Trifluridine/Tipiracil + Fruquintinib Versus Trifluridine/Tipiracil Alone for Metastatic Oeso-gastric Adenocarcinoma

NCT07270991 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: ENGIC06-PRODIGE114-FRUQUITAS2025-522395-92-00
• Study Type: interventional
• Target: 324
• Locations: 2 countries
• Sites: 64

Brief Summary

Advanced cancer of the stomach and the gastro-esophageal junction (G/GEJ) remains a very serious disease. Today, only about 10-15% of patients are alive after 5 years. Treatments mainly aim to control symptoms, extend life, and maintain quality of life. First treatments usually combine two chemotherapies, but recent years have brought real progress. Immunotherapy - drugs that "unlock" the immune system - has shown clear benefits. For patients whose tumors have certain markers (like PD-L1), combining drugs such as nivolumab or pembrolizumab with chemotherapy can help patients live longer. Another breakthrough is zolbetuximab, a targeted therapy that attacks a protein (Claudin 18.2) found on many gastric cancers, also improving survival. When cancer grows despite these therapies, second-line treatments are used. The most common is chemotherapy with paclitaxel + ramucirumab, which blocks the tumor's blood supply. These drugs extend survival, but usually only by a few months. For patients who need a third option, the oral drug trifluridine/tipiracil (TAS-102) can provide extra time, though benefits remain limited. That's why researchers are now exploring combinations. Since stomach tumors rely on forming new blood vessels, combining trifluridine/tipiracil with anti-angiogenic drugs - medicines that cut off the tumor's blood supply - looks promising. One of the most exciting of these drugs is fruquintinib, already proven effective in colorectal cancer. A new international trial, FRUQUITAS (ENGIC 06/PRODIGE 114), is now testing whether adding fruquintinib to trifluridine/tipiracil can improve survival for patients with advanced stomach or gastro-esophageal cancer.

Conditions

Metastatic Oesogastric Adenocarcinoma

Keywords

Cancer; Fruquintinib; oeso-gastric; third line

Outcome Measures

Primary Outcomes (1)

• Overall survival

  The primary endpoint is the 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.

  up to 18 months after randomization

Secondary Outcomes (1)

• Progression-free survival (PFS)

  Up 18 months after randomization

Study Arms (2)

Arm A (control arm): trifluridine/tipiracil

ACTIVE COMPARATOR

Cycle of 28 days 35 mg/m2 by mouth twice daily on Days 1 to 5, 2 days of rest and 35 mg/m2 by mouth twice daily on days 8 to 12

Drug: trifluridine/tipiracil

Arm B (experimental arm): trifluridine/tipiracil + fruquintinib

EXPERIMENTAL

Cycle of 28 days For trifluridine/tipiracil: 35 mg/m2 by mouth twice daily on Day 1 to 5, 2 days of rest and 35 mg/m2 by mouth twice daily on days 8 to 12 For fruquintinib: 5 mg by mouth once daily Day 1 to Day 21 (3 weeks) Treatment will be repeated every 4 weeks until radiological disease progression, unacceptable toxicity or patient's refusal.

Drug: trifluridine/tipiracil; Drug: fruquintinib

Interventions

trifluridine/tipiracil DRUG

Cycle of 28 days 35 mg/m2 by mouth twice daily on Days 1 to 5, 2 days of rest and 35 mg/m2 by mouth twice daily on days 8 to 12 Treatment will be repeated every 4 weeks until radiological disease progression, unacceptable toxicity or patient's refusal.

Arm A (control arm): trifluridine/tipiracil; Arm B (experimental arm): trifluridine/tipiracil + fruquintinib

fruquintinib DRUG

For fruquintinib: 5 mg by mouth once daily Day 1 to Day 21 (3 weeks) Treatment will be repeated every 4 weeks until radiological disease progression, unacceptable toxicity or patient's refusal.

