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

February 3, 2026 updated by: Federation Francophone de Cancerologie Digestive

Randomized Phase III Trial to Compare Trifluridine/Tipiracil + Fruquintinib Versus Trifluridine/Tipiracil Alone for Metastatic Oeso-gastric Adenocarcinoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

324

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Aurillac, France
        • Not yet recruiting
        • Centre Hospitalier
        • Contact:
        • Principal Investigator:
          • Daniela BERLACU
      • Avignon, France, 84000
        • Not yet recruiting
        • Institut Sainte Catherine
        • Principal Investigator:
          • May MABRO
        • Contact:
      • Bayeux, France
        • Not yet recruiting
        • Centre Hospitalier
        • Contact:
        • Principal Investigator:
          • Annie PEYTIER
      • Bayonne, France
        • Not yet recruiting
        • Bayonne- Clinique Belharra
        • Contact:
        • Principal Investigator:
          • Marjorie FAURE
      • Bayonne, France
        • Not yet recruiting
        • Centre Hospitalier Côte Basque
        • Principal Investigator:
          • Franck Audemar
        • Contact:
      • Bezannes, France
        • Not yet recruiting
        • ICONE
        • Contact:
        • Principal Investigator:
          • WILLIAM MINA
      • Bordeaux, France
        • Not yet recruiting
        • Clinique Tivoli
        • Contact:
        • Principal Investigator:
          • Valérie COCHIN
      • Bordeaux, France
        • Not yet recruiting
        • BORDEAUX-Institut Bergonié
        • Contact:
        • Principal Investigator:
          • Lola Jade PALMIERI
      • Brest, France, 29200
        • Not yet recruiting
        • C.H.U. de Brest
        • Principal Investigator:
          • Jean-Philippe Metges
        • Contact:
      • Caen, France
        • Not yet recruiting
        • CHU Côte de Nacre
        • Contact:
        • Principal Investigator:
          • Anne-Laure BIGNON-BRETAGNE
      • Caen, France
        • Not yet recruiting
        • Cac - François Baclesse
        • Contact:
        • Principal Investigator:
          • Mélanie DOS SANTOS
      • Cahors, France
        • Not yet recruiting
        • Ch - Jean Rougier
        • Contact:
        • Principal Investigator:
          • Maher NASRI
      • Cholet, France
        • Not yet recruiting
        • Centre Hospitalier
        • Contact:
        • Principal Investigator:
          • Thomas DAVIEAU
      • Compiègne, France
        • Not yet recruiting
        • Saint Côme
        • Principal Investigator:
          • Kaïs ALDABBAGH
        • Contact:
      • Coudekerque-Branche, France
        • Not yet recruiting
        • Clinique de Flandre
        • Principal Investigator:
          • Jean-Baptiste AISENFARB
        • Contact:
      • Dechy, France
        • Not yet recruiting
        • Centre Leonard de Vinci
        • Contact:
        • Principal Investigator:
          • NATACHA STERN-LEDIEU
      • Dijon, France
        • Not yet recruiting
        • Institut de cancérologie de Bourgogne GRReCC
        • Principal Investigator:
          • Antoine DROUILLARD
        • Contact:
      • Le Puy-en-Velay, France
        • Not yet recruiting
        • Centre Hospitalier Emile Roux
        • Contact:
        • Principal Investigator:
          • Kheir Eddine BENMAMMAR
      • Levallois-Perret, France
        • Not yet recruiting
        • Hôpital Franco-Britannique
        • Principal Investigator:
          • Benoist CHIBAUDEL
        • Contact:
      • Limoges, France
        • Not yet recruiting
        • Chu Dupuytren
        • Principal Investigator:
          • Frédéric THUILLIER
        • Contact:
      • Lorient, France
        • Not yet recruiting
        • Groupement Hospitalier Bretagne Sud
        • Contact:
        • Principal Investigator:
          • EDWINA GIRARD
      • Lyon, France, 69008
        • Not yet recruiting
        • Hopital Prive Jean Mermoz
        • Principal Investigator:
          • Jérôme DESRAME
        • Contact:
      • Marseille, France, 13385
        • Not yet recruiting
        • Chu - Hôpital La Timone
        • Contact:
        • Principal Investigator:
          • Laétitia DAHAN
      • Marseille, France
        • Not yet recruiting
        • CAC Paoli Calmettes
