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

NCT02848443 | Completed Phase 1

• 2 other identifiers: CL1-95005-0012015-004894-34
• Study Type: interventional
• Target: 78
• Locations: 7 countries
• Sites: 24

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.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic; colorectal; cancer; oxaliplatin; dose-escalation; Lonsurf; nivolumab; bevacizumab

Outcome Measures

Primary Outcomes (9)

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

  up to 4 weeks after the first treatment administration

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

  up to 4 weeks after the first treatment administration

• 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

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

• 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.

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

Secondary Outcomes (9)

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

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

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

  through study completion, an average of 9 months

Other Outcomes (4)

• Circulating protein biomarkers analysis

  through study completion, an average of 9 months

• Circulating tumour DNA analysis

  day 1 of cycle 1 (each cycle is 28 days)

• Circulating protein biomarkers in relation to ICD (immune cell death)

  through study completion, an average of 9 months

Study Arms (1)

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

EXPERIMENTAL

Drug: Trifluridine/tipiracil hydrochloride (S 95005); Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Nivolumab

Interventions

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.

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

Oxaliplatin 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.

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

Bevacizumab 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.

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

Nivolumab 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.

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

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead
• ADIR, a Servier Group company: collaborator

Study Sites (24)

Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie

Vienna, 1090, Austria

Location

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

Marseille, 13005, France

Location

Hôpital Saint-Antoine Service d'Oncologie Médicale

Paris, 75012, France

Location

La Pitié Salpêtrière Centre Investigation clinique Paris Est

Paris, 75013, France

Location

Centre Eugène Marquis Service d'Oncologie Médicale

Rennes, 35042, France

Location

Institut Gustave Roussy DITEP

Villejuif, 94805, France

Location

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

Bochum, 44791, Germany

Location

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

Hamburg, 20246, Germany

Location

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

München, 81377, Germany

Location

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

Ulm, 89081, Germany

Location

Klinikum Wolfsburg Medizinische Klinik II

Wolfsburg, 38440, Germany

Location

Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly

Budapest, 1062, Hungary

Location

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

Budapest, 1083, Hungary

Location

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

Budapest, 1122, Hungary

Location

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

Catania, 95122, Italy

Location

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

Meldola, 47014, Italy

Location

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

Verona, 37134, Italy

Location

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

Badalona, 08916, Spain

Location

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

Barcelona, 08035, Spain

Location

Hospital Unviersitario Gregorio Marañon - Servicio de Oncología Médica

Madrid, 28007, Spain

Location

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

Madrid, 28034, Spain

Location

H. Uni. Madrid Sanchinarro - CIOCC Servicio de Oncología

Madrid, 28050, Spain

Location

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

Valencia, 46010, Spain

Location

Christie Hospital NHS Foundation Trust GI & Endocrine

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 34547581 BACKGROUND

• 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.

  PMID: 30889492 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

Trifluridine; Oxaliplatin; Bevacizumab; Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Josef Tabernero, Prof

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

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: July 28, 2016
• Study Start: May 1, 2016
• Primary Completion: August 1, 2019
• Study Completion: April 9, 2020
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

FR (5); AU (1); DE (5); HU (3); ES (6); GB (1); IT (3)