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

Gastric Adenocarcinoma Clinical Trial

— LOGICAN  

Official title:

Randomised Phase II Study Evaluating Trifluridine/Tipiracil Plus Oxaliplatin ± Nivolumab Versus FOLFOX ± Nivolumab in Patients With Gastric, Oesophagus or Gastroesophageal Junction Adenocarcinoma Locally Advanced, Recurrent or Metastatic, Ineligible for Triplet Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05476796
• Other study ID #: UC-GIG-2203
• Secondary ID: 2022-000273-81
• Status: Recruiting
• Phase: Phase 2
• Start date: June 23, 2023
• Est. completion date: January 2027

Study information

• Verified date: October 2023
• Source: UNICANCER
• Contact: Nicolas DE SOUSA CARVALHO
• Phone: 01 71 93 67 09
• Email: n-de-sousa[@]unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Randomized phase II study evaluating trifluridine/tipiracil plus oxaliplatin ± nivolumab versus FOLFOX ± nivolumab in patients with gastric, oesophagus or gastroesophageal junction adenocarcinoma locally advanced, recurrent or metastatic, ineligible for triplet chemotherapy

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 118
• Est. completion date: January 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 unfit for triplet chemotherapy = ECOG-PS=2 or Age =70 year old PLUS one frailty criteria on Activities of Daily Living (ADL)/Instrumental Activities of Daily Living (IADL) score or denutrition (defined by albumin <30 g/L).

8. Adequate organs function:

• Absolute neutrophils count =1.5x10?/L

• Platelets count =100x10?/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

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Neoplasms
• Esophagus Adenocarcinoma
• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

Intervention

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

Locations

Country	Name	City	State
France	Clinique de l'Europe	Amiens
France	Hopital Privé Arras Les Bonnettes	Arras
France	Institut Sainte Catherine	Avignon
France	Centre Hospitalier de Beauvais	Beauvais
France	CHU Besançon - Hôpital Jean Minjoz	Besançon
France	CHU Morvan	Brest
France	Clinique Pasteur Lanroze	Brest
France	CH Cholet	Cholet
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Georges François Leclerc	Dijon
France	Hôpital Nord-Ouest Villefranche-sur-Saône	Gleizé
France	Centre Léon Bérard	Lyon
France	Hôpital Saint Joseph	Marseille
France	Institut Paoli Calmettes	Marseille
France	Hôpital Nord Franche Comté	Montbéliard
France	Centre Antoine Lacassagne	Nice
France	GH Diaconesses - Crois St Simon	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	Hôpital Saint Louis	Paris
France	Institut Mutualiste Montsouris	Paris
France	CHU de Poitiers	Poitiers
France	CHU - Hôpital Robert Debré	Reims
France	Institut Jean Godinot	Reims
France	CHU Rouen - Charles Nicolle	Rouen
France	ICO - Site René Gauducheau	Saint-Herblain
France	Institut de cancérologie Strasbourg Europe	Strasbourg
France	CHU Nancy - Hôpital Brabois	Vandœuvre-lès-Nancy

Sponsors (2)

Lead Sponsor	Collaborator
UNICANCER	Servier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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