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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)

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 27, 2020
Sponsor:
Information provided by (Responsible Party):
Isofol Medical AB

Study Description
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Brief 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 RECIST 1.1 criteria.

Condition or disease Intervention/treatment Phase
Colo-rectal Cancer Drug: Arfolitixorin Drug: Leucovorin Phase 3

Study Design
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


Eligibility Criteria
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Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Colorectal adenocarcinoma verified by biopsy.
  2. Availability of biopsy material, from the primary tumor or metastasis, allowing for analysis of tumor gene expression.
  3. Non-resectable metastatic CRC planned for first line therapy with 5-FU, oxaliplatin, and bevacizumab.
  4. 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.
  5. Life expectancy of more than 4 months.
  6. ECOG performance status 0 or 1.
  7. Hemoglobin (Hb) > 100 g/L, Absolute neutrophil count (ANC) > 1.5x109/L. Thrombocytes > 100x109/L.
  8. 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).
  9. Male or female ≥18 years of age.
  10. Female patients of childbearing potential must have a negative urine pregnancy test and use adequate contraceptive measures . Male patients must use adequate contraceptive measures .
  11. 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:

  1. 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.
  2. 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.)
  3. Confirmation of progressive disease within 6 months after completion of prior anti-cancer treatment.
  4. Indication for any metastatic Colo-rectal Cancer (mCRC) surgery or anti-cancer treatment other than study treatment.
  5. Prior treatment with arfolitixorin.
  6. Indication for treatment with a 5-FU analogue, or 5-FU for a condition other than mCRC.
  7. Known Dihydropyrimidine Dehydrogenase Deficiency (DPD) deficiency.
  8. Known or suspected central nervous system (CNS) metastases.
  9. Unresolved bowel obstruction, uncontrolled Crohn's disease, or ulcerative colitis.
  10. 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.
  11. Current CTCAE ≥ grade 3 diarrhea.
  12. Current chronic infection or uncontrolled serious illness causing immunodeficiency.
  13. Known or suspected hypersensitivity or intolerance to arfolitixorin, LV, 5-FU, oxaliplatin, or bevacizumab.
  14. Breastfeeding patients.
  15. Patient who received investigational drugs in other clinical trials within 28 days, or 5 half-lives of the investigational drug, prior to randomization.
  16. Patient with serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  17. Ongoing drug or alcohol abuse, as deemed by the Investigator.
  18. Any condition that, in the opinion of the Investigator, could compromise the patient's safety or adherence to the study protocol.
  19. 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)
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Roger Tell, MD, PhD +46 (0) 760 293 911 roger.tell@isofolmedical.com

Locations
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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 Recruiting
Washington, District of Columbia, United States, 20057
Contact: Benjamin Weinberg, MD         
United States, Florida
840-32 - University of Miami Not yet 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 Recruiting
Evanston, Illinois, United States, 60201
Contact: Marisa Hill, MD         
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 Recruiting
Detroit, Michigan, United States, 48201
Contact: Philip Philip, MD         
840-36 - Clinical Oncology Associates Recruiting
Farmington Hills, Michigan, United States, 48334
Contact: Craig Gordon, MD         
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 Recruiting
Buffalo, New York, United States, 14263
Contact: Sarbajit Mukherjee, MD         
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 Recruiting
Abington, Pennsylvania, United States, 19001
Contact: Steve Cohen, MD         
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
840-37 - Oncology & Hematology of South Texas Not yet recruiting
Laredo, Texas, United States, 78041
Contact: Eduardo Miranda, MD         
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 Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Stacey Cohen, MD         
Australia, New South Wales
036-10 - Border Medical Oncology Research Unit Not yet recruiting
Albury, New South Wales, Australia, 2640
Contact: Craig Underhill, MD         
036-02 - Chris O'Brien Lifehouse Not yet 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 Not yet 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 Not yet recruiting
Adelaide, South Australia, Australia, 5037
Contact: Francis Parnis, MD         
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 Not yet 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 Not yet 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: Yoo-Joung Ko, 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 Not yet 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
276-02 - 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 - Metropolitan General Hospital 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         
392-02 - 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 Recruiting
Madrid, Spain, 28034
Contact: Mercedes Rodríguez Garrote, MD         
724-04 - Hospital Unviersitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Cristina Gravalos, 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.         
Sponsors and Collaborators
Isofol Medical AB
Investigators
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Principal Investigator: Josep Tabernero, Prof. Vall d'Hebron Institute of Oncology
More Information
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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 27, 2020
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Oxaliplatin
 Fluorouracil
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors