Clinical trial NCT05476796: Oxaliplatin ± Nivolumab in Combination With Trifluridine/Tipiracil or 5-fluorouracile in Frail Patients With Advanced, Recurrent or Metastatic Gastric, Oesophageal or Gastroesophageal Junction Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastric Adenocarcinoma
Esophagus Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Keywords: Metastatic
Recurrent
Locally advanced
Trifluridine/Tipiracil
Gastrointestinal
Adenocarcinoma
FOLFOX
Oxaliplatin
Gastric Adenocarcinoma
Esophagus Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Gastric
Esophagus
Gastroesophageal Junction
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Servier
First posted: 2022-07-27
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Oxaliplatin ± nivolumab in combination with trifluridine/tipiracil or 5-fluorouracile (5-FU) in frail patients with advanced, recurrent or metastatic gastric, oesophageal or gastroesophageal junction cancer.

Detailed description: 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

Eligibility 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

Primary outcomes:
measure: Progression free-survival
timeFrame: From randomization to disease progression or death up to 5 years
Secondary outcomes:
measure: Objective response rate
timeFrame: 5 years
measure: Overall survival
timeFrame: From randomization to death from any cause, up to 5 years
measure: Incidence of Treatment Adverse Events
timeFrame: Throughout study completion, up to 5 years
measure: Time to patient performance status deterioration >2
timeFrame: From randomization to PS deterioration >2, up to 5 years
measure: Quality of life questionnaire - Core 30 (QLQ-C30)
timeFrame: From baseline until disease progression, up to 1 year
Other outcomes:
Locations:
city: Amiens
country: France
facility: Clinique de l'Europe
city: Arras
country: France
facility: Hopital Privé Arras Les Bonnettes
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Beauvais
country: France
facility: Centre Hospitalier de Beauvais
city: Besançon
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Brest
country: France
facility: CHU Morvan
city: Brest
country: France
facility: Clinique Pasteur Lanroze
city: Cholet
country: France
facility: CH Cholet
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Clermont-Ferrand
country: France
facility: CHU d'Estaing
city: Coudekerque-Branche
country: France
facility: Institut Andrée Dutreix - Clinique de Flandre
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Gleizé
country: France
facility: Hôpital Nord-Ouest Villefranche-sur-Saône
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital Saint Joseph
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montbéliard
country: France
facility: Hôpital Nord Franche Comté
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: GH Diaconesses - Crois St Simon
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Poitiers
country: France
facility: CHU de Poitiers
city: Reims
country: France
facility: CHU - Hôpital Robert Debré
city: Reims
country: France
facility: Institut Jean Godinot
city: Rouen
country: France
facility: CHU Rouen - Charles Nicolle
city: Saint-Herblain
country: France
facility: ICO - Site René Gauducheau
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Nancy - Hôpital Brabois
Study officials:
affiliation: Institut Paoli-Calmettes
name: Christelle DE LA FOUCHARDIERE
role: PRINCIPAL_INVESTIGATOR
References: