A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer (AGENT)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03750786 |
Recruitment Status :
Recruiting
First Posted : November 23, 2018
Last Update Posted : January 15, 2021
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Colo-rectal Cancer | Drug: Arfolitixorin Drug: Leucovorin | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 440 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Single (Outcomes Assessor) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | December 18, 2018 |
Estimated Primary Completion Date : | October 31, 2021 |
Estimated Study Completion Date : | January 31, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Group A
ARFOX (Arfolitixorin and 5-FU and Oxaliplatin) and Bevacizumab
|
Drug: Arfolitixorin
Arfolitixorin and 5-FU and Oxaliplatin and Bevacizumab |
Active Comparator: Group B
mFOLFOX-6 (Leucovorin and 5-FU and Oxaliplatin) and Bevacizumab
|
Drug: Leucovorin
Leucovorin and 5-FU and Oxaliplatin and Bevacizumab |
- Overall response rate [ Time Frame: Until disease progression, an average of ten months ]Best ORR, defined as the best response recorded from the start of the study treatment until the end of treatment.
- Progression free survival [ Time Frame: Until disease progression, an average of ten months ]PFS, defined as the time from randomization to first occurrence of tumor progression based on CT-scans/MRIs.
- Duration of response [ Time Frame: Until disease progression, an average of ten months ]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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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, 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) obtained within 28 days of randomization.
- Life expectancy of more than 4 months.
- ECOG performance status 0 or 1.
- Hemoglobin (Hb) > 100 g/L, Absolute neutrophil count (ANC) > 1.5x109/L. Thrombocytes > 100x109/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.
Exclusion Criteria:
- 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/surgery, 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 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.
- 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)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03750786
Contact: Roger Tell, MD, PhD | +46 (0) 760 293 911 | roger.tell@isofolmedical.com |

United States, Arizona | |
840-24 - Banner Gateway Medical Center | Recruiting |
Gilbert, Arizona, United States, 85234 | |
Contact: Madappa Kundranda, MD | |
United States, California | |
840-33 - Cedars-Sinai | Not yet recruiting |
Los Angeles, California, United States, 90048 | |
Contact: Jun Gong, MD | |
840-01 - University of Southern California | Recruiting |
Los Angeles, California, United States, 91001 | |
Contact: Heinz-Josef Lenz, MD | |
840-15 - HOAG Memorial Hospital | Recruiting |
Newport Beach, California, United States, 92663 | |
Contact: Heinz-Josef Lenz, MD | |
United States, Colorado | |
840-13 - UCH-MHS d/b/a Memorial Health System | Recruiting |
Colorado Springs, Colorado, United States, 80909 | |
Contact: Robert Hoyer, MD | |
840-34 - Banner MD Anderson Cancer Center | Recruiting |
Greeley, Colorado, United States, 80631 | |
Contact: Benjamin George, MD | |
United States, District of Columbia | |
840-23 - Georgetown University | Withdrawn |
Washington, District of Columbia, United States, 20057 | |
United States, Florida | |
840-32 - University of Miami | Recruiting |
Miami, Florida, United States, 33136 | |
Contact: Agustin Pimentel, MD | |
840-08 - Pinellas Hematology Oncology | Recruiting |
Saint Petersburg, Florida, United States, 33709 | |
Contact: Pratibha Desai, Dr. MD | |
United States, Illinois | |
840-38 - Northwestern University Feinberg School of Medicine | Not yet recruiting |
Chicago, Illinois, United States, 60611 | |
Contact: Al Benson, MD | |
840-11 - North Shore University Health System | Withdrawn |
Evanston, Illinois, United States, 60201 | |
840-30 - Joliet Oncology-Hematology Associates | Recruiting |
Joliet, Illinois, United States, 60435 | |
Contact: Nafisa Burhani, MD | |
United States, Kansas | |
840-06 - Cancer Center of Kansas | Recruiting |
Wichita, Kansas, United States, 67214 | |
Contact: Shaker Dakhil, MD | |
United States, Kentucky | |
840-29 - Ashland-Bellefonte Cancer Center | Recruiting |
Ashland, Kentucky, United States, 41101 | |
Contact: Venu Konala, MD | |
840-19 - University of Louisville Research Foundation Inc. (ULRF) | Recruiting |
Louisville, Kentucky, United States, 40202-1798 | |
Contact: Adam Rojan, MD | |
United States, Michigan | |
840-14 - University of Michigan Cancer Center | Recruiting |
Ann Arbor, Michigan, United States, 48109 | |
Contact: John Krauss, MD | |
840-18 - Wayne State University | Withdrawn |
Detroit, Michigan, United States, 48201 | |
840-36 - Clinical Oncology Associates | Withdrawn |
Farmington Hills, Michigan, United States, 48334 | |
United States, Montana | |
840-04 - St. Vincent Frontier Cancer Center | Recruiting |
Billings, Montana, United States, 59102 | |
Contact: Patrick Cobb, MD | |
United States, New Jersey | |
840-12 - Rutgers Cancer Institute of New Jersey | Recruiting |
New Brunswick, New Jersey, United States, 08903 | |
Contact: Howard Hochster, MD | |
United States, New York | |
840-03 - Roswell Park Cancer Institute | Withdrawn |
Buffalo, New York, United States, 14263 | |
Mount Sinai-Union Square | Withdrawn |
New York, New York, United States, 10019 | |
United States, Ohio | |
Gabrail Cancer Center Research UC | Withdrawn |
Canton, Ohio, United States, 44718 | |
United States, Oklahoma | |
840-22 - University of Oklahoma Stephenson Cancer Center | Recruiting |
Oklahoma City, Oklahoma, United States, 73104 | |
Contact: Susanna Ulahannan, MD | |
United States, Oregon | |
840-10 - Oregon Health and Science University-Knight Cancer Institute | Recruiting |
Portland, Oregon, United States, 97239 | |
Contact: Adel Kardosh, MD | |
United States, Pennsylvania | |
840-28 - Asplundh Cancer Pavillon-Abington Hospital | Withdrawn |
Abington, Pennsylvania, United States, 19001 | |
840-31 - Penn State Health | Not yet recruiting |
Hershey, Pennsylvania, United States, 17033 | |
Contact: Ali A. Mohamed, MD | |
United States, South Carolina | |
840-27 - Charleston Hematology Oncology Associates | Recruiting |
Charleston, South Carolina, United States, 29414 | |
Contact: Brian Lingerfelt, MD | |
United States, Texas | |
