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Metastatic Colorectal CancerPhase 1NCT02848443

Study of S 95005 in Combination With Oxaliplatin in Metastatic Colorectal Cancer

A Phase 1 study testing Trifluridine/tipiracil hydrochloride (S 95005), Oxaliplatin and Bevacizumab in people with Metastatic Colorectal Cancer, run by Institut de Recherches Internationales Servier at 24 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The main purpose of this study is to assess the safety and tolerability and to determine the recommended phase 2 dose of S 95005 given in combination with oxaliplatin in patients with metastatic colorectal cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Trifluridine/tipiracil hydrochloride (S 95005), Oxaliplatin and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
24 sitesin 7 countries
Study dates
May 2016to 9 Apr 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 years or older.
  • Histologically confirmed metastatic colorectal cancer pretreated by at least one line of standard chemotherapy.
  • Restaging scan within 28 days before the first study drug intake.
  • During the dose-escalation part, patient must have at least one evaluable or measurable metastatic lesion; and during the expansion part, patient must have at least one measurable metastatic lesion.
  • Life expectancy of more than 3 months.
  • Performance status Eastern Cooperative Oncology Group (ECOG): 0-1.
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  • Adequate bone marrow, liver, and kidney function.
  • For patients who will receive bevacizumab: coagulation parameters in normal limit or in therapeutic limit for patients treated with anticoagulant.
  • For patients who will receive nivolumab: patients eligible for tumour biopsy and who agree to have two sequential biopsies during the study.
  • Women of childbearing potential must have a negative pregnancy test. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective birth control method. Women and female partners using hormonal contraceptive must also use a barrier method.
  • Capacity to take oral tablet(s) without difficulty.
  • Has provided written informed consent.
  • Is willing and able to comply with scheduled visits and study procedures.

Who cannot join

  • Grade 2 or higher peripheral neuropathy.
  • During expansion part, patients who had recurrence during or within 6 months of completion of the adjuvant chemotherapy with oxaliplatin.
  • Patients with brain metastases or leptomeningeal metastasis.
  • Other malignancy within the last 3 years (except for basal cell carcinoma or a non-invasive/in situ cervical cancer)
  • Has had certain other recent treatment e.g. major surgery, field radiation, participation in another interventional study, within the specified time frames prior to study drug administration.
  • Certain serious illnesses or serious medical conditions
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  • For patients who will receive bevacizumab: history of allergic reactions/hypersensitivity to bevacizumab, to any components used in the formulation, to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.
  • Grade 3 or higher hypersensitivity reaction to oxaliplatin or garde 1-2 hypersensitivity reaction to oxaliplatin not controlled with premedication.
  • Patient previously treated by S 95005 or history of allergic reactions attributed to compounds of similar composition to S 95005 or any of its excipient. Patient with hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
  • Any condition that, in the judgment of the Investigator, may affect the patient's ability to understand and sign the informed consent and fully comply with all study procedure.
  • Pregnancy or breast feeding.
  • For patients planned to receive nivolumab:
  • Patients with active autoimmune disease or history of clinically severe autoimmune disease.
  • Patients with a condition requiring systemic treatment with either corticosteroids (> 20 mg daily prednisone equivalent) or other immunosuppressive medications within the specified time frames prior to first study drug intake.
  • Prior treatment with anti-PD-1, anti-PD-L1, anti-programmed cell death ligand-2, anti-CD137, anti-OX-40, anti-CD40, anti-cytotoxic T lymphocyte-associated antigen-4 antibodies (CTLA-4), or any other immune checkpoint inhibitors.
  • Prior events of immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis and renal dysfunction, immune-mediated rash, immune-mediated encephalitis.
  • Allergic reactions/hypersensitivity to nivolumab or any components used in its formulation or previous severe hypersensitivity reaction to treatment with another monoclonal antibody.
  • Has a known history of active tuberculosis (Bacillus Tuberculosis).

Trial locations and contacts

24 sites in 7 countries.

24 sites in 7 countries

Spain6 sites

  • ICO Badalona. H. Germans Trials y Pujol - Servicio de Oncología médica

    Badalona, 08916

  • H. Valle de Hebrón - Servicio de Oncología - (VHIR)

    Barcelona, 08035

  • Hospital Unviersitario Gregorio Marañon - Servicio de Oncología Médica

    Madrid, 28007

  • H. Univ. Ramon y Cajal - Servicio de Oncología Medica

    Madrid, 28034

  • H. Uni. Madrid Sanchinarro - CIOCC Servicio de Oncología

    Madrid, 28050

  • H. Clinico de Valencia INCLIVA - Departamento de Hematologia y Oncologia Medica 8ª planta

