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

NCT ID: NCT07270991

Last Updated: 2025-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

324 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-31

Study Completion Date

2030-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Oeso-gastric Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

trifluridine/tipiracil

Intervention Type 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 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.

Group Type EXPERIMENTAL

trifluridine/tipiracil

Intervention Type 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.

fruquintinib

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda Development Center Americas, Inc.

INDUSTRY

Sponsor Role collaborator

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Centre Hospitalier

Aurillac, , France

Site Status

Institut Sainte Catherine

Avignon, , France

Site Status

Centre Hospitalier

Bayeux, , France

Site Status

Bayonne- Clinique Belharra

Bayonne, , France

Site Status

Centre Hospitalier Côte Basque

Bayonne, , France

Site Status

ICONE

Bezannes, , France

Site Status

BORDEAUX-Institut Bergonié

Bordeaux, , France

Site Status

Clinique Tivoli

Bordeaux, , France

Site Status

C.H.U. de Brest

Brest, , France

Site Status

Cac - François Baclesse

Caen, , France

Site Status

CHU Côte de Nacre

Caen, , France

Site Status

Ch - Jean Rougier

Cahors, , France

Site Status

Centre Hospitalier

Cholet, , France

Site Status

Saint Côme

Compiègne, , France

Site Status

Clinique de Flandre

Coudekerque-Branche, , France

Site Status

Centre Leonard de Vinci

Dechy, , France

Site Status

Institut de cancérologie de Bourgogne GRReCC

Dijon, , France

Site Status

Centre Hospitalier Emile Roux

Le Puy-en-Velay, , France

Site Status

Hôpital Franco-Britannique

Levallois-Perret, , France

Site Status

CHU Dupuytren

Limoges, , France

Site Status

Groupement Hospitalier Bretagne Sud

Lorient, , France

Site Status

Hôpital Prive Jean Mermoz

Lyon, , France

Site Status

Chu - Hôpital La Timone

Marseille, , France

Site Status

CAC Paoli Calmettes

Marseille, , France

Site Status

Confluent Sas

Nantes, , France

Site Status

CAC Antoine Lacassagne

Nice, , France

Site Status

Gh Nord Essone

Orsay, , France

Site Status

Privé - Groupe Hospitalier Diaconesses Croix Saint Simon

Paris, , France

Site Status

Chu - Aphp - Hôpital Saint Louis

Paris, , France

Site Status

Chu - Hôpital Européen Georges Pompidou

Paris, , France

Site Status

Hôpital Cochin (APHP)

Paris, , France

Site Status

Centre Hospitalier

Pau, , France

Site Status

Centre Hospitalier Saint Jean

Perpignan, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Chu - Centre Hospitalier Universitaire de Poitiers - La Miletrie