Arm B (experimental arm): trifluridine/tipiracil + fruquintinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years (patients enrolled gender independently).
• Histologically proven metastatic adenocarcinoma of the stomach or the esophagogastric junction (GEJ) or esophagus.
• 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).
• 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).
• Measurable or non-measurable lesions. (Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
• World Health Organisation (WHO) performance status 0-1.
• 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).
• Adequate coagulation tests (INR and activated partial thromboplastin time (APTT) ≤1.5 × ULN) unless the patient is receiving anticoagulant therapy.
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
• 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 (use contraceptive methods that result in a failure rate of \<1% per year) during the study and for 6 months after the last treatment intake.
• Patient is able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures performed.
• Available tumor block (surgical specimens of primary tumor and if not available tumor biopsies).
• Patient willing to participate to biological studies.

You may not qualify if:

• 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.
• Administration of the last dose of anticancer therapy and palliative radiotherapy ≤ 2 weeks prior to the first dose of study drug.
• Current or prior bowel obstruction within 28 days before the first dose of study drugs.
• Any unresolved clinical significant toxicity NCI CTCAE v5.0 ≥ grade 2 from previous anticancer therapy (except neuropathy).
• More than 3 prior lines of treatment.
• 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.
• 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.
• 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.
• Severe liver dysfunction (cirrhosis Child Pugh B or C).
• Gastric or duodenal active ulcer.
• Thromboembolic events (including deep vein thrombosis and pulmonary embolism) in the past 6 months
• 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,
• 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.
• Patients with urine protein test 2+ or more and 24 hours urine protein≥1.0g/24h.
• Known positive test for HIV, active hepatitis B or hepatitis C, active tuberculosis.

Sponsors & Collaborators

• Takeda Development Center Americas, Inc.: collaborator
• Federation Francophone de Cancerologie Digestive: lead

Study Sites (64)

Centre Hospitalier

Aurillac, France

NOT YET RECRUITING

Institut Sainte Catherine

Avignon, 84000, France

NOT YET RECRUITING

Centre Hospitalier

Bayeux, France

NOT YET RECRUITING

Bayonne- Clinique Belharra

Bayonne, France

NOT YET RECRUITING

Centre Hospitalier Côte Basque

Bayonne, France

NOT YET RECRUITING

ICONE

Bezannes, France

NOT YET RECRUITING

BORDEAUX-Institut Bergonié

Bordeaux, France

NOT YET RECRUITING

Clinique Tivoli

Bordeaux, France

NOT YET RECRUITING

C.H.U. de Brest

Brest, 29200, France

NOT YET RECRUITING

Cac - François Baclesse

Caen, France

NOT YET RECRUITING

CHU Côte de Nacre

Caen, France

NOT YET RECRUITING

Ch - Jean Rougier

Cahors, France

NOT YET RECRUITING

Centre Hospitalier

Cholet, France

NOT YET RECRUITING

Saint Côme

Compiègne, France

NOT YET RECRUITING

Clinique de Flandre

Coudekerque-Branche, France

NOT YET RECRUITING

Centre Leonard de Vinci

Dechy, France

NOT YET RECRUITING

Institut de cancérologie de Bourgogne GRReCC

Dijon, France

NOT YET RECRUITING

Centre Hospitalier Emile Roux

Le Puy-en-Velay, France

NOT YET RECRUITING

Hôpital Franco-Britannique

Levallois-Perret, France

NOT YET RECRUITING

CHU Dupuytren

Limoges, France

NOT YET RECRUITING

Groupement Hospitalier Bretagne Sud

Lorient, France

NOT YET RECRUITING

Hôpital Prive Jean Mermoz

Lyon, 69008, France

NOT YET RECRUITING

Chu - Hôpital La Timone

Marseille, 13385, France

NOT YET RECRUITING

CAC Paoli Calmettes

Marseille, France

NOT YET RECRUITING

Confluent Sas

Nantes, France

NOT YET RECRUITING

CAC Antoine Lacassagne

Nice, France

NOT YET RECRUITING

Gh Nord Essone

Orsay, France

NOT YET RECRUITING

Privé - Groupe Hospitalier Diaconesses Croix Saint Simon

Paris, 75020, France

NOT YET RECRUITING

Chu - Aphp - Hôpital Saint Louis

Paris, 75475, France

NOT YET RECRUITING

Chu - Hôpital Européen Georges Pompidou

Paris, France

NOT YET RECRUITING

Hôpital Cochin (APHP)