840-39 - Harlingen Medical Center | Withdrawn |
Harlingen, Texas, United States, 78550 | |
840-02 - The University of Texas Health Science Center | Recruiting |
San Antonio, Texas, United States, 78229 | |
Contact: Sukeshi P Arora, MD | |
United States, Washington | |
840-05 - Fred Hutchinson Cancer Research Center | Recruiting |
Seattle, Washington, United States, 98109 | |
Contact: Stacey Cohen, MD | |
Australia, New South Wales | |
036-10 - Border Medical Oncology Research Unit | Recruiting |
Albury, New South Wales, Australia, 2640 | |
Contact: Craig Underhill, MD | |
036-02 - Chris O'Brien Lifehouse | Recruiting |
Sydney, New South Wales, Australia, 2050 | |
Contact: Kate Mahon, MD | |
036-03 - Westmead Hospital | Recruiting |
Sydney, New South Wales, Australia, 2145 | |
Contact: Mark Wong, MD | |
036-08 - Tweed Hospital | Recruiting |
Tweed Heads, New South Wales, Australia, 2485 | |
Contact: Ratnesh Srivastav, MD | |
036-09 - Southern Medical Day Care Center | Recruiting |
Wollongong, New South Wales, Australia, 2500 | |
Contact: Philip Clingan, MD | |
Australia, South Australia | |
036-06 - Adelaide Cancer Center | Withdrawn |
Adelaide, South Australia, Australia, 5037 | |
Australia, Victoria | |
036-04 - Peninsula Health - Frankston Hospital | Recruiting |
Frankston, Victoria, Australia, 3199 | |
Contact: Babak Tamjid, MD | |
036-01 - Western Health - Sunshine Hospital | Recruiting |
Melbourne, Victoria, Australia, 3021 | |
Contact: Peter Gibbs, MD | |
036-07 - Northern Health - Epping Hospital | Recruiting |
Melbourne, Victoria, Australia, 3076 | |
Contact: Geoff Chong, MD | |
036-05 - Monash Health | Recruiting |
Melbourne, Victoria, Australia, 3168 | |
Contact: Sophia Frentzas, MD | |
Austria | |
040-02 - Klinikum Klagenfurt am Wörthersee | Recruiting |
Klagenfurt, Austria, 9020 | |
Contact: Wolfgang Eisterer, Prof. | |
040-06 - Ordensklinikum Linz GmbH - Barmherzige Schwestern | Recruiting |
Linz, Austria, 4010 | |
Contact: Ulrich Popper, Dr. | |
040-03 - Landeskrankenhaus | Recruiting |
Salzburg, Austria, 5020 | |
Contact: Richard Greil, Prof. | |
040-04 - Landesklinikum Wiener Neustadt | Recruiting |
Wiener Neustadt, Austria, 2700 | |
Contact: Birgit Grünberger, Dr. MD | |
040-01 - Allgemeines Krankenhaus der Stadt Wien | Recruiting |
Wien, Austria, 1090 | |
Contact: Gerald Prager, MD | |
040-05 - Wilhelminenspital | Recruiting |
Wien, Austria, 1160 | |
Contact: Dora Niedersüss-Beke, MD | |
Canada, Ontario | |
124-03 - William Osler Health System - Brampton Civi Hospital | Recruiting |
Brampton, Ontario, Canada, L6R 3J7 | |
Contact: Stephen Reingold, MD | |
124-10 - Thunder Bay Regional Health Research Institute | Recruiting |
Thunder Bay, Ontario, Canada, P7B 6V4 | |
Contact: Amir Faghih, MD | |
124-07 - Sunnybrook Research Institute | Recruiting |
Toronto, Ontario, Canada, M4N 3M5 | |
Contact: Michael Raphael, MD | |
Canada, Quebec | |
124-04 - CISSS de l'Outaouais - Hôpital de Gatineau | Recruiting |
Gatineau, Quebec, Canada, J8V 2L4 | |
Contact: Dominique Fréchette, MD | |
124-11 - CISSS de Chaudière-Appalaches | Recruiting |
Lévis, Quebec, Canada, G6V 3Z1 | |
Contact: Alain Filion, MD | |
124-01 - Montreal University Health Center | Recruiting |
Montreal, Quebec, Canada, H4A 3J1 | |