        • Principal Investigator:
          • Christelle DE LA FOUCHARDIERE
        • Contact:
      • Nantes, France
        • Not yet recruiting
        • Confluent Sas
        • Contact:
        • Principal Investigator:
          • Benjamin LINOT
      • Nice, France
        • Not yet recruiting
        • CAC Antoine Lacassagne
        • Contact:
        • Principal Investigator:
          • Claire JARAUDIAS
      • Orsay, France
        • Not yet recruiting
        • Gh Nord Essone
        • Contact:
        • Principal Investigator:
          • Andreï HAVASI
      • Paris, France, 75020
        • Not yet recruiting
        • Privé - Groupe Hospitalier Diaconesses Croix Saint Simon
        • Principal Investigator:
          • Olivier DUBREUIL
        • Contact:
      • Paris, France, 75475
        • Not yet recruiting
        • Chu - Aphp - Hôpital Saint Louis
        • Principal Investigator:
          • Thomas APARICIO
        • Contact:
      • Paris, France
        • Not yet recruiting
        • Chu - Hôpital Européen Georges Pompidou
        • Contact:
        • Principal Investigator:
          • Aziz ZAANAN
      • Paris, France
        • Not yet recruiting
        • Hôpital Cochin (APHP)
        • Principal Investigator:
          • ROMAIN CORIAT
        • Contact:
      • Pau, France, 64046
        • Not yet recruiting
        • Centre Hospitalier
        • Contact:
        • Principal Investigator:
          • Juliette THAURY
      • Perpignan, France
        • Not yet recruiting
        • Centre Hospitalier Saint Jean
        • Principal Investigator:
          • Faiza KHEMISSA AKOUZ
        • Contact:
      • Pierre-Bénite, France, 69495
        • Not yet recruiting
        • Centre Hospitalier Lyon Sud
        • Contact:
        • Principal Investigator:
          • Chloé VENTURIN
      • Poitiers, France, 86021
        • Recruiting
        • Chu - Centre Hospitalier Universitaire de Poitiers - La Miletrie
        • Principal Investigator:
          • David TOUGERON
        • Contact:
      • Quint-Fonsegrives, France
        • Not yet recruiting
        • Clinique de la Croix du Sud
        • Principal Investigator:
          • Anne-Pascale LAURENTY
        • Contact:
      • Reims, France, 51092
        • Not yet recruiting
        • Chu - Centre Hospitalier Universitaire Robert Debre
        • Contact:
        • Principal Investigator:
          • Olivier BOUCHE
      • Reims, France
        • Not yet recruiting
        • CAC Jean Godinot
        • Principal Investigator:
          • Damien BOTSEN
        • Contact:
      • Rennes, France
        • Not yet recruiting
        • Centre Eugene Marquis
        • Principal Investigator:
          • Samuel LE SOURD
        • Contact:
      • Rillieux-la-Pape, France
        • Not yet recruiting
        • Polyclinique
        • Principal Investigator:
          • Matthieu SARABI
        • Contact:
      • Rouen, France
        • Not yet recruiting
        • Clinique Mathilde
        • Contact:
        • Principal Investigator:
          • Romain KOKORIAN
      • Rouen, France
        • Not yet recruiting
        • CHU - Charles Nicolle
        • Principal Investigator:
          • Frédéric DI FIORE
        • Contact:
      • Saint-Grégoire, France
        • Not yet recruiting
        • Centre Hospitalier Privé Saint Grégoire
        • Contact:
        • Principal Investigator:
          • Hortense DE SAINT BASILE
      • Saint-Lô, France
        • Not yet recruiting
        • Ch Memorial France Etats Unis
        • Contact:
        • Principal Investigator:
          • Dingyu XIAO
      • Saint-Mandé, France
        • Not yet recruiting
        • HIA Begin
        • Contact:
        • Principal Investigator:
          • Julie LAVOLE
      • Saint-Nazaire, France
        • Not yet recruiting
        • Clinique Mutualiste de l'Estuaire
        • Contact:
        • Principal Investigator:
          • Manon BAVEREZ
      • Saint-Priest-en-Jarez, France, 42270
        • Not yet recruiting
        • CHU de Saint Etienne - Hopital Nord
        • Principal Investigator:
          • Jean-Marc PHELIP
        • Contact:
      • Sens, France, 89108
        • Not yet recruiting
        • Center Hospitalier de Sens
        • Contact:
        • Principal Investigator:
          • Huu Thanh LE
      • St-Malo, France
        • Not yet recruiting
        • Groupe Hospitalier Rance Emeraude
