Evaluation of Efficacy of Trifluridine/Tipiracil Plus an Anti-IL-1α True Human Antibody Versus Trifluridine/Tipiracil Plus Placebo in Metastatic Colorectal Cancer Patients After Failure of Oxaliplatin, Irinotecan, Fluoropyrimidine

NCT05201352 | Active Not Recruiting Phase 1

• 1 other identifier: 2020-004601-31
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 14

Brief Summary

Unresectable metastatic colorectal cancer (mCRC) remains an incurable disease. After failure of conventional treatments involving fluoropyrimidines, oxaliplatin and irinotecan in combination or not with biotherapies targeting EGFR and VEGF; regorafenib shows a modest improvement in overall survival. Recently, trifluridine/tipiracil has also shown efficacy in phase 3 with an overall survival of around 7 months. Trifluridine/tipiracil has become the standard of care for advanced mCRC in most western countries. However, the objective response rate remains very low and the survival gain remains moderate (+2 months). Therefore, new strategies are needed to ensure that mCRC patients who have received multiple lines of therapy can receive more effective treatments. Based on previous clinical trials on IL-1 inhibition and our preclinical data, IL-1 inhibition may increase the efficacy of trifluridine/tipiracil. The goal is to test whether the addition of XB2001 to trifluridine/tipiracil could be synergistic.

Conditions

Metastatic Colorectal Cancer

Keywords

trifluridine/tipiracil; anti-IL-1α True Human antibody; phase I/II

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of XB2001

  At the end of Cycle 1 (each cycle is 28 days)

• Overall survival

  6-month

Study Arms (2)

Experimental arm

EXPERIMENTAL

trifluridine/tipiracil + XB2001

Drug: trifluridine/tipiracil + XB2001

Control arm

PLACEBO COMPARATOR

trifluridine/tipiracil + placebo

Drug: trifluridine/tipiracil + placebo

Interventions

trifluridine/tipiracil + XB2001 DRUG

trifluridine/tipiracil every 28 days + XB2001 1000mg intravenous infusion every 2 weeks

Experimental arm

trifluridine/tipiracil + placebo DRUG

trifluridine/tipiracil every 28 days + Placebo intravenous infusion every 2 weeks

Control arm

Eligibility Criteria

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

You may qualify if:

• Male or female that must have signed a written informed consent prior to any study specific procedures
• Aged ≥ 18 years at randomization
• Patient with histologically proven metastatic colorectal cancer previously treated for metastatic disease by chemotherapy treatment including oxaliplatin, irinotecan, fluoropyrimidine, antiangiogenic (anti-VEGF: bevacizumab or aflibercept) and anti-EGFR (cetuximab or panitumumab) if indicated (MSI tumor could be included if previously pretreated with anti PD1/PDL1 therapy) n.b:
• a patient treated with oxaliplatin in a neoadjuvant/adjuvant situation with a recurrence of the disease within 6 months following the last administration is considered resistant to oxaliplatin and validates the criterion if no administration of oxaliplatin has been carried out in a metastatic disease situation.
• exception for VEGF if medically contraindicated during previous metastatic disease treatment (should be clearly documented in the disease history of the patient) it is allowed to included the patient with or without Bevacizumab.
• Have a performance status of 0 or 1 according to the WHO Easter Cooperative Oncology Group (ECOG)
• Knowledge of RAS, BRAF, Microsatellite status
• Baseline tumoral evaluation (thoraco-abdomino-pelvic computed tomography) perfromed within 21 days before randomization with at least one measurable lesion according to RECIST 1.1 criteria.
• Patient willing and able to comply with protocol for the duration of the study including: scheduled visits and exams, visits during the follow-up and treatment compliance.
• Adequat hepatic, renal and bone marrow function within the following limits:
• Total bilirubin ≤ 1,5 times the upper limit of normal (ULN) (unless documented Gilbert's syndrome);
• ASAT et ALAT ≤ 5 times ULN;
• Measured Creatinine clearance (Cockcroft and Gault) \> 30 ml / min
• Absolute Neutrophil Count (ANC) \> 1,5. 109 / L;
• Platelet count ≥ 150. 109 / L;

