Patients with gastric, oesophagus or gastroesophageal junction adenocarcinoma locally advanced, recurrent or metastatic, ineligible for triplet chemotherapy. MedDRA version: 21.0 Level: PT Classification code 10030137 Term: Oesophageal adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10001150 Term: Adenocarcinoma gastric System Organ Class: 10029104 - Neoplasms benign, malignant
Conditions
Interventions
Trade Name: LONSURF
Product Name: LONSURF
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Trifluridine/Tipiracil
CAS Number: 733030-01-8
Other descriptive name: TIPIRACIL HYDROCHLORIDE MIXTURE
Sponsors
UNICANCER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed locally advanced, recurrent or metastatic adenocarcinoma of the stomach, oesophagus or gastroesophageal junction (GEJ). 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 CPS PD-L1 score (result in % with the name of the method used). The microsatellite and 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, defined with ONE of the following criteria: - ECOG-PS=2 - Age =70 year old PLUS one frailty criteria on ADL/IADL score - Denutrition (defined by albumin 40 mL/min 9. No Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia =65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: 1. Other current or previous malignancy within the past 3 years (with the exception of squamous cell carcinoma of the skin treated by surgery). 2. Adjuvant chemotherapy or radio-chemotherapy completed for less than 6 months. 3. Peripheral neuropathy of NCI-CTCAE grade =2 at baseline. 4. Patients with known allergy or severe hypersensitivity to any of the trial drugs or any of the trial drug excipients. 5. 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. 6. Previous treatment with trifluridine/tipiracil. 7. Known Human Immunodeficiency Virus (HIV) infection. 8. Active Hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen [HBsAg] test prior to inclusion) or hepatitis C virus (HCV). 9. Interstitial lung disease. 10. Prior pneumonitis requiring systemic corticosteroid therapy. 11. Active infections. 12. Pregnant or breastfeeding woman. 13. Participation in another therapeutic trial within the 30 days prior to randomisation. 14. Persons deprived of their liberty or under protective custody or guardianship. 15. Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the superiority of trifluridine/tipiracil + oxaliplatin over FOLFOX regimen in terms of Progression-Free Survival (PFS), in first-line palliative setting, in patients with gastric, oesophagus or gastroesophageal junction adenocarcinoma locally advanced, recurrent or metastatic, ineligible for triplet chemotherapy.;Secondary Objective: - The efficacy of the treatments in terms of: • Objective Response rate (according to RECIST v1.1) (ORR) • Overall Survival (OS) - Safety and tolerability of treatment (NCI-CTCAE version 5.0) - Time to PS deterioration >2 - The effect of treatments on Quality of Life (QoL);Primary end point(s): PFS defined as the time from the date of randomisation to date of disease progression (radiological or clinical) or death from any cause, whichever occurs first. Patients without tumour progression or death at the time of analysis will be censored at the date of their last tumour assessment.;Timepoint(s) of evaluation of this end point: The primary endpoint of the study is the PFS defined as the time from the date of randomisation to date of disease progression (radiological or clinical) or death from any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: • ORR (according to RECIST v1.1 criteria) defined as the percentage of patients with Complete Response (CR) or Partial Response (PR). Patients who discontinue treatment without a tumour assessment will be considered non-responders for the analysis • Overall survival (OS), defined as the time from date of randomisation to the date of death from any cause. If a patient is alive at the database cut-off date, then the patient will be censored at the last date of follow-up. - Safety and tolerability of treatment (NCI-CTCAE version 5.0) determined through the incidence of adverse events, treatment related adverse events, serious adverse Events (SAE), and death. - Time to PS deterioration >2 defined as the time between patient randomisation and date when PS>2 - Quality of Life (QoL) according to QLQ-C30 questionnaire - Ancillary studies will address: • Specific pathological features and expression of biomarkers: microsatellite status (MS), PD1 and PDL1 expression, TMB, CD8+ cell infiltration, Epstein Barr Virus (assessed by in situ hybridization), TP53, E-cadherin, HER3. • Circulating DNA and its value for prognosis and treatment monitoring (monitoring of DNA levels at different point during the treatment: pretreatment ctDNA and then every two months during the first year). Genetic changes will also be evaluated in several genes. ;Timepoint(s) of evaluation of this end point: -Efficacy endpoints: Evaluation every 8 weeks from D1C5 till disease progression - Safety and tolerability of treatment (NCI-CTCAE version 5.0) During all the study - Quality of Life (QoL) according to QLQ-C30 questionnaire Every 8 weeks from D1C5 till disease progression | — |
Countries
France
Contacts
Public ContactAIT RAHMOUNE
unicancer
Outcome results
None listed