Contact: Thierry Alcindor, MD | |
Canada | |
124-02 - Hôpital de la Cité-de-la-Santé | Recruiting |
Laval, Canada, H7M 3L9 | |
Contact: Nathalie Aucoin, MD | |
124-08 - Hôpital Maisonneuve Rosemont | Recruiting |
Montréal, Canada, H1T 2M4 | |
Contact: Lucas Sideris, MD | |
124-06 - Jewish General Hospital | Recruiting |
Montréal, Canada, H3T 1E2 | |
Contact: Petr Kavan, MD | |
124-05 - Ottawa Hospital Research Institute | Recruiting |
Ottawa, Canada, KIH8L6 | |
Contact: Derek Jonker, MD | |
France | |
250-07 - Hôpital Henri Mondor | Recruiting |
Créteil, France, 94010 | |
Contact: Christoph Tournigand, MD | |
250-06 - Centre Georges Francois Leclerc | Recruiting |
Dijon, France, 21000 | |
Contact: Francois Ghiringhelli, Prof. | |
250-01 - Institute Hospitalier Franco-Britannique | Recruiting |
Levallois-Perret, France, 92300 | |
Contact: Aimery de Gramont, Prof. | |
250-09 - Hopital Privé Jean Mermoz | Recruiting |
Lyon, France, 69373 | |
Contact: Jérôme Desramé, Dr. | |
250-08 - Hôpital Européen | Recruiting |
Marseille, France, 13003 | |
Contact: Yves Rinaldi, Dr. | |
250-03 - Hôpital Paris Saint Joseph | Recruiting |
Paris, France, 75014 | |
Contact: Nabil Baba Hamed, MD | |
250-02 - Hôpital Saint-Antoine | Recruiting |
Paris, France, 75571 | |
Contact: Thierry André, Prof. | |
250-04 - Polyclinique Francheville | Recruiting |
Périgueux, France, 24000 | |
Contact: Laurent Cany, MD | |
250-05 - Clinique Sainte Anne | Recruiting |
Strasbourg, France, 67000 | |
Contact: Louis-Marie Dourthe, MD | |
Germany | |
276-12 - Charité - Universitätsmedizin Berlin | Recruiting |
Berlin, Germany, 10117 | |
Contact: Sebastian Stintzing, Prof. | |
276-02 - Universitätsklinikum Carl Gustav Carus | Recruiting |
Dresden, Germany, 01307 | |
Contact: Gunnar Folprecht, PD Dr.med. | |
276-03 - Krankenhaus Nordwest GmbH | Recruiting |
Frankfurt am Main, Germany, 60488 | |
Contact: Thorsten Götze, PD Dr.med. | |
276-10 - Universitärers Cancer Center Hamburg (UCCH) | Recruiting |
Hamburg, Germany, 20246 | |
Contact: Marianne Sinn, Dr.med. | |
276-11 - Klinikum Kassel GmbH | Recruiting |
Kassel, Germany, 34125 | |
Contact: Martin Wolf, Prof. Dr. | |
276-06 - Städisches Krankenhaus Kiel | Recruiting |
Kiel, Germany, 24107 | |
Contact: Roland Repp, Prof.Dr.med. | |
276-04 - MVZ Mitte - Onkologische Schwerpunktpraxis | Recruiting |
Leipzig, Germany, 04103 | |
Contact: Albrecht Kertzschmar, Dr.med. | |
276-13 - Universitäres Krebszentrum Leipzig (UCCL) | Recruiting |
Leipzig, Germany, 04103 | |
Contact: Ulrich Hacker, Prof. Dr.med | |
276-07 - Philipps-Universität Marburg | Recruiting |
Marburg, Germany, 35032 | |
Contact: Jorge Riera, Dr.med. | |
276-08 - Carl von Basedow Klinikum Saalekrei GmbH | Recruiting |
Merseburg, Germany, 06217 | |
Contact: Jörn Rüssel, MD | |
276-01 - Klinikum der Universität München - Campus Grosshadern | Recruiting |
München, Germany, 81377 | |
Contact: Volker Heinemann, Prof.Dr.med. | |
276-09 - Klinikum Nürnberg Nord | Recruiting |
Nürnberg, Germany, 90419 | |
Contact: Gabriele Siegler, Dr.med. | |
276-05 - Kliniken Nordoberpfalz AG | Recruiting |
Weiden, Germany, 92637 | |
Contact: Frank Kullmann, Prof. Dr. | |
Greece | |
300-04 - 251 Airforce Hospital | Recruiting |
