receptor I (TGFβRI), and in vivo models of EAC show tumor reduction by targeting this pathway with a novel small molecule inhibitor of TGFβRI called vactosertib. In this study, participants who have locally advanced EAC will be treated with vactosertib before and after standard of care chemoradiation to take advantage of natural windows of opportunity during which participants are being planned for their standard of care treatments.

This study is a phase 2, single-arm, Simon two-stage design. 15 participants will be enrolled in the first stage, with the potential of expanding to an additional 10 participants.

Oral TGF-beta Receptor I Inhibitor Vactosertib in SOC Chemoradiotherapy for Esophageal Adenocarcinoma

A Window of Opportunity Trial Evaluating the Oral TGF-beta Receptor I Inhibitor Vactosertib in Patients Undergoing Standard of Care Chemoradiotherapy for Locally Advanced Esophageal Adenocarcinoma

Determine if two-week treatment with single agent vactosertib induces metabolic response by PET CT imaging in primary EAC tumors. This will be measured as the rate of tumors that have decreased FDG tracer uptake by \>= 35% SUV on PET CT after 2 week treatment with vactosertib.

Evaluate the pathological response at the time of surgery after the combination therapy of CRT followed by vactosertib in patients with locally advanced EAC. This will be defined by the rate of pathological complete response at the time of surgical resection.

Correlate baseline expression of HNF4A with clinical response to vactosertib. HNF4A expression will be measured by immunohistochemistry and positive or negative expression will be correlated with rate of pathological complete response and metabolic response.

Determine if oral vactosertib is feasible in treatment of locally advanced EAC prior to and after CRT. Feasibility will be measured as the rate of patients able to complete \>= 75% of planned doses of vactosertib.

Jennifer Eva Selfridge

Principal Investigator

Esophageal Squamous Cell Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Squamous Cell

Pembrolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.

Peter C. Enzinger, MD

This research study is studying a targeted therapy as a possible treatment for advanced esophageal cancer.

The study intervention involved in this study is:

-Pembrolizumab

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Pembrolizumab for the participant specific disease but it has been approved for other uses.

Pembrolizumab, also known as KEYTRUDA or MK-3475, is approved in the USA and several other countries to treat other types of diseases.

The goal of this research study is to

-Evaluate the safety and efficacy of pembrolizumab in participants with advanced esophageal cancer that have not responded to standard treatment.

Pembrolizumab in Refractory Advanced Esophageal Cancer

A Phase II Study of Pembrolizumab in Refractory Advanced Esophageal Cancer

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Outcome defined as the number of patients experiencing at least one treatment-related grade 3-4 AE of any type during the time of observation.

Merck Sharp & Dohme LLC

Dana-Farber Cancer Institute

Peter C. Enzinger MD

Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Surveillance of Patients With Adenocarcinoma of the Gastroesophageal Junction or Esophagus	NCT02991547	Adenocarcinoma ...	Observational	18 Years - 80 Years	The Guthrie Clinic
Outcomes of Endoscopically Resected High-risk Mucosal and Low- and High-risk Submucosal Adenocarcinoma Arising in Barrett's Esophagus	NCT04818476	Barrett Esophag... Adenocarcinoma ... Submucosal Esop... High-risk Mucos...	diagnostic endo...	-	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Circulating Tumor DNA (ctDNA) in Locally Advanced Esophageal and Gastroesophageal (GE) Junction Adenocarcinoma	NCT05067842	Adenocarcinoma ...	Circulating tum...	18 Years - 80 Years	Medical College of Wisconsin
Induction FLOT With CROSS CRT for Esophageal Cancer	NCT04028167	Adenocarcinoma ... Adenocarcinoma ...	Sequential FLOT...	18 Years - 100 Years	University of Colorado, Denver
Oral TGF-beta Receptor I Inhibitor Vactosertib in SOC Chemoradiotherapy for Esophageal Adenocarcinoma	NCT06044311	Adenocarcinoma ... Locally Advance... Siewert Type I ... Siewert Type II...	Vactosertib Standard of Car... Concurrent Radi...	18 Years -	Case Comprehensive Cancer Center
Circulating Tumor DNA (ctDNA) in Locally Advanced Esophageal and Gastroesophageal (GE) Junction Adenocarcinoma	NCT05067842	Adenocarcinoma ...	Circulating tum...	18 Years - 80 Years	Medical College of Wisconsin
Induction FLOT With CROSS CRT for Esophageal Cancer	NCT04028167	Adenocarcinoma ... Adenocarcinoma ...	Sequential FLOT...	18 Years - 100 Years	University of Colorado, Denver
Induction FLOT With CROSS CRT for Esophageal Cancer	NCT04028167	Adenocarcinoma ... Adenocarcinoma ...	Sequential FLOT...	18 Years - 100 Years	University of Colorado, Denver
Pembrolizumab in Refractory Advanced Esophageal Cancer	NCT02971956	Esophageal Canc... Squamous Cell E... Adenocarcinoma ...	Pembrolizumab	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for adenocarcinoma esophagus