Oxaliplatin ± nivolumab in combination with trifluridine/tipiracil or 5- fluorouracile ± nivolumab in frail patients with advanced, recurrent or metastatic gastric, oesophageal or gastroesophageal junction cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Jun 2023 → ongoing

Decision date (initial)

2024-06-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Servier

External identifiers

EU CT number

2024-512999-35-00

EudraCT number

2022-000273-81

ClinicalTrials.gov

NCT05476796

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to evaluate the superiority of trifluridine/tipiracil + oxaliplatin ± nivolumab over FOLFOX regimen ± nivolumab in terms of Progression-Free Survival (PFS), in first-line
palliative setting, in patients with HER 2 negative locally advanced, recurrent or metastatic gastric, oesophagus or gastroesophageal junction adenocarcinoma.

Secondary objectives 4

1. The efficacy of the treatments in terms of: • Objective Response rate (according to RECIST v1.1) (ORR) • Overall Survival (OS)
2. Safety and tolerability of treatment (NCI-CTCAE version 5.0)
3. Time to PS deterioration >2
4. The effect of treatments on Quality of Life (QoL)

Conditions and MedDRA coding

Patients with HER 2 negative locally advanced, recurrent or metastatic gastric, oesophagus or gastroesophageal junction adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

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 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 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 19

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, adjuvant immunotherapy 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
19. History of anterior organ transplant, including stem cell allograft

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 5

1. Efficacy endpoints:ORR (according to RECIST v1.1) 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
2. Efficacy endpoints : Overall survival (OS), defined as the time from date of randomisation to the date of death from any cause. Patients alive at the database cut-off date will be censored at the last date of follow-up.
3. 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.
4. Time to PS deterioration >2 defined as the time between patient randomisation and the first date when PS>2
5. Quality of Life (QoL) according to QLQ-C30 questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications