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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03750786
Recruitment Status : Active, not recruiting
First Posted : November 23, 2018
Last Update Posted : March 31, 2022
Sponsor:
Information provided by (Responsible Party):
Isofol Medical AB

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 490 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, 2022
Estimated Study Completion Date : January 31, 2023

Resource links provided by the National Library of Medicine


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




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.



Information from the National Library of Medicine

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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)

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


Locations
Hide Hide 94 study locations
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United States, Arizona
840-24 - Banner Gateway Medical Center
Gilbert, Arizona, United States, 85234
United States, California
840-01 - University of Southern California
Los Angeles, California, United States, 91001
840-15 - HOAG Memorial Hospital
Newport Beach, California, United States, 92663
United States, Colorado
840-13 - UCH-MHS d/b/a Memorial Health System
Colorado Springs, Colorado, United States, 80909
840-34 - Banner MD Anderson Cancer Center
Greeley, Colorado, United States, 80631
United States, Florida
840-32 - University of Miami
Miami, Florida, United States, 33136
840-08 - Pinellas Hematology Oncology
Saint Petersburg, Florida, United States, 33709
United States, Illinois
840-30 - Joliet Oncology-Hematology Associates
Joliet, Illinois, United States, 60435
United States, Kansas
840-06 - Cancer Center of Kansas
Wichita, Kansas, United States, 67214
United States, Kentucky
840-29 - Ashland-Bellefonte Cancer Center
Ashland, Kentucky, United States, 41101
840-19 - University of Louisville Research Foundation Inc. (ULRF)
Louisville, Kentucky, United States, 40202-1798
United States, Michigan
840-14 - University of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Montana
840-04 - St. Vincent Frontier Cancer Center
Billings, Montana, United States, 59102
United States, New Jersey
840-12 - Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, Oklahoma
840-22 - University of Oklahoma Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
840-10 - Oregon Health and Science University-Knight Cancer Institute
Portland, Oregon, United States, 97239
United States, South Carolina
840-27 - Charleston Hematology Oncology Associates
Charleston, South Carolina, United States, 29414
United States, Texas
840-02 - The University of Texas Health Science Center
San Antonio, Texas, United States, 78229
Australia, New South Wales
036-10 - Border Medical Oncology Research Unit
Albury, New South Wales, Australia, 2640
036-02 - Chris O'Brien Lifehouse
Sydney, New South Wales, Australia, 2050
036-03 - Westmead Hospital
Sydney, New South Wales, Australia, 2145
036-09 - Southern Medical Day Care Center
Wollongong, New South Wales, Australia, 2500
Australia, Victoria
036-04 - Peninsula Health - Frankston Hospital
Frankston, Victoria, Australia, 3199
036-01 - Western Health - Sunshine Hospital
Melbourne, Victoria, Australia, 3021
036-07 - Northern Health - Epping Hospital
Melbourne, Victoria, Australia, 3076
036-05 - Monash Health
Melbourne, Victoria, Australia, 3168
Austria
040-02 - Klinikum Klagenfurt am Wörthersee
Klagenfurt, Austria, 9020
040-06 - Ordensklinikum Linz GmbH - Barmherzige Schwestern
