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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Esophagus Adenocarcinoma
• Intervention / Treatment: Drug: Trifluridine/Tipiracil; Drug: Oxaliplatin; Drug: FOLFOX regimen; Drug: Nivolumab

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

• Study Type: Interventional
• Enrollment (Estimated): 118
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laure MONARD; Phone Number: 01 73 79 73 09; Email: l-monard@unicancer.fr
• Study Contact Backup: Name: Nicolas DE SOUSA CARVALHO; Phone Number: 01 71 93 67 09; Email: n-de-sousa@unicancer.fr

Study Locations

• France
  • Amiens, France, 80000
    • Not yet recruiting
    • Clinique de L'Europe
    • Principal Investigator: Fayçal HOCINE, Dr
  • Arras, France, 62000
    • Recruiting
    • Hôpital privé Arras les Bonnettes
    • Principal Investigator: Bruno HUGUENIN, Dr
  • Avignon, France, 84000
    • Recruiting
    • Institut Sainte Catherine
    • Principal Investigator: Clémence TOULLEC, Dr
  • Beauvais, France, 60021
    • Recruiting
    • Centre Hospitalier de Beauvais
    • Principal Investigator: Hanifa AMMARGUELLAT, Dr
  • Besançon, France, 25030
    • Recruiting
    • CHU Besançon - Hôpital Jean Minjoz
    • Principal Investigator: Christophe BORG, Pr
  • Brest, France, 29200
    • Not yet recruiting
    • Clinique Pasteur Lanroze
    • Principal Investigator: Veronique JESTIN-LE TALLER, Dr
  • Brest, France, 29200
    • Recruiting
    • CHU Morvan
    • Principal Investigator: Pierre-Guillaume POUREAU, Dr
  • Cholet, France, 49000
    • Recruiting
    • CH Cholet
    • Principal Investigator: You Heng LAM, Dr
  • Clermont-Ferrand, France, 63011
    • Recruiting
    • Centre Jean Perrin
    • Principal Investigator: Hervé DEVAUD, Dr
  • Clermont-Ferrand, France, 63100
    • Recruiting
    • CHU d'Estaing
    • Principal Investigator: Marine JARY, Dr
  • Coudekerque-Branche, France, 59210
    • Recruiting
    • Institut Andrée Dutreix - Clinique de Flandre
    • Principal Investigator: Jean-Philippe WAGNER, Dr
  • Dijon, France, 21079
    • Withdrawn
    • Centre Georges François Leclerc
  • Gleizé, France, 69400
    • Recruiting
    • Hôpital Nord-Ouest Villefranche-sur-Saône
    • Principal Investigator: Jonathan OLESINSKI, Dr
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
    • Principal Investigator: Clélia COUTZAC, Dr
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
    • Principal Investigator: Christelle DE LA FOUCHARDIERE, Dr
  • Marseille, France, 13008
    • Recruiting
    • Hôpital Saint Joseph
    • Principal Investigator: Hervé PERRIER, Dr
  • Montbéliard, France, 25250
    • Recruiting
    • Hôpital Nord Franche Comté
    • Principal Investigator: Christophe BORG, Pr
  • Nice, France, 06189
    • Recruiting
    • Centre Antoine Lacassagne
    • Principal Investigator: Ludovic EVESQUE, Dr
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint Louis
    • Principal Investigator: Thomas APARICIO, Pr
  • Paris, France, 75015
    • Recruiting
    • Hôpital Européen Georges Pompidou
    • Principal Investigator: Aziz ZAANAN, Pr
  • Paris, France, 75674
    • Recruiting
    • Institut Mutualiste Montsouris
    • Principal Investigator: Emilie SOULARUE, Dr
  • Paris, France, 75020
    • Recruiting
    • GH Diaconesses - Crois St Simon
    • Principal Investigator: Olivier DUBREUIL, Dr
  • Poitiers, France, 86000
    • Recruiting
    • CHU de Poitiers
    • Principal Investigator: David TOUGERON, Pr
  • Reims, France, 51100
    • Recruiting
    • Institut Jean Godinot
    • Principal Investigator: Damien BOTSEN, Dr
  • Reims, France, 51092
    • Recruiting
    • Chu - Hôpital Robert Debre
    • Principal Investigator: Olivier BOUCHE, Pr
  • Rouen, France, 76000
    • Recruiting
    • CHU Rouen - Charles Nicolle
    • Principal Investigator: Frédéric DI FIORE, Dr
  • Saint-Herblain, France, 44805
    • Recruiting
    • ICO - Site René Gauducheau
    • Principal Investigator: Judith RAIMBOURG, Dr
  • Strasbourg, France, 67033
    • Recruiting
    • Institut de cancérologie Strasbourg Europe
    • Principal Investigator: Meher BEN ABDELGHANI, Dr
  • Vandœuvre-lès-Nancy, France, 54500
    • Recruiting
    • CHU Nancy - Hôpital Brabois
    • Principal Investigator: Marie MULLER, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trifluridine/Tipiracil + Oxaliplatin ± nivolumab; 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; 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.; Other Names: Lonsurf; Drug: Oxaliplatin; 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.; Drug: Nivolumab; Nivolumab 240 mg (infusion duration 30 minutes, every 2 weeks) until disease progression or intolerable toxicity for a maximum of 2 years; Other Names: OPDIVO
Active Comparator: FOLFOX ± nivolumab; 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; 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.; Drug: Nivolumab; Nivolumab 240 mg (infusion duration 30 minutes, every 2 weeks) until disease progression or intolerable toxicity for a maximum of 2 years; Other Names: OPDIVO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Objective response rate (ORR) is defined as the percentage of patients with a best response during treatment being either Complete Response (CR) or Partial Response (PR).	5 years
Overall survival	The overall survival (OS) is the length of time from randomization that patients enrolled in the study are still alive.	From randomization to death from any cause, up to 5 years
Incidence of Treatment Adverse Events	The tolerance and safety will be evaluated by toxicity (acute [<1 months after the end of the trial treatment] and late [≥1 month after the end of the trial treatment), assessed using the Common terminology criteria for adverse events version 5.0 (CTCAE v5.0). CTCAE is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.	Throughout study completion, up to 5 years
Time to patient performance status deterioration >2	Time to performance status (PS) deterioration >2 is defined as the time between patient randomisation and the first date when PS>2. The Eastern Cooperative Oncology Group (ECOG) PS, a simple measure of functional status, determines ability of patient to tolerate therapies. It has scores ranging from 0 to 5 (0 = "fully active", 1 = "completely ambulatory", 2 = "<50% in bed during the day", 3 = ">50% in bed, but not bedbound", 4 = "bedbound", and 5 = "death").	From randomization to PS deterioration >2, up to 5 years
Quality of life questionnaire - Core 30 (QLQ-C30)	Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	From baseline until disease progression, up to 1 year

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Servier
• Investigators: Principal Investigator: Christelle DE LA FOUCHARDIERE, Institut Paoli-Calmettes

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 27, 2022

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Adenocarcinoma; Metastatic; FOLFOX; Gastrointestinal; Esophagus; Oxaliplatin; Recurrent; Gastric Adenocarcinoma; Locally advanced; Gastric; Gastroesophageal Junction Adenocarcinoma; Gastroesophageal Junction; Trifluridine/Tipiracil; Esophagus Adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Esophageal Neoplasms; Adenocarcinoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Antiviral Agents; Oxaliplatin; Nivolumab; Trifluridine
• Other Study ID Numbers: UC-GIG-2203; 2022-000273-81 (EudraCT Number); 2024-512999-35-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No