Esophageal and gastroesophageal junction cancers are serious diseases with limited cure rates, even when patients receive chemotherapy and surgery. New ways to improve treatment are urgently needed.
This study will test whether adding a commonly used cholesterol-lowering medication, simvastatin, to standard cancer treatment can improve outcomes. Simvastatin is widely used, safe, and inexpensive. Research suggests that it may also slow cancer growth by blocking pathways that cancer cells rely on for survival.
In this trial, patients will receive standard chemotherapy (with or without immunotherapy) before surgery. Half of the patients will also take simvastatin daily for up to two years. Researchers will compare how well tumors respond to treatment and whether patients remain cancer-free longer.
If successful, this approach could offer a simple and accessible way to improve survival for patients with these cancers without adding significant side effects or cost.
Signed, informed consent.
Age, 18 years or older.
Histological diagnosis of adenocarcinoma or poorly differentiated carcinoma of the esophagus or EGJ.
The tumour must be deemed potentially resectable by the surgical team. This assessment is based on complete staging imaging studies (detailed below) - clinical staging of the tumor and ruling out metastatic disease.
Prior esophageal or gastric malignancy.
History of allergic reactions to simvastatin or atorvastatin or similar chemical or biological compounds.
Ongoing cholesterol-lowering therapy (statins, fibrates, ezetimibe, PCSK9 inhibitors), in which case the patient is offered enrollment in the observational arm.
Hepatic dysfunction (alanine aminotransferase level more than three times the upper limit of the normal range) or renal dysfunction (creatinine level more than three times the upper limit of the normal range).
Parallel
FLOT (Fluorouracil+Leucovorin+Oxaliplatin+Docetaxel)
DrugStandard of care neoadjuvant FLOT
Simvastatin
DrugInvestigational drug added to standard of care FLOT or FLOT+D
Durvalumab
DrugStandard of care Durvalumab added to FLOT regimen.
MPR
Major Pathological Response
Statin-enhanced toxicity of standard-of-care regimen, specifically grade 3 or 4 adverse events
Statin-enhanced toxicity of standard-of-care regimen, specifically grade 3 or 4 adverse events, as per Common Terminology Criteria for Adverse Events (CTCAE) version 6.0, warranting dosage modification or stoppage of interventional drug or chemotherapy. CTCAE grading is from 1 to 5, while grade 1 is the least severe (mild) and grade 5 is the most severe (death).
2-year EFS
2-year event-free-survival (EFS), defined as elapsed time from date of randomization to date of recurrence (local or distant) or death, occurring after resection
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This trial is not recruiting at the moment. You can still explore other options:
