Simvastatin Efficacy in ARID1A Mutated Advanced gastroESophageal Carcinoma Treated With Immunotherapy

Conditions

• Advanced or Metastatic Gastrooesophageal Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• standard nivolumab and oxaliplatin- based chemotherapy — DRUG
  Nivolumab will be administered as 30 minutes intravenous infusion at the dosage of 360 mg every 3 weeks or 240 mg every 2 weeks as flat dose followed by investigator's choice of oxaliplatin-based chemotherapy regimen: * XELOX (oxaliplatin 130 mg/m2 on day 1 and capecitabine 1,000 mg/m2 orally twice daily on days 1- 14 administered every 3 weeks) or * mFOLFOX6 (oxaliplatin 85 mg/m2 on day 1 followed by lederfolin 200 mg m2 on day 1, fluorouracil 400 mg m2 on day 1 and 2,400 mg m2 continuous infusion over 46 hours every 2 weeks)
• simvastatin in combination with standard nivolumab and oxaliplatin-based chemotherapy — DRUG
  Nivolumab will be administered as 30 minutes intravenous infusion at the dosage of 360 mg every 3 weeks or 240 mg every 2 weeks as flat dose followed by investigator's choice of oxaliplatin-based chemotherapy regimen: * XELOX (oxaliplatin 130 mg/m2 on day 1 and capecitabine 1,000 mg/m2 orally twice daily on days 1- 14 administered every 3 weeks) or * mFOLFOX6 (oxaliplatin 85 mg/m2 on day 1 followed by lederfolin 200 mg m2 on day 1, fluorouracil 400 mg m2 on day 1 and 2,400 mg m2 continuous infusion over 46 hours every 2 weeks) * SIM will be administered per os daily at a fixed dosage of 40 mg that represents the recommended dose as cholesterol lowering agents.

Study Details

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.

Key Dates

Start date

Mar 13, 2026

Status verified

Apr 2026

Primary completion

Sep 30, 2027

Completion

May 31, 2028

Study Design

Enrollment

84 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: ARM A - standard
  Patients with HER2 negative aGEC eligible for the standard treatment with nivolumab and oxaliplatin- based chemotherapy (CPS ≥ 5) will be evaluated for ARID1A expression by immunohistochemistry on tumor tissue. Patients with ARID1A mutated will be randomized to receive standard nivolumab and oxaliplatin- based chemotherapy (standard arm, ARM A) or simvastatin in combination with standard nivolumab and oxaliplatin-based chemotherapy (experimental arm, ARM B)
• Experimental: ARM B
  Patients with HER2 negative aGEC eligible for the standard treatment with nivolumab and oxaliplatin- based chemotherapy (CPS ≥ 5) will be evaluated for ARID1A expression by immunohistochemistry on tumor tissue. Patients with ARID1A mutated will be randomized to receive standard nivolumab and oxaliplatin- based chemotherapy (standard arm, ARM A) or simvastatin in combination with standard nivolumab and oxaliplatin-based chemotherapy (experimental arm, ARM B)
• Other: ARM C
  Observational Cohort: patients with ARID1A not mutated of observational cohort (ARM C) will be treated with standard treatment with nivolumab and oxaliplatin-based chemotherapy and compared with standard ARM A as exploratory comparison to evaluate the predictive value for immunotherapy of ARID1A.

Primary Outcome Measure

Progression Free Survival rate at 1-year (PFS 1-year) [ Time Frame: up to 1 year to randomization ]

Central Contacts

• Antonio Avallone, MD
  08117770357
  [email protected]