        • Contact:
        • Principal Investigator:
          • Anne-Sophie MOUSSADDAQ
      • Strasbourg, France
      • Strasbourg, France
        • Not yet recruiting
        • Clinique Sainte Anne
        • Principal Investigator:
          • LOUIS MARIE DOURTHE
        • Contact:
      • Suresnes, France
        • Not yet recruiting
        • Hopital Foch
        • Contact:
        • Principal Investigator:
          • Asmahane BENMAZIANE TEILLET
      • Toulon, France
        • Not yet recruiting
        • HIA Sainte Anne
        • Principal Investigator:
          • Caroline PRIEUX-KLOTZ
        • Contact:
      • Tours, France, 37044
        • Not yet recruiting
        • CHRU de Tours - Hopital Trousseau
        • Contact:
        • Principal Investigator:
          • Morgane CAULET
      • Vandœuvre-lès-Nancy, France
        • Not yet recruiting
        • CHRU Nancy Brabois
        • Contact:
        • Principal Investigator:
          • Marie MULLER
      • Villefranche-sur-Saône, France
        • Not yet recruiting
        • Ch Nord Ouest
        • Contact:
        • Principal Investigator:
          • Boris MOREL
  • Germany
      • Chemnitz, Germany
        • Not yet recruiting
        • Klinikum Chemnitz gGmbH
        • Contact:
          • Jack Chafic Chater Cure
          • Phone Number: +49 371 3330
          • Email: juhle@uke.de
        • Principal Investigator:
          • Jack Chafic Chater Cure
      • Essen, Germany
        • Not yet recruiting
        • KEM/Evang. Kliniken Essen Mitte gGmbH
        • Principal Investigator:
          • Christian Müller
        • Contact:
      • Frankfurt, Germany
        • Not yet recruiting
        • Krankenhaus Nordwest GmbH
        • Principal Investigator:
          • Thorsten Götze
        • Contact:
      • Hamburg, Germany
        • Not yet recruiting
        • Haematologisch Onkologische Praxis Eppendorf
        • Contact:
        • Principal Investigator:
          • Alexander STEIN
      • Jena, Germany
        • Not yet recruiting
        • Universitatsklinikum Jena
        • Principal Investigator:
          • Udo Lindig
        • Contact:
      • Leipzig, Germany
        • Not yet recruiting
        • Uniklinikum Leipzig
        • Principal Investigator:
          • Gertraud Stocker
        • Contact:
      • München, Germany
        • Not yet recruiting
        • Klinikum Rechts Der Isar Der Technischen Universität München
        • Principal Investigator:
          • Sylvie Lorenzen
        • Contact:
      • Rostock, Germany
        • Not yet recruiting
        • Rostock University Medical Center
        • Contact:
        • Principal Investigator:
          • Hartmut GLÄSER

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  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 (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.
  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:

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A (control arm): trifluridine/tipiracil
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
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.
Experimental: Arm B (experimental arm): trifluridine/tipiracil + fruquintinib

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
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.
Drug: fruquintinib
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: up to 18 months after randomization
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: Up 18 months after randomization
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.
Up 18 months after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federation Francophone de Cancerologie Digestive

Collaborators

Takeda Development Center Americas, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2025

Primary Completion (Estimated)

November 30, 2030

Study Completion (Estimated)

November 30, 2030

Study Registration Dates

First Submitted

November 24, 2025

First Submitted That Met QC Criteria

December 5, 2025

First Posted (Actual)

December 8, 2025

Study Record Updates

Last Update Posted (Actual)

February 5, 2026

Last Update Submitted That Met QC Criteria

February 3, 2026

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ENGIC06-PRODIGE114-FRUQUITAS
  • 2025-522395-92-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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