Clinical Research Directory

Proton Beam Therapy in the Treatment of Esophageal Cancer

The investigators plan to include both operable and inoperable patients with esophagus cancer in this prospective trial. Since both proton and photon treatments are biologically equivalent, the investigators do not expect a difference in tumor control compared to intensity modulated radiation therapy (IMRT). The investigators have a prospective experience of physician-reported toxicity and patient outcome using IMRT for patients with inoperable esophagus cancer that will serve as a comparison group. For the resectable patients receiving trimodality therapy (chemoradiation followed by surgery), the investigators will carefully track toxicity and patient outcomes prospectively. The central hypothesis is that the biologic efficacy for tumor control should be similar between protons and photons, and therefore survival measures should be similar between the two groups, but that the main difference lies in the total severe toxicities experienced by the patients undergoing therapy.

Mayo Clinic Upper Digestive Disease Survey

The Mayo Clinic Conduit Report Card Questionnaires have been created in order to have a consistent evaluation tools for patients undergoing esophageal reconstruction or treatment or patients that are experiencing an upper digestive disease in order to standardize and validate outcome measures. Data will be used to establish the validation of the questionnaires/survey. Data will also lead to the establishment of "normal" or expected scores for patients undergoing each type of esophagectomy procedure and for upper digestive diseases. Data will contribute to creating treatment algorithms for symptom management for upper digestive diseases and for post-operative complications and symptoms as well as contribute to pre-operative education.

Multimodal Deep Learning for Predicting Treatment Response to Neoadjuvant Chemoimmunotherapy in Esophageal Cancer

This observational study aims to investigate a clinical cohort of patients with locally advanced esophageal cancer undergoing neoadjuvant chemoimmunotherapy. By integrating multimodal clinical data-including demographic characteristics, medical history, imaging studies, pathological findings, and laboratory tests-and employing deep learning algorithms, the study seeks to develop predictive models for the early and accurate assessment of treatment response prior to surgery. Specifically, this study focuses on addressing the following key scientific questions: 1. Can multimodal clinical data be used to construct an accurate model for predicting pathological complete response (pCR) following neoadjuvant therapy? 2. Can deep learning models enable early identification of patients with suboptimal response to neoadjuvant therapy, defined as stable disease (SD) or progressive disease (PD), before surgery?

CA-4948 in Combination With FOLFOX/PD-1 Inhibitor +/- Trastuzumab for Untreated Unresectable Gastric and Esophageal Cancer

This is a phase I trial of CA-4948 in combination with FOLFOX/PD-1 inhibitor with or without trastuzumab for unresectable gastric, GEJ, and esophageal cancer. During the Dose Escalation portion of the study, different dose levels of CA-4948 in combination with FOLFOX/nivolumab will be evaluated by BOIN algorithm. Dose Expansion will include Cohorts A and B. Expansion Cohort A will enroll up to 12 patients with HER2 negative gastric, GEJ, and esophageal cancer at the expansion dose of CA-4948 determined during Dose Escalation and will use the same treatment regimen of FOLFOX/nivolumab. Expansion Cohort B will investigate CA-4948 at the dose determined during Dose Escalation in combination with FOLFOX/pembrolizumab and trastuzumab in up to 12 patients with HER2 positive disease; however, the initial 6 patients will be considered safety lead-in to confirm the safety and tolerability of this combination; if determined to be safe, an additional 6 patients will be enrolled for a total of 12 in Cohort B.

Retrospective Review of Esophageal Cancer at MSKCC

Residual tumor at the proximal or distal margin after esophagectomy is a known prognostic factor for poor survival outcomes in patients with esophageal cancer; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, the investigators sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection.

Ivonescimab in Comb. With FOLFOX in Advanced HER2 Neg. GEA

This is a single arm, open-label, phase II trial investigating the combination of ivonescimab with standard FOLFOX chemotherapy in 1L therapy for HER2- GEA.

The MOMENTUM Study: The Multiple Outcome Evaluation of Radiation Therapy Using the MR-Linac Study

The Multi-OutcoMe EvaluatioN of radiation Therapy Using the Unity MR-Linac Study (MOMENTUM) is a multi-institutional, international registry facilitating evidenced based implementation of the Unity MR-Linac technology and further technical development of the MR-Linac system with the ultimate purpose to improve patients' survival, local, and regional tumor control and quality of life.

Clinical Study on Noninvasive Evaluation of Ivonescimab Antibody Distribution and Expression in Esophageal Cancer Patients by 89Zr-AK112 PET Imaging

