Oxaliplatin ± Nivolumab in Combination With Trifluridine/Tipiracil or 5-fluorouracile in Frail Patients With Advanced, Recurrent or Metastatic Gastric, Oesophageal or Gastroesophageal Junction Cancer

NCT05476796 | Recruiting Phase 2 DMC

• 3 other identifiers: UC-GIG-22032022-000273-812024-512999-35-00
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 29

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.

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

Outcome Measures

Primary Outcomes (1)

• Progression free-survival

  The progression-free survival (PFS) is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

  From randomization to disease progression or death up to 5 years

Secondary Outcomes (5)

• Objective response rate

  5 years

• Overall survival

  From randomization to death from any cause, up to 5 years

• Incidence of Treatment Adverse Events

  Throughout study completion, up to 5 years

• Time to patient performance status deterioration >2

  From randomization to PS deterioration >2, up to 5 years

• Quality of life questionnaire - Core 30 (QLQ-C30)

  From baseline until disease progression, up to 1 year

Study Arms (2)

Trifluridine/Tipiracil + Oxaliplatin ± nivolumab

EXPERIMENTAL

Trifluridine/Tipiracil will be administered with a 14-day schedule (35 mg/m² twice-daily \[BID\] for 5 days followed by 9 days of recovery) until disease progression or intolerable toxicity. Oxaliplatin will be administered intravenously on day 1 of each treatment cycle (infusion duration: 2 hours), every 2 weeks. The first cycle will be administered at level -1 (70 mg/m²) and then increased to 85 mg/m² (if feasible) from the cycle 2 to 8 or until disease progression, whatever occurs first. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and Trifluridine/Tipiracil will be continued alone until disease progression or intolerable toxicity. ± nivolumab 240 mg (infusion duration 30 minutes, every 2 weeks) until disease progression or intolerable toxicity for a maximum of 2 years.

Drug: Trifluridine/Tipiracil; Drug: Oxaliplatin; Drug: Nivolumab

FOLFOX ± nivolumab

ACTIVE COMPARATOR

Folinic Acid 400 mg/m² (or 200 mg/m² if L-folinic acid) + oxaliplatin 85 mg/m² (infusion duration: 2 hours) followed by 5-FU bolus 400 mg/m² and then 5-FU 2400 mg/m² as a 46-hour continuous infusion. Treatment repeated every 14 days. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and 5-FU (simplified LV5FU2 regimen) or capecitabine (1000 mg/m² BID during 2 weeks every 3 weeks) will be continued alone until disease progression or intolerable toxicity. ± nivolumab 240 mg (infusion duration 30 minutes, every 2 weeks) until disease progression or intolerable toxicity for a maximum of 2 years.

Drug: FOLFOX regimen; Drug: Nivolumab

Interventions

Trifluridine/Tipiracil DRUG

Trifluridine/Tipiracil will be administered with a 14-day schedule (35 mg/m² BID for 5 days followed by 9 days of recovery) until disease progression or intolerable toxicity.

Also known as: Lonsurf

Trifluridine/Tipiracil + Oxaliplatin ± nivolumab

Oxaliplatin DRUG

Oxaliplatin will be administered intravenously on day 1 of each treatment cycle (infusion duration: 2 hours), every 2 weeks. The first cycle will be administered at level -1 (70 mg/m²) and then increased to 85 mg/m² (if feasible) from the cycle 2 to 8 or until disease progression, whatever occurs first. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and Trifluridine/Tipiracil will be continued alone until disease progression or intolerable toxicity.

Trifluridine/Tipiracil + Oxaliplatin ± nivolumab

FOLFOX regimen DRUG

Folinic Acid 400 mg/m² (or 200 mg/m² if L-folinic acid) + oxaliplatin 85 mg/m² (infusion duration: 2 hours) followed by 5-FU bolus 400 mg/m² and then 5-FU 2400 mg/m² as a 46-hour continuous infusion. Treatment repeated every 14 days. In case of limiting-oxaliplatin neuropathy and in all cases after 8 cycles, oxaliplatin will be stopped and 5-FU (simplified LV5FU2 regimen) or capecitabine (1000 mg/m² BID during 2 weeks every 3 weeks) will be continued alone until disease progression or intolerable toxicity.

