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Colo-rectal CancerPhase 3AGENTNCT03750786

A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer

A Phase 3 study testing Arfolitixorin and Leucovorin in people with Colo-rectal Cancer, run by Isofol Medical AB at 94 sites in 10 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

This is a multicenter, randomized, parallel-group, Phase III study in at least 440 patients with advanced colorectal cancer to compare the efficacy of treatment with arfolitixorin versus Leucovorin in combination with 5-fluorouracil, oxaliplatin, and bevacizumab according to modified FOLFOX-6 until PD according to… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colo-rectal Cancer
What is being tested?
Arfolitixorin and Leucovorin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
490 participants
Where
94 sitesin 10 countries
Study dates
18 Dec 2018to 18 Nov 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Colorectal adenocarcinoma verified by biopsy.
  • Availability of biopsy material, from the primary tumor or metastasis, allowing for analysis of tumor gene expression.
  • Non-resectable metastatic CRC planned for first line therapy with 5-FU, Leucovorin, oxaliplatin, and bevacizumab.
  • Evaluable disease with at least one measurable lesion of metastatic disease (≥10 mm in longest diameter on axial image on CT-scan or alternatively MRI with <5 mm reconstruction interval) or lymph node (≥ 15 mm in shortest axis when assessed by CT) obtained within 28 days of randomization.
  • Life expectancy of more than 4 months.
  • ECOG performance status 0 or 1.
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  • Hemoglobin (Hb) > 80 g/L, Absolute neutrophil count (ANC) > 1.5x10E9/L. Thrombocytes > 100x10E9/L.
  • Creatinine clearance > 50 mL/min, Total bilirubin < 1.5 x ULN, AST and ALT < 3 x ULN (and < 5 x ULN in case of liver metastases).
  • Male or female ≥18 years of age.
  • Female patients of childbearing potential must have a negative urine pregnancy test and use adequate contraceptive measures . Male patients must use adequate contraceptive measures .
  • Voluntarily signed informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Who cannot join

  • Malignant tumors other than colorectal adenocarcinomas (current or within the previous five years), with the exception for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix.
  • Less than 6 months between randomization and completion of the last anti-cancer treatment (chemotherapy/radiotherapy/immunotherapy, etc.). (NB: Rectal cancer treatment shorter than 8 weeks of chemo/radiation therapy is allowed.)
  • Confirmation of progressive disease within 6 months after completion of prior adjuvant anti-cancer treatment.
  • Indication for any metastatic Colo-rectal Cancer (mCRC) surgery or anti-cancer treatment other than study treatment.
  • Prior treatment with arfolitixorin.
  • Indication for treatment with a 5-FU analogue, or 5-FU for a condition other than mCRC.
Show all 20Show fewer
  • Known Dihydropyrimidine Dehydrogenase Deficiency (DPD) deficiency.
  • Known or suspected central nervous system (CNS) metastases.
  • Unresolved bowel obstruction, uncontrolled Crohn's disease, or ulcerative colitis.
  • History of cardiac disease with a New York Heart Association Class II or greater, congestive heart failure, myocardial infarction, or unstable angina at any time during the 6 months prior to randomization, or serious arrhythmias requiring medication for treatment.
  • Current CTCAE ≥ grade 3 diarrhea.
  • Current chronic infection or uncontrolled serious illness causing immunodeficiency.
  • Known or suspected hypersensitivity or intolerance to arfolitixorin, LV, 5-FU, oxaliplatin, or bevacizumab.
  • Breastfeeding patients.
  • Patient who received investigational drugs in other clinical trials within 28 days, or 5 half-lives of the investigational drug, prior to randomization.
  • Patient with serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Ongoing drug or alcohol abuse, as deemed by the Investigator.
  • Any condition that, in the opinion of the Investigator, could compromise the patient's safety or adherence to the study protocol.
  • Involvement, or related to people involved in the planning or conduct of the study (applies to both Isofol Medical AB (publ) staff and staff at the study site)
  • Surgery (excluding previous diagnostic biopsy) in the 28-day period before randomization

Trial locations and contacts

94 sites in 10 countries.

