ENGIC 06 (PRODIGE 114) – FFCD 2401 – FRUQUITAS Randomized phase III trial to compare trifluridine/tipiracil + Fruquintinib versus trifluridine/tipiracil alone for metastatic oeso-gastric adenocarcinoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Dec 2025 → ongoing

Decision date (initial)

2025-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

TAKEDA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare OS between trifluridine/tipiracil plus fruquintinib (Arm B) versus trifluridine/tipiracil alone (Arm A)

Secondary objectives 5

1. progression-free survival (PFS)
2. time to progression (TTP)
3. objective response rate (ORR) and disease control rate (DCR)
4. safety profile according to NCI-CTCAE v5.0
5. quality of life (QoL) according EORTC QLQ - C30 and STO22

Conditions and MedDRA coding

metastatic oeso-gastric adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Age ≥ 18 years (patients enrolled gender independently).
2. Histologically proven metastatic adenocarcinoma of the stomach or the esophagogastric junction (GEJ) or esophagus.
3. Prior treatment by two or three lines of treatment for metastatic setting (patients who received adjuvant therapy and developed metastatic disease within 6 months of completing treatment should be considered as having failed first-line therapy for metastatic disease).
4. Prior treatment (progression or intolerance) with platinum salts (oxaliplatin or cisplatin), fluoropyrimidine and irinotecan and/or taxane (+/- anti-HER2 agents +/- immune checkpoint inhibitors +/- ramucirumab +/- anti-claudin 18.2).
5. Measurable or non-measurable lesions. (Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
6. World Health Organisation (WHO) performance status 0-1.
7. Adequate organ function: ANC ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dL, platelets ≥ 100 G/L, AST/ALT ≤ 3 x ULN (≤ 5 x ULN in case of liver metastase(s)), total bilirubin ≤ 1.5 x ULN, creatinine clearance > 30 mL/min (CKD EPI).
8. Adequate coagulation tests (INR and activated partial thromboplastin time (APTT) ≤1.5 × ULN) unless the patient is receiving anticoagulant therapy.
9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
10. Man and woman of childbearing potential agrees to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 6 months after the last treatment intake.
11. Patient is able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures performed.
12. Available tumor block (surgical specimens of primary tumor and if not available tumor biopsies).
13. Patient willing to participate to biological studies

Exclusion criteria 23

1. Concurrent enrolment in another clinical study – unless it is an observational study or during the follow-up for survival status update only of an interventional study.
2. Administration of the last dose of anticancer therapy and palliative radiotherapy ≤ 2 weeks prior to the first dose of study drug.
3. Current or prior bowel obstruction within 28 days before the first dose of study drugs.
4. Any unresolved clinical significant toxicity NCI CTCAE v5.0 ≥ grade 2 from previous anticancer therapy (except neuropathy).
5. More than 3 prior lines of treatment
6. Major surgical procedure (e.g. exploratory laparoscopy is not considered as a major surgical procedure) within 2 weeks prior to the first dose of treatment.
7. History of leptomeningeal carcinomatosis or symptomatic or untreated brain metastase(s). Patients whose brain metastase(s) have been treated may participate if any neurologic symptoms that developed as a result of the brain metastases are resolved or stable.
8. Severe cardiac disorders (including but not limited to acute myocardial infarction, stroke, unstable angina, NYHA class III/IV heart failure, or LVEF<50%) within 6 months.
9. Severe liver dysfunction (cirrhosis Child Pugh B or C).
10. Gastric or duodenal active ulcer
11. Thromboembolic events (including deep vein thrombosis and pulmonary embolism) in the past 6 months
12. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled hypertension (defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg despite optimal medical management), interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea
13. Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
14. Patients with urine protein test 2+ or more and 24 hours urine protein>=1.0g/24h.
15. Known positive test for HIV, active hepatitis B or hepatitis C, active tuberculosis.
16. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. (excipients with known effects and potential risk of allergies : tartrazine (E102) ,sunset yellow FCF (E110), Lactose monohydrate).
17. Prior treatment with trifluridine/tipiracil and/or fruquintinib and/or regorafenib and/or any anti-VEGFR tyrosine kinase inhibitor.
18. Active infection requiring intravenous antibiotics at the time of Day 1 of Cycle 1.
19. Other malignancy within 3 years prior to study enrolment, except for localized cancer in situ, basal or squamous cell skin cancer or other localized tumor with complete resection.
20. Treatment with powerful CYP 450 inducers (no contraindication for inhibitors)
21. Pregnant or breastfeeding female patient
22. Congenital galactosemia, total lactase deficiency (lactose intolerance) or glucose-galactose malabsorption syndrome.
23. Patients with clinically significant bleeding within the past 2 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) and is defined as the time between the date of randomization and the date of death caused by any reason or the date of last news if the patient is alive.

Secondary endpoints 5

1. Progression-free survival (PFS) is defined as the time between date of randomization and the date of first radiological progression according to RECIST 1.1 or death (whichever occurs first). Patients alive without progression will be censored to the date of last radiologic assessment.
2. Time to progression (TTP) is defined as the time between date of randomization and the date of first radiological progression (according to RECIST v1.1). Patients without progression will be censored at date of last radiologic assessment or date of death. The death will not be considered as an event
3. Best Objective response rate (ORR) and disease control rate (DCR) is defined as incidence of a complete or partial response during treatment for ORR and a complete or partial or a stability for DCR. ORR and DCR will be provided as overall best response and at 2, 3, 6 and 9 months.
4. Safety profile: TEAEs will be graded according to the NCI-CTCAE v5.0 classifications.
5. Quality of life (QoL) will be evaluated using EORTC QLQ-C30 and the STO22 questionnaires.

Investigational products

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

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Coordinator

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Coordinator

Third parties 3

Locations

3 EU/EEA countries · 78 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 35 files

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

Application history

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