Gastroesophageal Cancer Clinical Trials

What is Gastroesophageal Cancer?

Gastroesophageal cancer refers to a group of cancers that occur in the upper digestive tract, specifically gastric (stomach) cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma. These cancers are often grouped together due to overlapping risk factors, symptoms, and treatment approaches.

• Gastric cancer (Stomach cancer) originates in the lining of the stomach.
• Gastroesophageal junction cancer (GEJ) occurs where the esophagus meets the stomach.
• Esophageal cancer begins in the mucus-secreting cells of the lower esophagus and is the most common type of esophageal cancer in Western countries.

These cancers typically arise from chronic inflammation caused by factors such as Helicobacter pylori infection, gastroesophageal reflux disease (GERD), Barrett’s esophagus, smoking, alcohol consumption, and certain dietary habits.

Stages of Gastroesophageal Cancer:

• Stage I: Tumor confined to the innermost layers of the stomach or esophagus lining.
• Stage II: Deeper invasion into the wall and/or limited lymph node involvement.
• Stage III: Extensive local spread to lymph nodes and surrounding structures.
• Stage IV: Metastatic disease, spreading to organs such as the liver, lungs, or peritoneum.

Main signs and symptoms of Gastroesophageal Cancer:

• Difficulty swallowing (dysphagia)
• Unexplained weight loss
• Persistent indigestion or heartburn
• Chest or upper abdominal pain
• Nausea, vomiting, or early satiety
• Blood in vomit or stools (black, tarry stools)
• Loss of appetite or fatigue

It’s important to note that these symptoms can also be caused by non-cancerous conditions. However, if you experience any of these signs or other unexplained changes related to digestion or swallowing, it is essential to consult a healthcare provider promptly. Early detection and diagnosis of gastroesophageal cancer can lead to more effective treatment options and improved outcomes.

What does Treated and Untreated Gastroesophageal Cancer Mean?

Clinical trials are designed to meet patients wherever they are in their treatment journey. Whether you’re newly diagnosed or have already undergone therapy, there are trial options tailored to your situation:

• Treated Gastroesophageal Cancers refer to cases in which the patient has already received one or more forms of treatment. This may include surgery, chemotherapy, radiation, immunotherapy, or targeted therapy. For patients with disease progression after initial therapy, clinical trials can offer next-line treatment options that explore novel drug combinations, precision medicine approaches, or immunotherapy strategies.
• Untreated Gastroesophageal Cancers refer to cases in which the patient has not yet started systemic therapy. These patients may be eligible for first-line clinical trials evaluating promising investigational treatments before any standard treatment is administered.

Regardless of treatment history, there are clinical trials designed specifically for treatment-naïve, treatment-refractory, or relapsed/recurrent patients.

What Does Resectable (Surgery-Eligible) and Unresectable (Not Surgery-Eligible) Gastroesophageal Mean?

Surgical resectability is a key factor in determining the treatment approach for gastroesophageal cancers:

• Resectable Gastroesophageal cancer are those where the tumor can be surgically removed, either through gastrectomy (stomach removal) or esophagectomy (esophagus removal), often combined with lymph node dissection. These patients may also receive neoadjuvant (pre-surgical) or adjuvant (post-surgical) treatments like chemotherapy, radiation, or immunotherapy to improve outcomes.
• Unresectable Gastroesophageal cancer cannot be removed surgically due to extensive local invasion, distant metastasis, poor performance status, or other medical limitations. These patients typically receive systemic treatments such as chemotherapy, immunotherapy, or targeted therapy. Clinical trials for unresectable cancers are critical for testing innovative therapies, such as combination checkpoint inhibitors, antibody-drug conjugates, or tumor-targeted vaccines.

Patients with either resectable or unresectable disease can benefit significantly from clinical trial enrollment tailored to their specific condition and tumor biology.

What are the current treatment options for Gastroesophageal cancer?

Treatment for esophageal cancer, gastric cancer and GEJ cancer is multidisciplinary and based on tumor location, stage, molecular characteristics, and patient health:

• Surgery remains the mainstay of treatment for early-stage and selected locally advanced tumors. Common procedures include total or partial gastrectomy, transhiatal esophagectomy, etc. Surgery may be curative but is often used in combination with other modalities.
• Chemotherapy is frequently used as part of a multimodal approach, either before surgery (neoadjuvant) to shrink tumors or after (adjuvant) to eliminate microscopic disease.
• Radiation therapy, often combined with chemotherapy (chemoradiation), is used to control local tumor growth, especially in esophageal adenocarcinoma or in patients not fit for surgery.
• Targeted therapies are based on the molecular profile of the tumor. For example:
• HER2 targeted therapies
• VEGF-targeting agents
• Immunotherapy is a promising option for patients with PD-L1-positive, MSI-H/dMMR, or EBV-positive tumors. Immunotherapy are now part of the standard of care for selected patients in advanced stages.
• Supportive care plays a key role throughout treatment, helping manage side effects like dysphagia, nutritional deficiencies, and treatment-related fatigue.

Clinical trials explore all of these treatments and more, aiming to improve outcomes, reduce toxicity, and personalize therapy.

Next-Generation Sequencing (NGS) is transforming cancer treatment by revealing detailed insights into the molecular features of each tumor (Esophageal , GEJ and gastric cancer biomarkers). This powerful technology analyzes hundreds of genes at once, identifying mutations, amplifications, and biomarkers that may guide therapy decisions.

In gastroesophageal cancers, NGS may identify actionable alterations such as:

• ERBB2 gene mutations: It is a gene that encodes the HER2 (human epidermal growth factor receptor 2) protein, a receptor involved in cell growth and survival. ERBB2 (HER2) mutations play a significant role in a subset of gastric and gastroesophageal junction (GEJ) cancers.
• NTRK gene fusions: Though rare, these fusions are actionable with TRK inhibitors, which are approved for all solid tumors harboring NTRK fusions, including gastroesophageal cancers.
• RET gene fusions: These uncommon but significant alterations are targeted by RET inhibitors, often included in tumor-agnostic trials.
• BRAF V600E mutation: Though more common in other cancers, when found in gastroesophageal tumors, this mutation can open the door to BRAF-targeted therapies through precision oncology trials.

Clinical trials increasingly require NGS profiling as a prerequisite for enrollment, especially for trials testing targeted therapies or personalized combinations. Patients who undergo NGS testing can be matched more accurately with studies that align with their tumor’s unique characteristics, increasing the chances of clinical benefit.

Immunohistochemistry (IHC) is a critical diagnostic tool used to detect the presence of specific proteins in tumor tissues. The results of IHC testing not only guide immediate treatment decisions but also determine eligibility for numerous clinical trials.

• HER2 positive: Overexpression or amplification leads to HER2-targeted therapy eligibility. Clinical trials may explore new anti-HER2 agents or combinations with immunotherapy.
• MSI-H / dMMR status – Predicts strong benefit from immunotherapy with checkpoint inhibitors.
• PD-L1 expression – Helps determine candidacy for immunotherapy (evaluated in combination with IHC).
• CLDN18.2 positivity – A novel marker being investigated in trials for antibody-drug conjugates.

IHC testing is often the first step in identifying a patient’s eligibility for precision-based treatment. Many trials incorporate IHC findings into eligibility criteria or stratification groups, especially those evaluating checkpoint inhibitors, antibody-drug conjugates, and vaccine therapies.

Clinical trials play a crucial role in the advancement of Gastroesophageal Cancer treatment, offering patients access to new therapies and interventions before they are widely available. These trials are research studies. They test how safe and effective new treatments, medications, and therapies are. The goal is to see if these should be the standard care for treating Gastroesophageal cancer. Participation in a clinical trial can provide several benefits:

Benefits of Clinical Trials

• Access to New Treatments: Participants can access cutting-edge treatments that are not available outside the clinical trial setting.
• Contribution to Research: By participating in clinical trials, individuals contribute to medical research that could improve cancer treatment for future patients.
• Close Monitoring: Participants in clinical trials receive very close medical monitoring related to their treatment and overall health.

Types of Clinical Trials for Gastroesophageal Cancer

Clinical trials for Gastroesophageal Cancer can include:

• Prevention Trials: Aimed at finding better ways to prevent Gastroesophageal Cancer in people who have never had it or to prevent the cancer from returning.
• Screening Trials: Focus on finding new ways to detect Gastroesophageal Cancer early, when it may be more treatable.
• Treatment Trials: Test new treatments, new combinations of treatments, or new approaches to surgery or radiation therapy.
• Quality of Life Trials (Supportive Care): Explore ways to improve comfort and quality of life for Gastroesophageal Cancer patients.

Massive Bio offers a quick, easy, and free way to find clinical trials for patients like you. With our unique clinical trial matching system and compassionate team, Massive Bio can rapidly match you to clinical trials of new therapies. If you aren’t sure what form of Gastroesophageal cancer you have, that’s okay. Additional testing can help determine your exact diagnosis.

Cancer is an unfortunate reality that touches most of us at some point in our lives. If you or a loved one has cancer, you may have heard or read that clinical trials could offer access to innovative new options. But what exactly is a clinical trial? In this video, Massive Bio co-founder Arturo Loaiza-Bonilla, MD, explains how clinical trials work, what to expect if you enroll in one, and why a clinical trial can be an important option for many cancer patients.

We dream of the day when cancer disappears from our lives. Massive Bio is working tirelessly on achieving that goal.