Ongoing Clinical Trials for DNA Mismatch Repair Protein Gene Mutation
Currently, there are 2 ongoing clinical trials investigating treatments for cancers associated with DNA mismatch repair protein gene mutations. These trials are testing immunotherapy medications that help the immune system recognize and attack cancer cells with specific genetic characteristics.
Clinical trial locations
- France
- Germany
Study on Pembrolizumab for Patients with Localized Non-Metastatic MSI/dMMR Tumors or EBV+ Gastric Cancer
This trial is investigating the effectiveness of pembrolizumab in treating specific types of cancer that have not spread to other parts of the body. The study is taking place in France and is expected to continue until 2029.
Inclusion criteria: Participants must be at least 18 years old and have a confirmed localized tumor that has not spread. Eligible cancers include certain types of colorectal, rectal, gastric, gastro-oesophageal, oesophageal, endometrial, or small bowel cancers. The tumor must be classified as MSI/dMMR or EBV-positive gastric cancer, determined through special laboratory tests. Patients must have an ECOG Performance Status of 0 to 1, meaning they are either fully active or have mild symptoms but can still perform light activities. Adequate blood, liver, and kidney function is required, as confirmed by medical tests. Participants must have medical or health insurance coverage and be willing to attend scheduled visits and follow the treatment plan. Those of childbearing potential must agree to use effective birth control methods during and after the study.
Exclusion criteria: The study excludes patients whose tumors are not classified as MSI/dMMR or EBV-positive gastric cancer. Those who have already received cancer treatment, have cancer that has spread to other parts of the body, or are not within the specified age range cannot participate. The study also excludes individuals from vulnerable populations who may require special protection or care.
Trial focus: The main goal is to evaluate the rate of complete pathological response after surgery, meaning no viable tumor cells remain in the tumor or nearby lymph nodes. The study follows a structured timeline beginning with an initial assessment to confirm eligibility through specific tests. Treatment then begins with pembrolizumab administered as an intravenous infusion at a dosage of 25 mg/mL. Regular monitoring includes scheduled visits, laboratory tests, and imaging studies to assess treatment response and identify side effects. Surgery is performed to remove the tumor, followed by post-surgery evaluation to monitor recovery and potential cancer recurrence. Long-term follow-up continues throughout the study period to assess overall survival, progression-free survival, and quality of life.
Investigational drug: Pembrolizumab is an immune checkpoint inhibitor that helps the body’s immune system fight cancer. It works by blocking a specific protein called PD-1 on cancer cells, which allows the immune system to better recognize and attack these cells. The medication is delivered directly into the bloodstream through a vein.
Study on Atezolizumab for Patients with High-Risk Stage II or Stage III Colorectal Cancer Not Eligible for Oxaliplatin Chemotherapy
This trial is examining whether atezolizumab can improve disease-free survival rates in colorectal cancer patients who cannot receive standard oxaliplatin chemotherapy. The study is being conducted in Germany and is expected to conclude by February 2025.
Inclusion criteria: Participants must be 18 years or older and provide written informed consent. They must have a confirmed diagnosis of adenocarcinoma in the colon or rectum at high-risk stage II or stage III. The tumor must have been removed through successful surgery or be planned for removal. The cancer must be MSI-high or MMR-deficient, which are specific genetic characteristics. Patients must have an ECOG status of 0 to 2, indicating they can perform daily activities with varying levels of assistance. They must be unable to receive oxaliplatin-based chemotherapy or choose not to receive it. Adequate blood counts, liver enzymes, and kidney function are required. Those of childbearing potential must agree to use very effective birth control methods. Specific blood test results are required, with INR and PTT less than 1.5 times the normal limit within 7 days before joining.
Exclusion criteria: The study excludes patients who have a different type of cancer than the one being studied or have already received oxaliplatin-based chemotherapy. Those who have not had their tumor completely removed or do not plan removal, and those unwilling to follow study procedures cannot participate. Patients with other serious health conditions, active infections requiring treatment, or histories of certain heart, lung, liver, kidney, immune system, neurological, or psychiatric conditions are excluded. Pregnant or breastfeeding individuals, those participating in another clinical trial, or with known allergies to the study medication are not eligible. Patients with a history of substance abuse, those who have received live vaccines or had major surgery within certain time frames, or received certain medications before the study are also excluded.
Trial focus: The primary goal is to achieve improved disease-free survival rates at 3 years after treatment. The study includes a comparison with a placebo to evaluate atezolizumab’s effectiveness. Upon joining, patients provide informed consent and undergo health assessments to confirm eligibility. Treatment begins with atezolizumab administered intravenously, with dosage and frequency determined by the study protocol. The treatment continues for a specified period, with regular monitoring and assessments to evaluate patient response. Throughout the study, scheduled visits and examinations monitor health status, treatment effects, disease-free survival, overall survival, and quality of life. The study lasts up to 12 months of treatment, with follow-up continuing until the study’s conclusion.
Investigational drug: Atezolizumab is an immune checkpoint inhibitor that works by blocking a protein called PD-L1, which helps cancer cells evade the immune system. By blocking this protein, the medication helps the immune system recognize and attack cancer cells. It is administered as an infusion directly into the bloodstream and is being tested as an adjuvant treatment, meaning it is given after primary treatment to help prevent cancer recurrence.
Summary
Both ongoing trials focus on immunotherapy approaches for cancers with DNA mismatch repair deficiencies or microsatellite instability. The trials are geographically distributed between France and Germany, each investigating different immune checkpoint inhibitors: pembrolizumab and atezolizumab. The French trial takes a broader approach, including various tumor types beyond colorectal cancer, such as gastric, endometrial, and small bowel cancers, with a longer study duration extending to 2029. The German trial focuses specifically on colorectal cancer patients who cannot receive standard chemotherapy, with completion expected in 2025. Both studies share common themes of targeting MSI-high or MMR-deficient tumors and utilizing medications that enhance the immune system’s ability to recognize and attack cancer cells. These trials represent important research efforts to develop alternative treatment options for patients with specific genetic tumor characteristics who may not be suitable candidates for traditional chemotherapy approaches.