    Valencia, 46010

Other trials in Spain

France5 sites

  • CHU de la Timone Hépato-Gastro-Entérologie - Oncology Digestive

    Marseille, 13005

  • Hôpital Saint-Antoine Service d'Oncologie Médicale

    Paris, 75012

  • La Pitié Salpêtrière Centre Investigation clinique Paris Est

    Paris, 75013

  • Centre Eugène Marquis Service d'Oncologie Médicale

    Rennes, 35042

  • Institut Gustave Roussy DITEP

    Villejuif, 94805

Other trials in France

Germany5 sites

  • St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum Abteilung für Hämatologie und Onkologie

    Bochum, 44791

  • Universitätsklinikum Hamburg-Eppendorf II. Medizin. Klinik und Poliklinik (Onkologie, Hämatologie)

    Hamburg, 20246

  • Klinikum der Universität München Campus Großhadern, Medizinische Klinik und Poliklinik III

    München, 81377

  • Universitätsklinikum Ulm Zentrum für Innere Medizin, Klinik für Innere Medizin I

    Ulm, 89081

  • Klinikum Wolfsburg Medizinische Klinik II

    Wolfsburg, 38440

Other trials in Germany

Hungary3 sites

  • Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly

    Budapest, 1062

  • Semmelweis Egyetem I. sz. Belgyogyaszati Klinika - Klin. Farmakologiai Reszleg

    Budapest, 1083

  • Orszagos Onkologiai Intezet "B" Belgyogyaszati-Onkologiai O. Es Klin. Farmakologiai O.

    Budapest, 1122

Other trials in Hungary

Italy3 sites

  • ARNAS - Azienda Ospedaliera Garibaldi - Nesima Struttura Complessa di Oncologia Medica

    Catania, 95122

  • Ist.Scientifico Romagnolo per lo Studio e la Cura dei Tumori Department of Clinical Oncology

    Meldola, 47014

  • Policlinico G.B. Rossi A.O.U.I. di Verona U.O.C. di Oncologia

    Verona, 37134

Other trials in Italy

Austria1 site

  • Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie

    Vienna, 1090

Other trials in Austria

United Kingdom1 site

  • Christie Hospital NHS Foundation Trust GI & Endocrine

    Manchester, M20 4BX

Other trials in United Kingdom

About this study

Official title: Phase I Dose-escalation of S 95005 (TAS-102) in Combination With Oxaliplatin in Metastatic Colorectal Cancer

The main purpose of this study is to assess the safety and tolerability and to determine the recommended phase 2 dose of S 95005 given in combination with oxaliplatin in patients with metastatic colorectal cancer.

Read the detailed description

This is a one-arm study, which will be conducted in 2 parts:

  • A dose-escalation part to determine the Maximum Tolerated Dose (MTD) of S 95005 in combination with oxaliplatin.
  • An expansion part in patients treated at the recommended dose defined in the dose escalation part of this study to evaluate the safety, PK, and preliminary efficacy of S 95005 in combination with oxaliplatin and either bevacizumab or nivolumab.
Being tested
Trifluridine/tipiracil hydrochloride (S 95005), Oxaliplatin, Bevacizumab, Nivolumab
Keywords
metastatic, colorectal, cancer, oxaliplatin, dose-escalation, Lonsurf, nivolumab, bevacizumab
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trifluridine/tipiracil hydrochloride (S 95005)Drug

    Film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride, given orally at the dose of 25 or 30 or 35 mg/m2/dose, until unacceptable toxicity according to the investigator, disease progression or patient withdrawal.

  • OxaliplatinDrug

    Concentrate for solution for infusion containing 5mg/ml of oxaliplatin, administered intravenously at the dose of 65 to 85 mg/m2, until unacceptable toxicity according to the investigator, disease progression or patient withdrawal.

  • BevacizumabDrug

    Concentrate for solution for infusion containing 25mg/ml of bevacizumab, administered intravenously at the dose of 5 mg/kg, until unacceptable toxicity according to the investigator, disease progression or patient withdrawal.

  • NivolumabDrug

    Concentrate for solution for infusion containing 10mg/ml of nivolumab, administered intravenously at the dose of 3 mg/kg, until unacceptable toxicity according to the investigator, disease progression or patient withdrawal.