You may not qualify if:

• Other concurrent malignancies the last 3 years, except adequately treated cone-biopsied in situ carcinoma (as per exemple of the cervix, basal cell, squamous cell carcinoma of the skin, low risk prostate cancer or other insitu carcinoma juged eligible according the coordinator). Patient who have had potentially curative therapy for a prior malignancy are eligible provided there has been no evidence of disease for ≥ 3 years and the risk of recurrence is considered low.
• Symptomatic brain metastases
• Estimated prognosis \<3 months.
• Mutational status BRAF mutant (V600E only)
• Participation in progress, or in the 30 days preceding the first scheduled day of dosing in this study, in another therapeutic trial with an experimental molecule or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer.
• Severe unbalanced illness, underlying infection that may prevent the patient from receiving treatment. Patients with a clinically important and unresolved Grade 3 or 4 non-haematologic adverse reaction related to previous therapies. Also participant with any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
• Bowel obstruction or sub-obstruction or a history of inflammatory bowel disease or significant gasto intestinal disorder
• History of autoimmune or inflammatory disease or interstitial lung disease.
• Patient with congenital galactosemia, total lactase deficiency (lactose intolerance) or glucose-galactose malabsorption syndrome
• Severe arterial thromboembolic events less than 6 months before randomization
• New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg)
• Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration.
• Contraindication to receive a treatment with trifluridine/tipiracil or an anti-IL-1α (XB2001 True Human antibody) and/or patient already treated by trifluridine/tipiracil, or an anti-IL-1α.
• Concomitant systemic treatment with immunotherapy, immunosuppressants, corticosteroid therapy ≥ 10 mg equivalent prednisone/prednisolone or hormone therapy: corticosteroid therapy administered chronically, immunosuppressive treatment, biotherapy administered as part of the management of an inflammatory disease (anti-TNF, anti-IL6, anti-IL1, anti PD-1, anti EGFR etc.) and live virus vaccines administered up to 14 days prior the first scheduled dose of treatement administration.
• Current pregnancy (mandatory pregnancy test at baseline for female of childbearing potential) or breastfeeding.

Sponsors & Collaborators

• Centre Georges Francois Leclerc: lead

Study Sites (14)

Centre Georges-François Leclerc

Dijon, Bourgogne-Franche-Comté, 21000, France

Location

CHU Dijon

Dijon, Bourgogne-Franche-Comté, 21000, France

Location

ICO Angers

Angers, 49055, France

Location

Institut Sainte Catherine

Avignon, 84000, France

Location

CHU Jean Minjoz

Besançon, 25000, France

Location

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Hospitalier Carcassonne

Carcassonne, 11810, France

Location

CHU Estaing

Clermont-Ferrand, 63003, France

Location

Hopital Franco-Britannique

Levallois-Perret, 92300, France

Location

CHU Dupuytren

Limoges, 87000, France

Location

CHU Nantes

Nantes, 44000, France

Location

Cario-Hpca

Plérin, 22190, France

Location

Institut Jean Godinot

Reims, 51100, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44805, France

Location

Related Publications (1)

• Fumet JD, Roussot N, Bertaut A, Limagne E, Thibaudin M, Hervieu A, Zanetta S, Borg C, Senellart H, Pernot S, Thuillier F, Carnot A, Mineur L, Chibaudel B, Touchefeu Y, Martin-Babau J, Jary M, Labourey JL, Rederstorff E, Lepage C, Ghiringhelli F. Phase I/II study of trifluridine/tipiracil plus XB2001 versus trifluridine/tipiracil in metastatic colorectal cancer. Future Oncol. 2024;20(38):3077-3085. doi: 10.1080/14796694.2024.2415280. Epub 2024 Nov 12.

  PMID: 39530624 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Trifluridine; tipiracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2021
• First Posted: January 21, 2022
• Study Start: October 13, 2022
• Primary Completion (Estimated): October 13, 2026
• Study Completion (Estimated): October 13, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (14)