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

NCT ID: NCT05476796

Last Updated: 2024-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

118 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-23

Study Completion Date

2027-01-31

Brief Summary

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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

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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

Conditions

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Gastric Adenocarcinoma Esophagus Adenocarcinoma Gastroesophageal Junction Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Trifluridine/Tipiracil

Intervention Type 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.

Oxaliplatin

Intervention Type 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.

Nivolumab

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

FOLFOX regimen

Intervention Type 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.

Nivolumab

Intervention Type DRUG

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

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Nivolumab

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

Intervention Type DRUG

Other Intervention Names

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Lonsurf OPDIVO

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Servier

INDUSTRY

Sponsor Role collaborator

UNICANCER

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christelle DE LA FOUCHARDIERE

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Locations

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Clinique de l'Europe

Amiens, , France

Site Status NOT_YET_RECRUITING

Hopital Privé Arras Les Bonnettes

Arras, , France

Site Status RECRUITING

Institut Sainte Catherine

Avignon, , France

Site Status RECRUITING

Centre Hospitalier de Beauvais

Beauvais, , France

Site Status RECRUITING

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

Site Status RECRUITING

CHU Morvan

Brest, , France

Site Status RECRUITING

Clinique Pasteur Lanroze

Brest, , France

Site Status NOT_YET_RECRUITING

CH Cholet

Cholet, , France

Site Status RECRUITING

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status RECRUITING

CHU d'Estaing

Clermont-Ferrand, , France

Site Status RECRUITING

Institut Andrée Dutreix - Clinique de Flandre

Coudekerque-Branche, , France

Site Status RECRUITING

Centre Georges François Leclerc

Dijon, , France

Site Status WITHDRAWN

Hôpital Nord-Ouest Villefranche-sur-Saône

Gleizé, , France

Site Status RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status RECRUITING

Hôpital Saint Joseph

Marseille, , France

Site Status RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status RECRUITING

Hôpital Nord Franche Comté

Montbéliard, , France

Site Status RECRUITING

Centre Antoine Lacassagne

Nice, , France

Site Status RECRUITING

Hôpital Saint Louis

Paris, , France

Site Status RECRUITING

Hopital Europeen Georges Pompidou

Paris, , France

Site Status RECRUITING

GH Diaconesses - Crois St Simon

Paris, , France

Site Status RECRUITING

Institut Mutualiste Montsouris

Paris, , France

Site Status RECRUITING

CHU de Poitiers

Poitiers, , France

Site Status RECRUITING

CHU - Hôpital Robert Debré

Reims, , France

Site Status RECRUITING

Institut Jean Godinot

Reims, , France

Site Status RECRUITING

CHU Rouen - Charles Nicolle

Rouen, , France

Site Status RECRUITING

ICO - Site René Gauducheau

Saint-Herblain, , France

Site Status RECRUITING

Institut de cancérologie Strasbourg Europe

Strasbourg, , France

Site Status RECRUITING

CHU Nancy - Hôpital Brabois

Vandœuvre-lès-Nancy, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Nicolas DE SOUSA CARVALHO

Role: CONTACT

01 71 93 67 09

Laure MONARD

Role: CONTACT

01 73 79 73 09

References

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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.

Reference Type DERIVED
PMID: 38762353 (View on PubMed)

Other Identifiers

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2022-000273-81

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-512999-35-00

Identifier Type: CTIS

Identifier Source: secondary_id

UC-GIG-2203

Identifier Type: -

Identifier Source: org_study_id

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