Athens, Greece, 11525 | |
Contact: Nikolaos Kentepozidis, MD | |
300-01 - Aretaieo Hospital | Recruiting |
Athens, Greece, 11528 | |
Contact: Christos Papadimitriou, Prof. | |
300-02 - University General Hospital Attikon | Recruiting |
Athens, Greece, 15562 | |
Contact: Dimitrios Boumpas, Prof. | |
300-03 - Metropolitan General Hospital | Recruiting |
Athens, Greece, 15562 | |
Contact: Panagiotis Katsaounis, MD | |
300-05 - Metropolitan General SA | Recruiting |
Athen, Greece, 15562 | |
Contact: Evangelos Bournakis, MD | |
300-06 - University General Hospital of Larissa | Recruiting |
Larissa, Greece, 41110 | |
Contact: Athanasios Kotsakis, MD | |
Japan | |
392-01 - National Cancer Center Hospital East | Recruiting |
Chiba, Japan, 277-8577 | |
Contact: Hiroya Taniguchi, MD PhD | |
392-05 - University of Tsukuba Hospital | Recruiting |
Ibaraki, Japan, 305-8576 | |
Contact: Toshikazu Moriwaki, MD | |
392-08 - St.Marianna University School of Medicine Hospital | Recruiting |
Kanagawa, Japan, 216-8511 | |
Contact: Yu Sunakawa, MD | |
392-13 - Osaka General Medical Center | Recruiting |
Osaka, Japan, 558-8558 | |
Contact: Yoshinori Kagawa, MD | |
392-14 - Kansai Medical University Hospital | Recruiting |
Osaka, Japan, 573-1191 | |
Contact: Hironaga Satake, MD | |
392-04 - Saitama Cancer Center | Recruiting |
Saitama, Japan, 362-0806 | |
Contact: Masako Asayma, MD | |
392-02 - Shizuoka Cancer Center | Recruiting |
Shizuoka, Japan, 411-8777 | |
Contact: Kentaro Yamazaki, MD PhD | |
Spain | |
724-03 - Instituto Oncologico Baselga - Hospital Quiron | Recruiting |
Barcelona, Spain, 08023 | |
Contact: José Luis Cuadra Urteaga, MD | |
724-07 - Hospital del la Santa Creu i Sant Pau | Recruiting |
Barcelona, Spain, 08026 | |
Contact: David Páez, MD PhD | |
724-01 - Vall d'Hebron Institute of Oncology | Recruiting |
Barcelona, Spain, 08035 | |
Contact: Elena Élez, MD PhD | |
724-06 - Hospital Universitario Reina Sofia | Recruiting |
Córdoba, Spain, 14004 | |
Contact: José Ortiz Morales, MD | |
724-08 - Hospital Universitario Ramón y Cajal | Withdrawn |
Madrid, Spain, 28034 | |
724-04 - Hospital Unviersitario 12 de Octubre | Recruiting |
Madrid, Spain, 28041 | |
Contact: Cristina Gravalos, MD | |
724-09 - Hospital Universitario HM Sanchinarro | Recruiting |
Madrid, Spain, 28050 | |
Contact: Antonio Cubillo, MD | |
724-02 - Hospital Regional Universitario Carlos Haya | Recruiting |
Málaga, Spain, 29010 | |
Contact: Manuel Benavides, MD | |
724-05 - Hospital Universitario Virgen del Rocío | Recruiting |
Sevilla, Spain, 41013 | |
Contact: Jerónimo Jímenez Castro, MD | |
Sweden | |
752-02 - Södersjukhuset | Recruiting |
Stockholm, Sweden, 118 83 | |
Contact: Pehr Lind, MD PhD | |
752-01 - Akademiska Sjukhuset | Recruiting |
Uppsala, Sweden, 751 85 | |
Contact: Peter Nygren, Prof. |
Principal Investigator: | Josep Tabernero, Prof. | Vall d'Hebron Institute of Oncology |
Responsible Party: | Isofol Medical AB |
ClinicalTrials.gov Identifier: | NCT03750786 |
Other Study ID Numbers: |
ISO-CC-007 |
First Posted: | November 23, 2018 Key Record Dates |
Last Update Posted: | January 15, 2021 |
Last Verified: | February 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases |
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