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

NCT ID: NCT02848443

Last Updated: 2024-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2020-04-09

Brief 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.

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

S 95005 + oxaliplatin (+/- bevacizumab or nivolumab)

Group Type: EXPERIMENTAL

Trifluridine/tipiracil hydrochloride (S 95005)

Intervention Type: 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.

Oxaliplatin

Intervention Type: DRUG

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.

Bevacizumab

Intervention Type: DRUG

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.

Nivolumab

Intervention Type: DRUG

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.

Interventions

Trifluridine/tipiracil hydrochloride (S 95005)

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.

Intervention Type: DRUG

Oxaliplatin

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.

Intervention Type: DRUG

Bevacizumab

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.

Intervention Type: DRUG

Nivolumab

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• 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.

Exclusion Criteria

• 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
• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Josef Tabernero, Prof

Role: PRINCIPAL_INVESTIGATOR

Vall d'Hebron University Hospital, Institute of Oncology (VHIO)

Locations

Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie

Vienna, , Austria

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

Marseille, , France

Hôpital Saint-Antoine Service d'Oncologie Médicale

Paris, , France

La Pitié Salpêtrière Centre Investigation clinique Paris Est

Paris, , France

Centre Eugène Marquis Service d'Oncologie Médicale

Rennes, , France

Institut Gustave Roussy DITEP

Villejuif, , France

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

Bochum, , Germany

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

Hamburg, , Germany

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

München, , Germany

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

Ulm, , Germany

Klinikum Wolfsburg Medizinische Klinik II

Wolfsburg, , Germany

Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly

Budapest, , Hungary

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

Budapest, , Hungary

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

Budapest, , Hungary

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

Catania, , Italy

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

Meldola, , Italy

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

Verona, , Italy

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

Badalona, , Spain

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

Barcelona, , Spain

Hospital Unviersitario Gregorio Marañon - Servicio de Oncología Médica

Madrid, , Spain

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

Madrid, , Spain

H. Uni. Madrid Sanchinarro - CIOCC Servicio de Oncología

Madrid, , Spain

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

Valencia, , Spain

Christie Hospital NHS Foundation Trust GI & Endocrine

Manchester, , United Kingdom

Countries

Austria; France; Germany; Hungary; Italy; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 34547581 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30889492 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: study-level clinical trial data

View Document

Other Identifiers

2015-004894-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL1-95005-001

Identifier Type: -

Identifier Source: org_study_id