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 (TASKIN)

February 12, 2024 updated by: Centre Georges Francois Leclerc

Multicentric Randomized Phase I/II Study to Evaluate Efficacy of Trifluridine/Tipiracil Plus XB2001 (Anti-IL-1α True Human Antibody) Versus Trifluridine/Tipiracil Plus Placebo in Metastatic Colorectal Cancer Patients After Failure of Oxaliplatin, Irinotecan, Fluoropyrimidine

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This project proposes to evaluate trifluridine/tipiracil plus XB2001 in patients with metastatic colorectal cancer previously treated with oxaliplatin, fluoropyrimidine and irinotecan in combination or not with an anti-angiogenic and an anti-EGFR for RAS Wild type tumor.

The project will consist of a randomized (1:1 ratio), double-blind, non-comparative, multi-center Phase II study with two treatment arms:

  • Experimental arm: trifluridine/tipiracil + XB2001
  • Control arm: trifluridine/tipiracil + placebo

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2
  • Phase 1

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
      • Angers, France, 49055
      • Avignon, France, 84000
        • Not yet recruiting
        • Institut Sainte Catherine
        • Contact:
      • Besançon, France, 25000
        • Not yet recruiting
        • CHU Jean Minjoz
        • Contact:
      • Bordeaux, France, 33000
        • Not yet recruiting
        • Institut Bergonie
        • Contact:
      • Carcassonne, France, 11810
      • Clermont-Ferrand, France, 63003
      • Levallois-Perret, France, 92300
        • Not yet recruiting
        • Hopital Franco-Britannique
        • Contact:
      • Limoges, France, 87000
      • Nantes, France, 44000
      • Plérin, France, 22190
        • Not yet recruiting
        • Cario-Hpca
        • Contact:
      • Reims, France, 51100
      • Saint Herblain, France, 44805
    • Bourgogne
      • Dijon, Bourgogne, France, 21000
      • Dijon, Bourgogne, France, 21000
        • Recruiting
        • Centre Georges-Francois Leclerc
        • Contact:
        • Contact:

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)
  • 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;
  • Haemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused)
  • Albuminemia ≥ 30 g / L;
  • Negative Hepatitis B, C and HIV serologies, or absence of active B or C hepatitis
  • Urea protein, urine dipstick should be less than 2 crossese or <1g/kg
  • Availability of tumor material dated less than 2 years with sufficient quantity (15 to 20 whithe slides)
  • Patient must be affiliated to a social health insurance
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients (urine within 72h or serum pregnancy within 14 days prior to inclusion).
  • Women of childbearing potential willing to use adequate contraception method (including the use of a mechanical method of contraception in the event of hormonal contraceptive treatment) during the treatment period and 6 months following the end of treatment.
  • Male patients with a partner of childbearing potential should use effective contraception during treatment and for up to 6 months after stopping treatment.
  • Normal ECG or ECG without clinically significant findings with QTc < 470 ms.

Exclusion Criteria:

  • Other concurrent malignancies the last 3 years, except adequately treated cone-biopsied in situ carcinoma of the cervix, basal cell, squamous cell carcinoma of the skin or low risk prostate cancer. Patient who have had potentially curative therapy for a prior malignancy are eligible provided there has been no evidence of disease for ≥ 5 years and the risk of recurrence is considered low.
  • Symptomatic brain metastases
  • Estimated prognosis <3 months.
  • Mutational status BRAF mutant
  • 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)
  • 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.
  • Patient with any psychiatric, psychological, sociological, geographical problem or other severe concomitant disease, disorder or condition that potentially compromising the understanding of the information, the safety of the patient, the interpretation of study results or the conduct of the study compliance with the study protocol and follow-up schedule.
  • Patient deprived of their liberty or under guardianship, curatorship or safeguard of justice.
  • Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution. Presence or suspicion of active bacterial, fungal or viral infections, or uncontrolled fever.
  • Major surgery within 2 weeks prior to randomization or have an unhealed operation wounds.

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: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental arm
trifluridine/tipiracil + XB2001
Drug: trifluridine/tipiracil + XB2001
trifluridine/tipiracil every 28 days + XB2001 1000mg intravenous infusion every 2 weeks
Placebo Comparator: Control arm
trifluridine/tipiracil + placebo
Drug: trifluridine/tipiracil + placebo
trifluridine/tipiracil every 28 days + Placebo intravenous infusion every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Tolerated Dose (MTD) of XB2001
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
At the end of Cycle 1 (each cycle is 28 days)
Overall survival
Time Frame: 6-month
6-month

Collaborators and Investigators

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

Sponsor

Centre Georges Francois Leclerc

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)

October 13, 2022

Primary Completion (Estimated)

October 13, 2026

Study Completion (Estimated)

October 13, 2026

Study Registration Dates

First Submitted

December 28, 2021

First Submitted That Met QC Criteria

January 15, 2022

First Posted (Actual)

January 21, 2022

Study Record Updates

Last Update Posted (Actual)

February 14, 2024

Last Update Submitted That Met QC Criteria

February 12, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-004601-31

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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