FOLFOX ± nivolumab

Nivolumab DRUG

Nivolumab 240 mg (infusion duration 30 minutes, every 2 weeks) until disease progression or intolerable toxicity for a maximum of 2 years

Also known as: OPDIVO

FOLFOX ± nivolumab; Trifluridine/Tipiracil + Oxaliplatin ± nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed locally advanced, recurrent or metastatic non resectable adenocarcinoma of the stomach, oesophagus or gastroesophageal junction (GEJ) ineligible to curative treatment.
• No dysphagia or difficulty in swallowing.
• 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).
• At least one evaluable lesion according to RECIST v1.1 outside any previously irradiated area.
• No prior palliative chemotherapy.
• Age ≥18 years old.
• Patient eligible for FOLFOX chemotherapy
• 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
• No Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia \<16 ng/ml)

You may not qualify if:

• Patient with a performance status ECOG PS \>2.
• Other current or previous malignancy within the past 3 years (with the exception of squamous cell carcinoma of the skin treated by surgery).
• Adjuvant chemotherapy or radio-chemotherapy completed for less than 6 months.
• Peripheral neuropathy of NCI-CTCAE grade ≥2 at baseline.
• Patients with known allergy or severe hypersensitivity to any of the trial drugs or any of the trial drug excipients.
• 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.
• Previous treatment with trifluridine/tipiracil.
• Known Human Immunodeficiency Virus (HIV) infection.
• Interstitial lung disease.
• Prior pneumonitis requiring systemic corticosteroid therapy.
• Active infections.
• Pregnant or breastfeeding woman.
• Participation in another therapeutic trial within the 30 days prior to randomisation.
• Persons deprived of their liberty or under protective custody or guardianship.
• 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)

Sponsors & Collaborators

• UNICANCER: lead
• Servier: collaborator

Study Sites (29)

Clinique de l'Europe

Amiens, 80000, France

NOT YET RECRUITING

Hopital Privé Arras Les Bonnettes

Arras, 62000, France

RECRUITING

Institut Sainte Catherine

Avignon, 84000, France

RECRUITING

Centre Hospitalier de Beauvais

Beauvais, 60021, France

RECRUITING

CHU Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

RECRUITING

CHU Morvan

Brest, 29200, France

RECRUITING

Clinique Pasteur Lanroze

Brest, 29200, France

NOT YET RECRUITING

CH Cholet

Cholet, 49000, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

RECRUITING

CHU d'Estaing

Clermont-Ferrand, 63100, France

RECRUITING

Institut Andrée Dutreix - Clinique de Flandre

Coudekerque-Branche, 59210, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

WITHDRAWN

Hôpital Nord-Ouest Villefranche-sur-Saône

Gleizé, 69400, France

RECRUITING

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

Hôpital Saint Joseph

Marseille, 13008, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13009, France

RECRUITING

Hôpital Nord Franche Comté

Montbéliard, 25250, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Hôpital Saint Louis

Paris, 75010, France

RECRUITING

Hopital Europeen Georges Pompidou

Paris, 75015, France

RECRUITING

GH Diaconesses - Crois St Simon

Paris, 75020, France

RECRUITING

Institut Mutualiste Montsouris

Paris, 75674, France

RECRUITING

CHU de Poitiers

Poitiers, 86000, France

RECRUITING

CHU - Hôpital Robert Debré

Reims, 51092, France

RECRUITING

Institut Jean Godinot

Reims, 51100, France

RECRUITING

CHU Rouen - Charles Nicolle

Rouen, 76000, France

RECRUITING

ICO - Site René Gauducheau

Saint-Herblain, 44805, France

RECRUITING

Institut de cancérologie Strasbourg Europe

Strasbourg, 67033, France

RECRUITING

CHU Nancy - Hôpital Brabois

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

Related Publications (1)

• Botsen D, Chabaud S, Perrier H, Ammarguellat H, Jestin-Le-Tallec V, Olesinski J, Toullec C, Aparicio T, Ben Abdelghani M, Borg C, Bouche O, Coutzac C, Devaud H, Di Fiore F, Dubreuil O, Evesque L, Huguenin B, Muller M, Poureau PG, Oularue E, Tougeron D, Zaanan A, Ammari S, De Sousa Carvalho N, Decazes P, De La Fouchardiere C. Trifluridine/tipiracil + oxaliplatin +/- nivolumab vs FOLFOX +/- nivolumab in HER2 negative advanced oesogastric adenocarcinoma: The PRODIGE73-UCGI40-LOGICAN trial. Dig Liver Dis. 2024 Aug;56(8):1281-1287. doi: 10.1016/j.dld.2024.04.032. Epub 2024 May 17.

  PMID: 38762353 DERIVED

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Neoplasm Metastasis; Recurrence; Adenocarcinoma

Interventions

trifluridine tipiracil drug combination; Oxaliplatin; Folfox protocol; Nivolumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christelle DE LA FOUCHARDIERE

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicolas DE SOUSA CARVALHO

CONTACT

01 71 93 67 09; n-de-sousa@unicancer.fr

Laure MONARD

CONTACT

01 73 79 73 09; l-monard@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: July 27, 2022
• Study Start: June 23, 2023
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 24, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (29)