94 sites in 10 countries

United States18 sites

  • 840-14 - University of Michigan Cancer Center

    Ann Arbor, Michigan, 48109

  • 840-29 - Ashland-Bellefonte Cancer Center

    Ashland, Kentucky, 41101

  • 840-04 - St. Vincent Frontier Cancer Center

    Billings, Montana, 59102

  • 840-27 - Charleston Hematology Oncology Associates

    Charleston, South Carolina, 29414

  • 840-13 - UCH-MHS d/b/a Memorial Health System

    Colorado Springs, Colorado, 80909

  • 840-24 - Banner Gateway Medical Center

    Gilbert, Arizona, 85234

  • 840-34 - Banner MD Anderson Cancer Center

    Greeley, Colorado, 80631

  • 840-30 - Joliet Oncology-Hematology Associates

    Joliet, Illinois, 60435

  • 840-15 - University of Southern California

    Los Angeles, California, 91001

  • 840-19 - University of Louisville Research Foundation Inc. (ULRF)

    Louisville, Kentucky, 40202-1798

  • 840-32 - University of Miami

    Miami, Florida, 33136

  • 840-12 - Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • 840-01 - HOAG Memorial Hospital

    Newport Beach, California, 92663

  • 840-22 - University of Oklahoma Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • 840-10 - Oregon Health and Science University-Knight Cancer Institute

    Portland, Oregon, 97239

  • 840-02 - The University of Texas Health Science Center

    San Antonio, Texas, 78229

  • 840-08 - Pinellas Hematology Oncology

    St. Petersburg, Florida, 33709

  • 840-06 - Cancer Center of Kansas

    Wichita, Kansas, 67214

Other trials in United States

Japan15 sites

  • 392-10 - Aichi Cancer Center

    Aichi, 464-8681

  • 392-01 - National Cancer Center Hospital East

    Chiba, 277-8577

  • 392-09 - National Hospital Organization Shikoku Cancer Center

    Ehime, 791-0280

  • 392-07 - Gifu University Hospital

    Gifu, 501-1194

  • 392-12 - Saitama Medical University International Medical Center

    Hidaka, 350-1298

  • 392-05 - University of Tsukuba Hospital

    Ibaraki, 305-8576

  • 392-15 - Kagawa University Hospital

    Kagawa, 761-0793

  • 392-08 - St.Marianna University School of Medicine Hospital

    Kanagawa, 216-8511

  • 392-11 - National Hospital Organization Osaka National Hospital

    Osaka, 540-0006

  • 392-13 - Osaka General Medical Center

    Osaka, 558-8558

  • 392-14 - Kansai Medical University Hospital

    Osaka, 573-1191

  • 392-04 - Saitama Cancer Center

    Saitama, 362-0806

  • 392-03 - Hokkaido University Hospital

    Sapporo Hokkaido, 060-8648

  • 392-02 - Shizuoka Cancer Center

    Shizuoka, 411-8777

  • 392-06 - National Cancer Center Hospital

    Tokyo, 104-0045

Other trials in Japan

Germany12 sites

  • 276-12 - Charité - Universitätsmedizin Berlin

    Berlin, 10117

  • 276-02 - Universitätsklinikum Carl Gustav Carus

    Dresden, 01307

  • 276-03 - Krankenhaus Nordwest GmbH

    Frankfurt am Main, 60488

  • 276-10 - Universitärers Cancer Center Hamburg (UCCH)

    Hamburg, 20246

  • 276-11 - Klinikum Kassel GmbH

    Kassel, 34125

  • 276-04 - MVZ Mitte - Onkologische Schwerpunktpraxis

    Leipzig, 04103

  • 276-13 - Universitäres Krebszentrum Leipzig (UCCL)

    Leipzig, 04103

  • 276-07 - Philipps-Universität Marburg

    Marburg, 35032

  • 276-08 - Carl von Basedow Klinikum Saalekrei GmbH

    Merseburg, 06217

  • 276-01 - Klinikum der Universität München - Campus Grosshadern

    München, 81377

  • 276-09 - Klinikum Nürnberg Nord

    Nuremberg, 90419

  • 276-05 - Kliniken Nordoberpfalz AG

    Weiden, 92637

Other trials in Germany

Canada10 sites

  • 124-03 - William Osler Health System - Brampton Civi Hospital

    Brampton, Ontario, L6R 3J7

  • 124-04 - CISSS de l'Outaouais - Hôpital de Gatineau

    Gatineau, Quebec, J8V 2L4

  • 124-02 - Hôpital de la Cité-de-la-Santé

    Laval, H7M 3L9

  • 124-11 - CISSS de Chaudière-Appalaches

    Lévis, Quebec, G6V 3Z1

  • 124-01 - Montreal University Health Center

    Montreal, Quebec, H4A 3J1

  • 124-08 - Hôpital Maisonneuve Rosemont

    Montreal, H1T 2M4

  • 124-06 - Jewish General Hospital

    Montreal, H3T 1E2

  • 124-05 - Ottawa Hospital Research Institute

    Ottawa, KIH8L6

  • 124-10 - Thunder Bay Regional Health Research Institute

    Thunder Bay, Ontario, P7B 6V4

  • 124-07 - Sunnybrook Research Institute

    Toronto, Ontario, M4N 3M5

Other trials in Canada

France9 sites

  • 250-07 - Hôpital Henri Mondor

    Créteil, 94010

  • 250-06 - Centre Georges Francois Leclerc

    Dijon, 21000

  • 250-01 - Institute Hospitalier Franco-Britannique

    Levallois-Perret, 92300

  • 250-09 - Hopital Privé Jean Mermoz

    Lyon, 69373

  • 250-08 - Hôpital Européen

    Marseille, 13003

  • 250-03 - Hôpital Paris Saint Joseph

    Paris, 75014

  • 250-02 - Hôpital Saint-Antoine

    Paris, 75571

  • 250-04 - Polyclinique Francheville

    Périgueux, 24000

  • 250-05 - Clinique Sainte Anne

    Strasbourg, 67000

Other trials in France

Australia8 sites

  • 036-10 - Border Medical Oncology Research Unit

    Albury, New South Wales, 2640

  • 036-04 - Peninsula Health - Frankston Hospital

    Frankston, Victoria, 3199

  • 036-01 - Western Health - Sunshine Hospital

    Melbourne, Victoria, 3021

  • 036-07 - Northern Health - Epping Hospital

    Melbourne, Victoria, 3076

  • 036-05 - Monash Health

    Melbourne, Victoria, 3168

  • 036-02 - Chris O'Brien Lifehouse

    Sydney, New South Wales, 2050

  • 036-03 - Westmead Hospital

    Sydney, New South Wales, 2145

  • 036-09 - Southern Medical Day Care Center

    Wollongong, New South Wales, 2500

Other trials in Australia

Spain8 sites

  • 724-03 - Instituto Oncologico Baselga - Hospital Quiron

    Barcelona, 08023

  • 724-07 - Hospital del la Santa Creu i Sant Pau

    Barcelona, 08026

  • 724-01 - Vall d'Hebron Institute of Oncology

    Barcelona, 08035

  • 724-06 - Hospital Universitario Reina Sofia

    Córdoba, 14004

  • 724-04 - Hospital Unviersitario 12 de Octubre

    Madrid, 28041

  • 724-09 - Hospital Universitario HM Sanchinarro

    Madrid, 28050

  • 724-02 - Hospital Regional Universitario Carlos Haya

    Málaga, 29010

  • 724-05 - Hospital Universitario Virgen del Rocío

    Seville, 41013

Other trials in Spain

Austria6 sites

  • 040-02 - Klinikum Klagenfurt am Wörthersee

    Klagenfurt, 9020

  • 040-06 - Ordensklinikum Linz GmbH - Barmherzige Schwestern

    Linz, 4010

  • 040-03 - Uniklinikum Salzburg

    Salzburg, 5020

  • 040-01 - Allgemeines Krankenhaus der Stadt Wien

    Vienna, 1090

  • 040-05 - Wilhelminenspital

    Vienna, 1160

  • 040-04 - Landesklinikum Wiener Neustadt

    Wiener Neustadt, 2700

Other trials in Austria

Greece6 sites

  • 300-04 - 251 Airforce Hospital

    Athens, 11525

  • 300-01 - Aretaieo Hospital

    Athens, 11528

  • 300-02 - University General Hospital Attikon

    Athens, 15562

  • 300-03 - Metropolitan General Hospital

    Athens, 15562

  • 300-05 - Metropolitan General SA

    Athens, 15562

  • 300-06 - University General Hospital of Larissa

    Larissa, 41110

Other trials in Greece

Sweden2 sites

  • 752-02 - Södersjukhuset

    Stockholm, 118 83

  • 752-01 - Akademiska Sjukhuset

    Uppsala, 751 85

Other trials in Sweden

About this study

Official title: A Randomized, Multicenter, Parallel-group, Phase III Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer

This is a multicenter, randomized, parallel-group, Phase III study in at least 440 patients with advanced colorectal cancer to compare the efficacy of treatment with arfolitixorin versus Leucovorin in combination with 5-fluorouracil, oxaliplatin, and bevacizumab according to modified FOLFOX-6 until PD according to RECIST 1.1 criteria.

Being tested
Arfolitixorin, Leucovorin
Medical subject headings
Colonic Neoplasms

What participants receive

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

  • ArfolitixorinDrug

    Bevacizumab 5 mg/kg intravenous infusion; Oxaliplatin 85 mg/m2 intravenous infusion; 5-FU 400 mg/m2 intravenous bolus; Arfolitixorin 60 mg/m2 intravenous bolus; 5-FU 2400 mg/m2 intravenous infusion; Arfolitixorin 60 mg/m2 intravenous bolus

  • LeucovorinDrug

    Bevacizumab 5 mg/kg intravenous infusion; Oxaliplatin 85 mg/m2 intravenous infusion; Leucovorin 400 mg/m2 intravenous infusion; 5-FU 400 mg/m2 intravenous infusion; 5-FU 2400 mg/m2 intravenous infusion

Study groups in NCT03750786
Study groupRoleWhat they receive
Group AExperimentalARFOX (Arfolitixorin and 5-FU and Oxaliplatin) and Bevacizumab
Receives: Drug: Arfolitixorin
Group BActive comparatormFOLFOX-6 (Leucovorin and 5-FU and Oxaliplatin) and Bevacizumab
Receives: Drug: Leucovorin

What is being measured

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

  1. Overall Response Rate

    Best ORR, defined as the best response recorded from the start of the study treatment until the end of treatment.

    Measured: Until disease progression, an average of ten months

Secondary outcomes (2)

  1. Progression Free Survival

    PFS, defined as the time from randomization to first occurrence of tumor progression based on CT-scans/MRIs.

    Measured: Until disease progression, an average of ten months

  2. Duration of Response

    The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented.

    Measured: Until disease progression, an average of ten months

Timeline

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

  1. First posted23 Nov 2018
  2. Study start18 Dec 2018
  3. Primary completion18 Nov 2022
  4. Study completion18 Nov 2022

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
490 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03750786
Sponsor's protocol ID
ISO-CC-007
Acronym
AGENT
Status last verified
Oct 2023
First submitted
19 Nov 2018
Last updated
26 Oct 2023
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Tabernero J, Yoshino T, Stintzing S, de Gramont A, Gibbs P, Jonker DJ, Nygren P, Papadimitriou C, Prager GW, Tell R, Lenz HJ. A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial. Cancer Res Commun. 2024 Jan 4;4(1):28-37. doi: 10.1158/2767-9764.CRC-23-0361.

    PubMed 38059497

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Arfolitixorin and Leucovorin in people with Colo-rectal Cancer, run by Isofol Medical AB at 94 sites in 10 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 11 inclusion and 20 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 26 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 94 sites in United States, Japan, Germany, Canada, France and 5 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response Rate (time frame: Until disease progression, an average of ten months). 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 NCT03750786, which also lists 1 linked publication.

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 26 Oct 2023.

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