As a humanized bispecific antibody targeting PD-1 and VEGF-A, everolizumab exhibits high specificity for binding PD-1 and VEGF-A in vivo. This critical property was systematically validated in a recent molecular imaging study based on positron emission tomography (PET). The study utilized radiolabeled everolizumab to construct an everolizumab PET probe, enabling non-invasive and dynamic monitoring of drug distribution and targeting behavior in living organisms. The results demonstrated that the PET probe exhibited excellent target tissue enrichment in the HCT-116 colorectal cancer xenograft model. In vivo PET imaging revealed a sustained increase in tumor uptake over time, peaking at 48 hours post-administration at 13.73 ± 0.95% ID/g, indicating strong tumor retention. Blocking experiments (pre-injection of excess everolizumab) significantly reduced tumor uptake to 5.20 ± 0.10% ID/g (P=0.00011), strongly supporting that its in vivo targeting is mediated by PD-1/VEGF-A-specific interactions rather than nonspecific accumulation. At 48 hours, the tumor-to-muscle signal-to-noise ratio (T/M ratio) reached 15.62, with an outstanding target-to-background ratio explaining the superior efficacy and safety of everolizumab. Furthermore, in vitro distribution studies confirmed that the retention levels of this antibody in non-target organs such as the liver and blood were significantly lower than those in tumor tissues, suggesting favorable pharmacokinetic properties that may reduce associated potential toxicity risks. Histopathological analysis (H\&E staining) demonstrated no signs of inflammation, necrosis, or other pathological damage in major organs (including the heart, liver, spleen, and kidneys), indicating that evolocimab exhibits good biocompatibility and tolerable safety characteristics.

Virtual Reality for GI Cancer Pain to Improve Patient Reported Outcomes

Patients with digestive tract malignancy often experience severe and unremitting abdominal pain that negatively affects physical, emotional, and social function, as well as health related quality of life (HRQOL). Therapeutic virtual reality (VR) has emerged as a promising and evidence-based treatment modality for cancer pain. Users of VR wear a pair of goggles with a close-proximity screen in front of the eyes that creates a sensation of being transported into lifelike, three-dimensional worlds. To date, VR has been limited to short-term clinical trials for cancer pain. Moreover, limited research exists on theory-based VR modalities beyond mere distraction, such as VR that employs acceptance and commitment therapy (ACT) with components of biofeedback and mindfulness. To bridge these gaps, this study seeks to: (1) assess the impact of immersive VR on patient-reported outcomes (PROs), including pain, activity metrics, and opioid use among patients with visceral pain from a digestive tract malignancy; (2) assess differences in PROs, activity metrics, and opioid use between skills-based VR therapy vs. distraction VR therapy; and (3) determine patient-level predictors of VR treatment response in visceral cancer pain. To address these aims, the study will measure PROs and opioid use in 360 patients randomized among 3 groups and follow them for 60 days after enrollment: (1) an enhanced VR group receiving skills-based VR; (2) a distraction-based VR group receiving patient-selected VR videos; and (3) a VR sham control group using a VR headset with 2-D content. The results will inform best practices for the implementation of VR for visceral cancer pain management and guide selection of patient-tailored experiences.

Chemoradiotherapy in Esophageal or Esophagogastric Junction Cancer

Definitive chemoradiotherapy is the standard of care in unresectable esophageal or esophagogastric cancer. A multidisciplinary approach, including chemotherapy and radiotherapy, is important for these patients. Morerover, molecular targeting agents does not show clear efficacy in EC up to now. Nowadays, the pace of development of cancer immunotherapies is accelerating. Clinical evidence of the efficacy of immune checkpoint inhibitors and adoptive immunotherapies herald the onset of a new era in cancer immunotherapy. There have also been recent developments to provide a promising frontier in extending the use of immunotherpay or targeting agents to radiotherapy. The purpose of this study was to explore the optimal treatment modalities including PD-1/PD-L1 antibody or targeted drug for patients with unresectable esophageal or esophagogastric junction cancer.

Imaging and Blood-Based Biomarkers for the Evaluation of Early Signs of Myocardial Injury After Thoracic Radiation Therapy

This study assesses for early signs of damage to the heart following chest radiation therapy using both imaging (cardiac magnetic resonance imaging and cardiac positron emission tomography) and changes in blood biomarkers. This study determines if any changes in the heart muscle can be detected either during the course of radiation therapy or shortly thereafter using specialized imaging techniques or blood tests. Cardiac magnetic resonance imaging may be used to help provide information about changes in the heart structure and function following radiation therapy. Positron emission tomography looks at differences in how the heart takes up radioactive sugar which is injected into the vein to assess changes in heart function following radiation therapy. This study may help identify patients at risk of heart issues following radiation therapy to the chest and ultimately help in the development of more effective and safe treatments for cancer in the future.

Target-specific immunoPET Imaging of Digestive System Carcinoma

The aim of this study is to establish and optimize the target-specific PET/CT imaging method, and its physiological and pathological distribution characteristics, on the basis of which the diagnostic efficacy of the above imaging agents in digestive system malignant tumors will be evaluated.

A Trial of the Combination of Afatinib and Palbociclib in Previously Treated Advanced Esophageal Squamous Cell Carcinoma

The goal of this clinical trial is to learn if Afatinib plus Palbociclib works in previously treated recurrent or metastatic esophageal squamous cell carcinoma. It will also learn about the safety of the combination of Afatinib and Palbociclib. The main questions it aims to answer are: What is the safe and tolerable dose of Afatinib when combined with 100 mg of Palbociclib (administered orally, three weeks on and one week off)? Does the combination therapy of Afatinib and Palbociclib induce a tumor response in patients with recurrent or metastatic esophageal squamous cell carcinoma who have received prior treatments?