Paris, France

NOT YET RECRUITING

Centre Hospitalier

Pau, 64046, France

NOT YET RECRUITING

Centre Hospitalier Saint Jean

Perpignan, France

NOT YET RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

NOT YET RECRUITING

Chu - Centre Hospitalier Universitaire de Poitiers - La Miletrie

Poitiers, 86021, France

RECRUITING

Clinique de La Croix du Sud

Quint-Fonsegrives, France

NOT YET RECRUITING

Chu - Centre Hospitalier Universitaire Robert Debre

Reims, 51092, France

NOT YET RECRUITING

CAC Jean Godinot

Reims, France

NOT YET RECRUITING

Centre Eugène Marquis

Rennes, France

NOT YET RECRUITING

Polyclinique

Rillieux-la-Pape, France

NOT YET RECRUITING

CHU - Charles Nicolle

Rouen, France

NOT YET RECRUITING

Clinique Mathilde

Rouen, France

NOT YET RECRUITING

Centre Hospitalier Prive Saint Gregoire

Saint-Grégoire, France

NOT YET RECRUITING

Ch Memorial France Etats Unis

Saint-Lô, France

NOT YET RECRUITING

Hia Begin

Saint-Mandé, France

NOT YET RECRUITING

Clinique Mutualiste de L'Estuaire

Saint-Nazaire, France

NOT YET RECRUITING

CHU de Saint Etienne - Hôpital Nord

Saint-Priest-en-Jarez, 42270, France

NOT YET RECRUITING

Center Hospitalier de Sens

Sens, 89108, France

NOT YET RECRUITING

Groupe Hospitalier Rance Emeraude

St-Malo, France

NOT YET RECRUITING

CAC - Paul Strauss

Strasbourg, France

NOT YET RECRUITING

Clinique Sainte Anne

Strasbourg, France

NOT YET RECRUITING

Hôpital FOCH

Suresnes, France

NOT YET RECRUITING

Hia Sainte Anne

Toulon, France

NOT YET RECRUITING

CHRU de Tours - Hopital Trousseau

Tours, 37044, France

NOT YET RECRUITING

CHRU Nancy Brabois

Vandœuvre-lès-Nancy, France

NOT YET RECRUITING

Ch Nord Ouest

Villefranche-sur-Saône, France

NOT YET RECRUITING

Klinikum Chemnitz gGmbH

Chemnitz, Germany

NOT YET RECRUITING

KEM/Evang. Kliniken Essen Mitte gGmbH

Essen, Germany

NOT YET RECRUITING

Krankenhaus Nordwest GmbH

Frankfurt, Germany

NOT YET RECRUITING

Haematologisch Onkologische Praxis Eppendorf

Hamburg, Germany

NOT YET RECRUITING

Universitätsklinikum Jena

Jena, Germany

NOT YET RECRUITING

Uniklinikum Leipzig

Leipzig, Germany

NOT YET RECRUITING

Klinikum Rechts Der Isar Der Technischen Universitat Munchen

München, Germany

NOT YET RECRUITING

Rostock University Medical Center

Rostock, Germany

NOT YET RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

trifluridine tipiracil drug combination; HMPL-013

Central Study Contacts

Project manager

CONTACT

+33(0)3 80 66 80 13; prodige114.fruquitas@ffcd.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 8, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): November 30, 2030
• Study Completion (Estimated): November 30, 2030
• Last Updated: February 5, 2026

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8); FR (56)