NCT07213557 Simvastatin Efficacy in ARID1A Mutated Advanced gastroESophageal Carcinoma Treated With Immunotherapy

Eligibility & Interventions

Eligibility Fast-Check

Enter your details for a quick preliminary check. This does not replace medical advice.

What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.

This trial targets 84 participants in total. It began in 2026-03-13 with a primary completion date of 2027-09.

Brief Summary

The investigators hypothesize that simvastatin (SIM) may improve the efficacy of first- line Nivolumab and Oxaliplatin-based chemotherapy, extending progression-free survival (PFS) as compared with Nivolumab and chemotherapy alone in patients with HER2 negative and ARID1A mutated advanced gastrooesophageal carcinoma (aGEC). Correlative mechanistic studies on tissue and blood samples, could help understanding the evolutionary dynamics of tumors in response to therapy thus optimizing the treatment approach and adding new insight into the antitumor mechanism of the combination approach.

Eligibility Criteria

Inclusion Criteria: 1. Written informed consent to study procedures and to correlative studies. 2. Aged ≥ 18. 3. Histologically proven of gastrooesophageal carcinoma 4. Diagnosis of advanced not operable or metastatic disease. 5. HER2 negative and ARID1A mutated status at initial diagnosis. 6. Available tumor tissue sample. 7. No prior treatments (chemotherapy, radiation or surgery) for aGEC. Surgery for primary GEC tumor before starting treatment is allowed. 8. Patient candidate to standard treatment with nivolumab and oxaliplatin-based chemotherapy as clinical practice (combined positive score ≥ 5). 9. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry. 10. Imaging-documented measurable disease, according to RECIST 1.1 criteria. 11. Estimated life expectancy of more than 12 weeks. 12. Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L and hemoglobin ≥ 9 g/dL. 13. Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 (in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN. 14. Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula). 15. Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. The same criteria, except for the status of ARID1A, will be followed to select the 28 consecutive HER2-negative and ARID1A non mutated aGEC patients of observational cohort. Exclusion Criteria: 1. Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 2. Prior chemotherapy or any other medical treatment for aGEC (previous adjuvant chemotherapy is allowed if terminated \> 12 months previously). 3. Any contraindication to Nivolumab, simvastatin or oxaliplatin-based chemotherapy. 4. Patients who have treatment with statins or fibrates or any medication for hypercholesterolemia. 5. Major surgical intervention within 4 weeks prior to enrollment. 6. Pregnancy and breast-feeding. 7. Any brain metastasis. 8. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study. 9. History of poor co-operation, non-compliance with medical treatment, unreliability or any condition that may impair the patient's understanding of the Informed consent form. 10. Participation in any interventional drug or medical device study within 30 days prior to treatment start. 11. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment. 12. Hypesensitivity to simvastatin. 13. Acute hepatitis or chronic hepatitis. 14. Personal or familial anamnesis of severe hepatopathy. 15. Known coagulation disorders. The same criteria will be followed to select the 28 consecutive HER2-negative and ARID1A non mutated aGEC patients of observational cohort.

Contact & Investigator

Frequently Asked Questions

Related Trials