Study groups in NCT02848443
Study groupRoleWhat they receive
S 95005 + oxaliplatin (+/- bevacizumab or nivolumab)ExperimentalNot described
Receives: Drug: Trifluridine/tipiracil hydrochloride (S 95005); Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of S95005 when given in combination with oxaliplatin

    Measured: up to 4 weeks after the first treatment administration

  2. Dose Limiting Toxicity (DLT) of S95005 when given in combination with oxaliplatin

    Measured: up to 4 weeks after the first treatment administration

  3. Number of participants with adverse events as a measure of safety and tolerability for S95005-oxaliplatin.

    Adverse event reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03

    Measured: through study completion, an average of 9 months

  4. Changes in standard hematology as a measure of safety and tolerability for S95005-oxaliplatin

    Measured: through study completion, an average of 9 months

  5. Changes in biochemistry as a measure of safety and tolerability for S95005-oxaliplatin

    Measured: through study completion, an average of 9 months

  6. Changes in coagulation as a measure of safety and tolerability for S95005-oxaliplatin

    Measured: through study completion, an average of 9 months

  7. Changes in urinalysis as a measure of safety and tolerability for S95005-oxaliplatin

    Measured: through study completion, an average of 9 months

  8. Changes in vital signs as a measure of safety for S95005-oxaliplatin

    Vital sign measurements will include temperature, systolic and diastolic blood pressure, heart rate, and respiratory rate.

    Measured: through study completion, an average of 9 months

  9. Changes in ECOG (Eastern Cooperative Oncology Group) performance status as a measure of safety and tolerability for S95005-oxaliplatin

    Measured: through study completion, an average of 9 months

Secondary outcomes (9)

  1. Antitumor activity assessed by RECIST (Response Evaluation Criteria in Solid Tumors) and CEA (Carcinoembryonic Antigen)

    Measured: through study completion, an average of 9 months

  2. Number of participants with adverse events as a measure of safety and tolerability for S95005-oxaliplatin + bevacizumab or nivolumab.

    Adverse event reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03

    Measured: through study completion, an average of 9 months

  3. Changes in standard hematology as a measure of safety and tolerability for S95005-oxaliplatin + bevacizumab or nivolumab.

    Measured: through study completion, an average of 9 months

  4. Changes in biochemistry as a measure of safety and tolerability for S95005-oxaliplatin + bevacizumab or nivolumab.

    Measured: through study completion, an average of 9 months

  5. Changes in coagulation as a measure of safety and tolerability for S95005-oxaliplatin + bevacizumab.

    Measured: through study completion, an average of 9 months

  6. Changes in urinalysis as a measure of safety and tolerability for S95005-oxaliplatin + bevacizumab or nivolumab.

    Measured: through study completion, an average of 9 months

  7. Changes in vital signs as a measure of safety for S95005-oxaliplatin + bevacizumab or nivolumab.

    Vital sign measurements will include temperature, systolic and diastolic blood pressure, heart rate, and respiratory rate.

    Measured: through study completion, an average of 9 months

  8. Changes in ECOG (Eastern Cooperative Oncology Group) performance status as a measure of safety and tolerability for S95005-oxaliplatin + bevacizumab or nivolumab.

    Measured: through study completion, an average of 9 months

  9. PDL-1 expression, tumour-infiltrating CD8 T cell density, for S95005-oxaliplatin + nivolumab

    Tumour biopsy at baseline and at the end of Cycle 4

    Measured: up to 8 weeks after the first treatment administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2016 (estimated)
  2. Study startMay 2016
  3. Primary completion1 Aug 2019
  4. Study completion9 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02848443
Sponsor's protocol ID
CL1-95005-001
Other IDs
2015-004894-34, 2015
Status last verified
Jul 2024
First submitted
24 Feb 2016
Last updated
25 Jul 2024
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Publications

  • Bordonaro R, Calvo A, Auriemma A, Hollebecque A, Rubovszky G, Saunders MP, Papai Z, Prager G, Stein A, Andre T, Argiles G, Cubillo A, Dahan L, Edeline J, Leger C, Cattan V, Fougeray R, Amellal N, Tabernero J. Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study. ESMO Open. 2021 Oct;6(5):100270. doi: 10.1016/j.esmoop.2021.100270. Epub 2021 Sep 20.

    PubMed 34547581

  • Argiles G, Andre T, Hollebecque A, Calvo A, Dahan L, Cervantes A, Leger C, Amellal N, Fougeray R, Tabernero J. Phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin in patients with metastatic colorectal cancer. Eur J Cancer. 2019 May;112:12-19. doi: 10.1016/j.ejca.2019.01.101. Epub 2019 Mar 16.

    PubMed 30889492

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Trifluridine/tipiracil hydrochloride (S 95005), Oxaliplatin and Bevacizumab in people with Metastatic Colorectal Cancer, run by Institut de Recherches Internationales Servier at 24 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Spain, France, Germany, Hungary, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of S95005 when given in combination with oxaliplatin (time frame: up to 4 weeks after the first treatment administration). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02848443, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.

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