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

Phase 1

• Conditions: Patients with gastric, oesophagus or gastroesophageal junction adenocarcinoma locally advanced, recurrent or metastatic, ineligible for triplet chemotherapy.; MedDRA version: 21.0Level: PTClassification code 10030137Term: Oesophageal adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10001150Term: Adenocarcinoma gastricSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10066354Term: Adenocarcinoma of the gastroesophageal junctionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2022-000273-81-FR
• Lead Sponsor: ICANCER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-07-13
• Last Update Posted: 24 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 118

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 <30 g/L)
- Other criterion left at investigator’s discretion (this later must be filled in by the investigator).
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified