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Study of Simvastatin with Nivolumab and Oxaliplatin for Patients with Advanced Stomach or Esophageal Cancer with ARID1A Mutation

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a type of cancer called advanced gastroesophageal carcinoma, which affects the stomach and esophagus. The study specifically looks at cases where the cancer is HER2 negative and has a genetic change known as ARID1A mutation. The trial aims to evaluate the effectiveness of a treatment combination that includes the drug Simvastatin, which is commonly used to lower cholesterol, alongside Nivolumab and Oxaliplatin-based chemotherapy. Nivolumab, also known by its code name BMS936558, is a medication that helps the immune system fight cancer, while Oxaliplatin is a chemotherapy drug that kills cancer cells.

The purpose of the study is to see how well this combination works in preventing the cancer from getting worse over a year. Participants will receive these treatments through an intravenous infusion, which means the medication is given directly into a vein. The study will also include other medications like Fluorouracil, known as 5-FU, and Calcium Levofolinate, which help enhance the effects of chemotherapy. Additionally, some participants may receive Simvastatin in tablet form to see if it improves treatment outcomes.

Throughout the study, participants will be monitored to assess how the cancer responds to the treatment and to check for any side effects. The study will last up to 60 weeks, during which the health and quality of life of the participants will be regularly evaluated. The goal is to determine if this treatment approach can help patients live longer without the cancer progressing. The trial will also compare results with a group of patients who do not have the ARID1A mutation to see if there are differences in treatment effectiveness.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Randomization and initial assessment
Upon joining the study, you will be randomly assigned to a treatment group. This process is called randomization and ensures that each participant has an equal chance of receiving any of the treatments being tested.
An initial assessment will be conducted to evaluate your current health status. This includes a review of your medical history, a physical examination, and any necessary imaging tests to document measurable disease according to specific criteria.
Step 2
Treatment initiation
You will begin treatment with a combination of medications. The main drugs used in this study are nivolumab and oxaliplatin-based chemotherapy. Nivolumab is administered as an intravenous infusion, which means it is given directly into your vein through a drip.
The chemotherapy regimen includes fluorouracil, oxaliplatin, and calcium levofolinate pentahydrate, all administered via intravenous infusion. Additionally, you will take simvastatin and capecitabine orally, which means you will swallow these medications in pill form.
Step 3
Ongoing treatment and monitoring
You will continue to receive the treatment until there is evidence of disease progression, unacceptable side effects, a decision by your doctor, pregnancy, or your choice to stop. Regular monitoring will be conducted to assess your response to the treatment and to manage any side effects.
Your health and the effectiveness of the treatment will be evaluated through regular check-ups, which may include physical exams, blood tests, and imaging studies. These assessments help determine if the treatment is working and if any adjustments are needed.
Step 4
Quality of life assessments
Throughout the study, your quality of life will be assessed using a questionnaire designed to understand how the treatment affects your daily life and well-being. This questionnaire will be completed at the start of the study and every 12 weeks thereafter.
These assessments are important to ensure that the treatment not only targets the disease but also considers your overall quality of life.
Step 5
End of study participation
Your participation in the study will conclude when the treatment is no longer effective, if you experience significant side effects, or if you choose to withdraw from the study.
At the end of your participation, a final assessment will be conducted to evaluate your health status and to discuss any further treatment options with your healthcare provider.

Who can join the trial?

19 criteria

Provide written informed consent to participate in the study and related research.
Have a disease that can be measured through imaging tests, as per RECIST 1.1 criteria (a standard way to measure how well a cancer treatment works).
Have an estimated life expectancy of more than 12 weeks.
check
Have adequate bone marrow function, which means:
- Absolute neutrophil count (ANC) of at least 1.5 x 10⁹/L (a type of white blood cell).
- Platelet count of at least 100 x 10⁹/L (cells that help with blood clotting).
- Hemoglobin level of at least 9 g/dL (a protein in red blood cells that carries oxygen).
- check
  Have adequate liver function, which means:
  - Total bilirubin level of 1.5 times the upper limit of normal or less (or 2 times if a biliary stent is present).
  - AST/ALT levels of 5 times the upper limit of normal or less (enzymes that indicate liver health).
  - Have adequate kidney function, which means:
    
    Serum creatinine level of 1.5 mg/dL or less (a waste product filtered by the kidneys).
    Creatinine clearance of at least 60 mL/min for males and 50 mL/min for females (a measure of kidney function).
    Have known dihydropyrimidine dehydrogenase (DPYD) activity (an enzyme important for breaking down certain drugs).
    Be aged 18 or older.
    Have a confirmed diagnosis of gastrooesophageal carcinoma (a type of cancer).
    Have advanced disease that cannot be operated on or has spread to other parts of the body.
    Have HER2 negative and ARID1A mutated status at the initial diagnosis (specific characteristics of the cancer).
    Have a sample of the tumor tissue available.
    Have not received prior treatments like chemotherapy, radiation, or surgery for advanced gastrooesophageal carcinoma. Surgery for the primary tumor before starting treatment is allowed.
    Be a candidate for standard treatment with nivolumab and oxaliplatin-based chemotherapy (a type of cancer treatment).
    Have an ECOG Performance Status of 1 or less at study entry (a scale to assess how a patient's disease is progressing).

Who cannot join the trial?

6 criteria

Patients with a different type of cancer than advanced or metastatic gastrooesophageal carcinoma that is HER2 negative and ARID1A mutated cannot participate. HER2 negative means the cancer does not have a protein called HER2 on its surface. ARID1A mutated means there is a specific change in the ARID1A gene.
Patients who are not candidates for the standard first-line treatment with nivolumab plus oxaliplatin-based chemotherapy cannot participate. Nivolumab is a type of medicine that helps the immune system fight cancer. Oxaliplatin-based chemotherapy is a treatment that uses drugs to kill cancer cells.
Patients who are pregnant or planning to become pregnant during the study cannot participate.
Patients who have experienced unacceptable side effects from similar treatments in the past cannot participate.
Patients who have a medical condition that the study doctor believes would make it unsafe for them to participate cannot join the study.
Patients who are unable to follow the study procedures or attend the required visits cannot participate.

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

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Azienda Ospedaliera Universitaria Federico II Di Napoli
Naples, Italy
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Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Naples, Italy
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IRCCS Istituto Nazionale Tumori Fondazione Pascale
Naples, Italy

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Investigated drugs

Simvastatin
is a medication that is commonly used to help lower cholesterol levels in the blood. In this clinical trial, it is being studied for its potential to help treat patients with a specific type of advanced stomach cancer that has a mutation in the ARID1A gene. Researchers are interested in seeing if Simvastatin can improve the effectiveness of the cancer treatment by slowing down the progression of the disease.
Nivolumab
is a type of cancer treatment known as an immunotherapy. It works by helping the body's immune system recognize and attack cancer cells more effectively. In this trial, Nivolumab is being used as part of the first-line treatment for patients with advanced gastroesophageal cancer. The goal is to see if it can help improve the outcomes for patients when used alongside other treatments.
Oxaliplatin-based chemotherapy
is a type of cancer treatment that uses a drug called Oxaliplatin, which is a chemotherapy medication. It works by damaging the DNA of cancer cells, which can stop them from growing and dividing. In this trial, Oxaliplatin-based chemotherapy is being used as part of the standard treatment for patients with advanced gastroesophageal cancer, in combination with other therapies, to see if it can help control the disease.

What is already known about the treatment

Simvastatin – Simvastatin is taken orally in the form of a tablet. It is currently being studied in clinical trials for its potential use in treating advanced or metastatic gastroesophageal cancer that is HER2 negative and has ARID1A mutations. The main therapeutic indication for Simvastatin in this context is to improve the effectiveness of standard first-line treatments, such as Nivolumab and Oxaliplatin-based chemotherapy. At the molecular level, Simvastatin works by inhibiting an enzyme involved in cholesterol production, which may also affect cancer cell growth. It is classified as a statin, a type of medication primarily used to lower cholesterol levels.

Investigated diseases

Advanced or metastatic gastroesophageal carcinoma – This is a type of cancer that occurs in the stomach and the esophagus, which is the tube connecting the throat to the stomach. In its advanced or metastatic stage, the cancer has spread beyond the original site to other parts of the body. The disease progresses as cancer cells grow uncontrollably, forming tumors that can invade nearby tissues and organs. Over time, these cancerous cells can enter the bloodstream or lymphatic system, spreading to distant organs such as the liver, lungs, or bones. As the disease advances, it can cause symptoms like difficulty swallowing, weight loss, and pain. The progression of the disease can vary, but it generally involves increasing tumor size and spread, leading to more severe symptoms.