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Simvastatin Efficacy in ARID1A Mutated Advanced gastroESophageal Carcinoma Treated With Immunotherapy

ConditionAdvanced or Metastatic Gastrooesophageal Carcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute, Naples

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

Written informed consent to study procedures and to correlative studies.

Aged ≥ 18.

Histologically proven of gastrooesophageal carcinoma

Diagnosis of advanced not operable or metastatic disease.

Disqualifiers

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.

Prior chemotherapy or any other medical treatment for aGEC (previous adjuvant chemotherapy is allowed if terminated > 12 months previously).

Any contraindication to Nivolumab, simvastatin or oxaliplatin-based chemotherapy.

Patients who have treatment with statins or fibrates or any medication for hypercholesterolemia.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

Treatment groups

84 Participants
are divided into 3 treatment groups
Group A: ARM A - standardActive comparator 1 intervention
Group B: ARM BExperimental treatment 1 intervention
Group C: ARM COther 1 intervention

Trial outcomes

Primary outcomes

1

Progression Free Survival rate at 1-year (PFS 1-year)

Progression Free Survival rate at 1-year (PFS 1-year) PFS 1-year is defined as the rate of assessable patients alive and not progressed after 1 year from initiation of study (i.e randomization) to the first documentation of: objective disease progression by RECIST 1.1 criteria, including deterioration of clinical conditions preventing radiological restaging, treatment interruption due to AEs followed by initiation of an alternative antineoplastic treatment, or death due to any cause, whichever occurs first in one year. It will be measured as the rate of assessable patients alive and without disease progression, as previously defined, at 1 year.

Time frame
up to 1 year to randomization

Secondary outcomes

1

Objective Tumor Response Rate (ORR)

Objective Tumor Response Rate (ORR) defined as the proportion of patients with complete/partial response, assessed according to RECIST criteria 1.1.

Time frame
up to 1 year last patients randomized
2

Disease Control Rate (DCR)

Disease Control Rate (DCR) defined as the proportion of patients with complete/partial response and stable disease as their best response, assessed according to RECIST criteria 1.1.

Time frame
up to 1 year to randomization
3

Progression-free survival (PFS)

Progression-free survival (PFS) measured as the time from the date of randomization until the date of the first observation of disease progression or death due to any cause, whichever occurs first, or the last date of follow up.

Time frame
up to 1 year to randomization
4

Overall survival (OS)

Overall survival (OS) calculated as the time from the date of randomization until the date of death from any cause, or the last date of follow up.

Time frame
up to 1 year to randomization

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute, Naples

Lead sponsor

Source ClinicalTrials.gov
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