Poitiers, , France

Site Status

Clinique de La Croix du Sud

Quint-Fonsegrives, , France

Site Status

Chu - Centre Hospitalier Universitaire Robert Debre

Reims, , France

Site Status

CAC Jean Godinot

Reims, , France

Site Status

Centre Eugène Marquis

Rennes, , France

Site Status

Polyclinique

Rillieux-la-Pape, , France

Site Status

CHU - Charles Nicolle

Rouen, , France

Site Status

Clinique Mathilde

Rouen, , France

Site Status

Centre Hospitalier Prive Saint Gregoire

Saint-Grégoire, , France

Site Status

Ch Memorial France Etats Unis

Saint-Lô, , France

Site Status

Hia Begin

Saint-Mandé, , France

Site Status

Clinique Mutualiste de L'Estuaire

Saint-Nazaire, , France

Site Status

CHU de Saint Etienne - Hôpital Nord

Saint-Priest-en-Jarez, , France

Site Status

Center Hospitalier de Sens

Sens, , France

Site Status

Groupe Hospitalier Rance Emeraude

St-Malo, , France

Site Status

CAC - Paul Strauss

Strasbourg, , France

Site Status

Clinique Sainte Anne

Strasbourg, , France

Site Status

Hôpital FOCH

Suresnes, , France

Site Status

Hia Sainte Anne

Toulon, , France

Site Status

CHRU de Tours - Hopital Trousseau

Tours, , France

Site Status

CHRU Nancy Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Ch Nord Ouest

Villefranche-sur-Saône, , France

Site Status

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Site Status

KEM/Evang. Kliniken Essen Mitte gGmbH

Essen, , Germany

Site Status

Krankenhaus Nordwest GmbH

Frankfurt, , Germany

Site Status

Haematologisch Onkologische Praxis Eppendorf

Hamburg, , Germany

Site Status

Universitätsklinikum Jena

Jena, , Germany

Site Status

Uniklinikum Leipzig

Leipzig, , Germany

Site Status

Klinikum Rechts Der Isar Der Technischen Universitat Munchen

München, , Germany

Site Status

Rostock University Medical Center

Rostock, , Germany

Site Status

Countries

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France Germany

Central Contacts

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Project manager

Role: CONTACT

+33(0)3 80 66 80 13

Facility Contacts

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DANIELA BURLACU

Role: primary

04 71 46 47 41

May MABRO, MD

Role: primary

0490276268

ANNIE PEYTIER

Role: primary

02 31 51 54 17

Marjorie FAURE

Role: primary

+335 36 28 90 02

Franck AUDEMAR

Role: primary

05 59 44 33 62

William MINA

Role: primary

03 26 24 40 00

Lola Jade PALMIERI

Role: primary

05 56 33 32 78

VALERIE COCHIN

Role: primary

05 56 69 06 71

Jean-Philippe Metges, MD

Role: primary

33-2-9822-3333

Mélanie DOS SANTOS

Role: primary

02 31 45 50 02

Anne-Laure BIGNON-BRETAGNE

Role: primary

0231065437

Maher NASRI

Role: primary

05.65.20.50.21

Thomas DAVIEAU

Role: primary

0241498491

Kaïs ALDABBAGH, MD

Role: primary

Jean Baptiste AISENFARB, MD

Role: primary

NATACHA STERN-LEDIEU

Role: primary

03 20 29 59 59

Antoine DROUILLARD

Role: primary

03 80 67 30 10

Kheir Eddine BENMAMMAR

Role: primary

04 71 04 33 36

Benoist CHIBAUDEL

Role: primary

01 47 59 19 24

Frederic THUILLIER

Role: primary

05 55 05 63 96

EDWINA GIRARD

Role: primary

0297069695

Jérôme DESRAME, Pr

Role: primary

04 37 53 87 26

Laétitia DAHAN, Pr

Role: primary

+33 4 91 38 60 23

Christelle DE LA FOUCHARDIERE

Role: primary

06 64 44 05 39

Benjamin LINOT, MD

Role: primary

02 28 27 22 38

Claire JARAUDIAS

Role: primary

0492031566

Andreï HAVASI

Role: primary

0169159127

Olivier DUBREUIL, Dr

Role: primary

+33 1 44 74 28 39

Thomas APARICIO, Pr

Role: primary

0142499597

Aziz ZAANAN

Role: primary

01 49 09 50 64

Romain CORIAT

Role: primary

01 58 41 19 52

Juliette THAURY, Dr

Role: primary

05 59 92 49 83

Faiza KHEMISSA AKOUZ

Role: primary

0468616137

Chloé VENTURIN

Role: primary

04.78.86.12.91

David TOUGERON, Pr

Role: primary

+33 5 49 44 37 51

Anne-Pascale LAURENTY

Role: primary

05 32 02 72 44

Olivier BOUCHE, Pr

Role: primary

+33 3 26 78 71 72

Damien BOTSEN

Role: primary

03 26 78 71 70

Samuel LE SOURD

Role: primary

02 99 25 31 96

Matthieu SARABI

Role: primary

0481764470

Frédéric DI FIORE

Role: primary

02 32 88 86 10

Romain KOKORIAN

Role: primary

+332 32 81 15 48

Hortense DE SAINT BASILE

Role: primary

02.99.23.33.94

Dingyu XIAO

Role: primary

02 33 06 31 59

Julie LAVOLE

Role: primary

01.43.98.47.22

Manon BAVEREZ, MD

Role: primary

02 72 27 54 82

Jean-Marc PHELIP, Pr

Role: primary

04 77 82 86 19

Huu Thanh LE

Role: primary

07 50 81 80 18

Anne-Sophie MOUSSADDAQ

Role: primary

0299212226

Meher Ben ABDELGHANI

Role: primary

03 88 25 24 85

LOUIS MARIE DOURTHE

Role: primary

0388453750

Asmahane BENMAZIANE TEILLET

Role: primary

01 46 25 28 64

Caroline PRIEUX-KLOTZ

Role: primary

04 83 16 25 19

MORGANE CAULET, MD

Role: primary

02 47 47 59 00

Marie MULLER

Role: primary

0383155179

Boris MOREL, MD

Role: primary

Jack Chafic Chater Cure

Role: primary

+49 371 3330

Christian Müller

Role: primary

+49 201 1740

Thorsten GÖTZE

Role: primary

+49 69 76011

Alexander STEIN

Role: primary

40360352222

Udo Lindig

Role: primary

+49 3641 9-324201

Gertraud Stocker

Role: primary

+49 341 97109

Sylvie Lorenzen

Role: primary

+49 89 41400

Hartmut GLÄSER

Role: primary

+49 381 4940

Other Identifiers

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2025-522395-92-00

Identifier Type: CTIS

Identifier Source: secondary_id

ENGIC06-PRODIGE114-FRUQUITAS

Identifier Type: -

Identifier Source: org_study_id

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