Endoluminal Vacuum Therapy to Prevent Anastomotic Leakage After Esophagectomy Due to Esophageal Cancer

A prospective, multi-centre, exploratory and observational one-arm study to evaluate preventive Endoluminal Vacuum Therapy(pEVT) to prevent anastomotic leakage after esophagectomy due to esophageal cancer. The main objective is to evaluate the potential protective effect of prophylactic preemptive endoluminal vacuum therapy on esophageal-gastric anastomosis dehiscence after esophagectomy.

Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer

This is a single-arm clinical trial to evaluate the feasibility of a chemotherapy regimen using adaptive, individualized dose escalation of 5-FU chemotherapy for patients who have good tolerance of the initial dose. Study participants will also receive oxaliplatin chemotherapy together with 5-FU, at standard doses. The goal of the study is to examine the feasibility and effectiveness of this approach, using individualized dose escalation of 5-FU in patients who do not have serious side effects at lower doses.

Combination of Cadonilimab and Chemoradiotherapy in Esophageal Cancer (EC-CRT-006)

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer. However, as high as more than 40% of patients with esophageal cancer experienced locoregional recurrence after definitive CRT. Immune checkpoint inhibitors targeting PD-1/PD-L1 and/or CTLA-4 have shown substantial clinical benefits in advanced esophageal cancer. Recently, the combination of immunotherapy with CRT has emerged as a promising strategy to improve clinical outcomes in esophageal cancer. The aim of this study was to evaluate the efficacy and safety of cadonilimab (a bispecific PD-1/CTLA-4 antibody) combined with induction chemotherapy followed by definitive radiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Acupuncture for Oxaliplatin-induced Peripheral Neuropathy in Gastro-intestinal Cancer Patients

ACUPOX is a multicenter, open label, 2-cohort based phase II clinical study evaluating the interest of a standardized protocol of verum acupuncture in treatment of Oxaliplatin-induced peripheral neuropathy in patients with gastro-intestinal solid tumors who discontinued oxaliplatin-containing chemotherapy.

Tislelizumab Combined With Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma Followed by CRT or Surgery

To explore the non-inferiority of the 2y-OS rate of tislelizumab combined with chemotherapy after sequential CRT in the treatment of resectable esophageal squamous cell carcinoma compared with the surgical group

Radiation Dose Intensification With Accelerated Hypofractionated Intensity Modulated Radiation Therapy and Concurrent Carboplatin and Paclitaxel for Inoperable Esophageal Cancer

Rates of local disease control in patients with locally advanced esophageal cancer who are not candidates for surgical resection are suboptimal. Despite treatment with chemotherapy and radiation therapy approximately half of patients will develop recurrence of their cancer at the site of the original primary cancer. Salvage therapy options are largely ineffective and nearly all patients who develop local disease recurrence will succumb to their cancer. Recent clinical trials for lung cancer have demonstrated that local tumor control can be improved safely with accelerated hypofractionated radiation therapy regimens in order to achieve radiation dose intensification. This clinical trial aims to adapt those techniques and assess the safety of such a regimen for the treatment of inoperable thoracic esophageal cancers.

Tislelizumab Combined With Chemotherapy for the Perioperative Treatment of Esophageal Squamous Carcinoma

Evaluating the rate of pathologic complete remission in patients with squamous esophageal cancer treated perioperatively with tislelizumab in combination with chemotherapy

Proton Therapy for Esophageal Cancer

The goal of this phase II study is to investigate the feasibility, toxicity and efficacy of a regimen incorporating a proven systemic regimen, carboplatin /paclitaxel, with conformal proton modality, followed by definitive surgery. In most combined-modality trials to date, chemotherapy regimens have included cisplatin, usually in conjunction with 5-fluorouracil. In designing the regimen, the investigators attempt to improve on the standard cisplatin/5-fluorouracil regimen in several ways. First, full-dose paclitaxel is added to the regimen. This agent has activity against advanced esophageal cancer and is also a potent radiosensitizer. Second, the substitution of carboplatin for cisplatin has resulted in reduced toxicity of various combination regimens similar to that used by CROSS trial and allows for easier administration in the outpatient setting.4 Third, for localized esophageal cancer, dose distribution patterns achievable with proton beam could potentially offer important clinical advantages relative to those achievable with x-rays (photons).19 Based on this, the investigators believe that this study should be conducted with the radiation modality that offers the best dosimetry achievable at our institution.

Tislelizumab as Single-Agent Neoadjuvant Immunotherapy in Resectable Esophageal Squamous Cell Carcinoma

Tislelizumab in resectable esophageal squamous cell carcinoma

Chemoradiation Versus Esophagectomy for Locally Advanced Esophageal Cancer

The aim of this study is to compare outcomes in Chinese patients with locally advanced resectable esophageal squamous cell cancer who have received either surgery or definitive chemoradiation (CRT) by the randomized, open-label, multicenter trial.

Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors

This is a first-in-human, Phase 1/2 open-label, multicenter, dose-escalation, safety, pharmacokinetics (PK), and biomarker study of CBX-12 in subjects with advanced or metastatic refractory solid tumors.