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Combination of Oxaliplatin and Nivolumab with Trifluridine/Tipiracil or 5-FU for Frail Patients with Advanced Gastric and Esophageal Cancer

Randomised Phase II Study Evaluating Trifluridine/Tipiracil Plus Oxaliplatin ± Nivolumab Versus FOLFOX ± Nivolumab in Patients With HER2 Negative Locally Advanced, Recurrent or Metastatic Gastric, Oesophageal or Oesogastric Junction Adenocarcinoma

Phase 2 Interventional Unicancer · NCT05476796

This study is testing a new combination of treatments for frail patients with advanced stomach or esophageal cancer to see if it helps them more than standard options.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment118 (estimated)
Ages18 Years and up
SexAll
SponsorUnicancer Academic / other
Drugs / interventionschemotherapy, prednisone, nivolumab
Locations29 sites (Amiens and 28 other locations)
Trial IDNCT05476796 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of combining oxaliplatin and nivolumab with either trifluridine/tipiracil or the FOLFOX regimen in frail patients suffering from advanced, recurrent, or metastatic gastric, esophageal, or gastroesophageal junction adenocarcinoma. The study is randomized and aims to compare these treatment combinations in patients who are ineligible for curative treatment. Participants must have histologically confirmed cancer and meet specific eligibility criteria, including adequate organ function and no prior palliative chemotherapy.

Who should consider this trial

Good fit: Ideal candidates for this study are frail patients aged 18 and older with advanced, recurrent, or metastatic gastric or esophageal adenocarcinoma who are ineligible for curative treatment.

Not a fit: Patients with HER2 overexpression or those who have previously received palliative chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for frail patients with advanced gastrointestinal cancers, potentially improving their outcomes.

How similar studies have performed: Other studies have shown promise with similar combinations of chemotherapy and immunotherapy in treating advanced gastrointestinal cancers, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Histologically confirmed locally advanced, recurrent or metastatic non resectable adenocarcinoma of the stomach, oesophagus or gastroesophageal junction (GEJ) ineligible to curative treatment.
2. No dysphagia or difficulty in swallowing.
3. No overexpression/amplification of HER2 (IHC 0 or 1+; if IHC is 2+, HIS must be negative). Known combined positive scor (CPS) PD-L1 score (result in % with the name of the method used). The microsatellite and mismatch repair (MMR) status of patient's tumour (MSI/MSS and pMMR/dMMR) must also be known at the time of screening (IHC and PCR tests have to be done).
4. At least one evaluable lesion according to RECIST v1.1 outside any previously irradiated area.
5. No prior palliative chemotherapy.
6. Age ≥18 years old.
7. Patient eligible for FOLFOX chemotherapy
8. Adequate organs function:

   * Absolute neutrophils count ≥1.5x10⁹/L
   * Platelets count ≥100x10⁹/L
   * Haemoglobin ≥9 g/L
   * Serum bilirubin levels \<2 times upper limit of normal (ULN), up to 2.5 times ULN in case of hepatic metastasis (biliary drainage allowed)
   * Transaminases \<5 times ULN
   * Creatinine clearance \>40 mL/min
9. No Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia \<16 ng/ml)
10. Women of childbearing potential must have a negative serum or urine pregnancy test done within 14 days before the first study treatment.
11. Patients must agree to use adequate contraception methods for the duration of study treatment and within 6 months after completing treatment.
12. Patients must be affiliated to a Social Security System (or equivalent).
13. Patient must have signed and dated a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
14. Availability of archived tumour material for ancillary studies

Exclusion Criteria:

1. Patient with a performance status ECOG PS \>2.
2. Other current or previous malignancy within the past 3 years (with the exception of squamous cell carcinoma of the skin treated by surgery).
3. Adjuvant chemotherapy or radio-chemotherapy completed for less than 6 months.
4. Peripheral neuropathy of NCI-CTCAE grade ≥2 at baseline.
5. Patients with known allergy or severe hypersensitivity to any of the trial drugs or any of the trial drug excipients.
6. Patients unwilling or unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.
7. Previous treatment with trifluridine/tipiracil.
8. Known Human Immunodeficiency Virus (HIV) infection.
9. Active Hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen \[HBsAg\] test prior to inclusion) or hepatitis C virus (HCV).
10. Interstitial lung disease.
11. Prior pneumonitis requiring systemic corticosteroid therapy.
12. Active infections.
13. Pregnant or breastfeeding woman.
14. Participation in another therapeutic trial within the 30 days prior to randomisation.
15. Persons deprived of their liberty or under protective custody or guardianship.
16. Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia (for men: QTc ≥450 msec, for women: QTc ≥470 msec)
17. Active systemic autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
18. Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease

Where this trial is running

Amiens and 28 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Gastric AdenocarcinomaEsophagus AdenocarcinomaGastroesophageal Junction AdenocarcinomaMetastaticRecurrentLocally advancedTrifluridine/TipiracilGastrointestinal
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.