Adding simvastatin to nivolumab and oxaliplatin-based chemotherapy for ARID1A‑mutated advanced gastroesophageal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized, open-label phase 2 study enrolling patients with HER2-negative, ARID1A-mutated advanced or metastatic gastroesophageal carcinoma who are candidates for first-line nivolumab plus oxaliplatin-based chemotherapy (CPS ≥ 5). Participants are randomized 1:1 to receive standard nivolumab with XELOX or mFOLFOX6 chemotherapy with or without oral simvastatin 40 mg daily. Treatment continues until disease progression, unacceptable toxicity, or other discontinuation criteria, with maintenance fluoropyrimidine after 24 weeks for those without progression. Correlative tissue and blood studies are planned to track tumor evolutionary dynamics and explore mechanisms of response to the combination approach.

Why it matters

Who can join: the full rules

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.

Where it's running

• Istituto Nazionale Tumori Fondazione G. Pascale
  Naples, Italia, Italy Recruiting

Study contacts

• Study coordinator: Antonio Avallone, MD
• Email: a.avallone@istitutotumori.na.it
• Phone: 08117770357

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Intratumoral fluorescent nivolumab before surgery in head and neck cancer

  This study tests injecting fluorescently labeled nivolumab directly into head and neck tumors to see if it is safe and whether it reaches nearby lymph nodes before surgical removal.

  Recruiting Early Phase 1 Vanderbilt-Ingram Cancer Center · Nashville, Tennessee · NCT07741565

• Bexmarilimab plus nivolumab in solid tumors, melanoma, and NSCLC

  This trial tests whether adding bexmarilimab to nivolumab can help people with melanoma, non-small cell lung cancer, or other advanced solid tumors whose cancer stopped responding to immune therapy.

  Recruiting at 2 sites Phase 1/2 Institute of Cancer Research, United Kingdom · Manchester and 1 other locations · NCT07718243

• Cadonilimab with chemotherapy vs chemotherapy with/without nivolumab as first-line treatment for HER2-negative advanced gastric/GEJ cancer

  This study tests whether adding cadonilimab to chemotherapy helps people with newly diagnosed, unresectable or metastatic HER2-negative gastric/GEJ cancer live longer, compared with standard chemo alone (with or without nivolumab).

  Recruiting Phase 3 Akeso · Phoenix, Arizona and 24 other locations · NCT07700979

• Dendritic Cell Vaccine with HER2-targeted Therapy or Nivolumab for Breast Cancer with Leptomeningeal Metastasis

  This trial tests a dendritic cell vaccine added to trastuzumab for Her2-positive disease or to nivolumab for Her2-negative disease to see if it can be given safely to people with breast cancer that has spread to the leptomeninges.

  Recruiting Phase 2 H. Lee Moffitt Cancer Center and Research Institute · Tampa, Florida · NCT07694986

• First-Line Nivolumab plus Ipilimumab in unresectable hepatocellular carcinoma

  This study tests whether the combination of nivolumab and ipilimumab is safe and effective for adults with unresectable liver cancer in real-world care in Japan.

  Recruiting at 2 sites Bristol-Myers Squibb · Minato-ku, Tokyo and 1 other locations · NCT07679061

• Neuro-navigation-guided focused ultrasound with nivolumab for relapsed or progressive high-grade brain tumors in children

  This study tests whether using focused ultrasound to open the blood-brain barrier and give nivolumab is safe and feasible for kids with relapsed or progressive DMG/DIPG or other high-grade brain tumors.

  Recruiting Phase 1 Children's National Research Institute · Washington D.C., District of Columbia · NCT07664176

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.