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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
118
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 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.
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
Clinique de l'Europe
Amiens, France
NOT_YET_RECRUITINGHopital Privé Arras Les Bonnettes
Arras, France
RECRUITINGInstitut Sainte Catherine
Avignon, France
RECRUITINGCentre Hospitalier de Beauvais
Beauvais, France
RECRUITINGCHU Besançon - Hôpital Jean Minjoz
Besançon, France
RECRUITINGCHU Morvan
Brest, France
RECRUITINGClinique Pasteur Lanroze
Brest, France
NOT_YET_RECRUITINGCH Cholet
Cholet, France
RECRUITINGCentre Jean Perrin
Clermont-Ferrand, France
RECRUITINGCHU d'Estaing
Clermont-Ferrand, France
RECRUITING...and 19 more locations
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.
Time frame: From randomization to disease progression or death up to 5 years
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).
Time frame: 5 years
Overall survival
The overall survival (OS) is the length of time from randomization that patients enrolled in the study are still alive.
Time frame: 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.
Time frame: 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").
Time frame: 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.
Time frame: From baseline until disease progression, up to 1 year
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