Linz, Austria, 4010
040-03 - Landeskrankenhaus
Salzburg, Austria, 5020
040-04 - Landesklinikum Wiener Neustadt
Wiener Neustadt, Austria, 2700
040-01 - Allgemeines Krankenhaus der Stadt Wien
Wien, Austria, 1090
040-05 - Wilhelminenspital
Wien, Austria, 1160
Canada, Ontario
124-03 - William Osler Health System - Brampton Civi Hospital
Brampton, Ontario, Canada, L6R 3J7
124-10 - Thunder Bay Regional Health Research Institute
Thunder Bay, Ontario, Canada, P7B 6V4
124-07 - Sunnybrook Research Institute
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
124-04 - CISSS de l'Outaouais - Hôpital de Gatineau
Gatineau, Quebec, Canada, J8V 2L4
124-11 - CISSS de Chaudière-Appalaches
Lévis, Quebec, Canada, G6V 3Z1
124-01 - Montreal University Health Center
Montreal, Quebec, Canada, H4A 3J1
Canada
124-02 - Hôpital de la Cité-de-la-Santé
Laval, Canada, H7M 3L9
124-08 - Hôpital Maisonneuve Rosemont
Montréal, Canada, H1T 2M4
124-06 - Jewish General Hospital
Montréal, Canada, H3T 1E2
124-05 - Ottawa Hospital Research Institute
Ottawa, Canada, KIH8L6
France
250-07 - Hôpital Henri Mondor
Créteil, France, 94010
250-06 - Centre Georges Francois Leclerc
Dijon, France, 21000
250-01 - Institute Hospitalier Franco-Britannique
Levallois-Perret, France, 92300
250-09 - Hopital Privé Jean Mermoz
Lyon, France, 69373
250-08 - Hôpital Européen
Marseille, France, 13003
250-03 - Hôpital Paris Saint Joseph
Paris, France, 75014
250-02 - Hôpital Saint-Antoine
Paris, France, 75571
250-04 - Polyclinique Francheville
Périgueux, France, 24000
250-05 - Clinique Sainte Anne
Strasbourg, France, 67000
Germany
276-12 - Charité - Universitätsmedizin Berlin
Berlin, Germany, 10117
276-02 - Universitätsklinikum Carl Gustav Carus
Dresden, Germany, 01307
276-03 - Krankenhaus Nordwest GmbH
Frankfurt am Main, Germany, 60488
276-10 - Universitärers Cancer Center Hamburg (UCCH)
Hamburg, Germany, 20246
276-11 - Klinikum Kassel GmbH
Kassel, Germany, 34125
276-04 - MVZ Mitte - Onkologische Schwerpunktpraxis
Leipzig, Germany, 04103
276-13 - Universitäres Krebszentrum Leipzig (UCCL)
Leipzig, Germany, 04103
276-07 - Philipps-Universität Marburg
Marburg, Germany, 35032
276-08 - Carl von Basedow Klinikum Saalekrei GmbH
Merseburg, Germany, 06217
276-01 - Klinikum der Universität München - Campus Grosshadern
München, Germany, 81377
276-09 - Klinikum Nürnberg Nord
Nürnberg, Germany, 90419
276-05 - Kliniken Nordoberpfalz AG
Weiden, Germany, 92637
Greece
300-04 - 251 Airforce Hospital
Athens, Greece, 11525
300-01 - Aretaieo Hospital
Athens, Greece, 11528
300-02 - University General Hospital Attikon
Athens, Greece, 15562
300-03 - Metropolitan General Hospital
Athens, Greece, 15562
300-05 - Metropolitan General SA
Athen, Greece, 15562
300-06 - University General Hospital of Larissa
Larissa, Greece, 41110
Japan
392-10 - Aichi Cancer Center
Aichi, Japan, 464-8681
392-01 - National Cancer Center Hospital East
Chiba, Japan, 277-8577
392-09 - National Hospital Organization Shikoku Cancer Center
Ehime, Japan, 791-0280
392-07 - Gifu University Hospital
Gifu City, Japan, 501-1194
392-12 - Saitama Medical University International Medical Center
Hidaka City, Japan, 350-1298
392-05 - University of Tsukuba Hospital
Ibaraki, Japan, 305-8576
392-15 - Kagawa University Hospital
Kagawa, Japan, 761-0793
392-08 - St.Marianna University School of Medicine Hospital
Kanagawa, Japan, 216-8511
392-11 - National Hospital Organization Osaka National Hospital
Osaka, Japan, 540-0006
392-13 - Osaka General Medical Center
Osaka, Japan, 558-8558
392-14 - Kansai Medical University Hospital
Osaka, Japan, 573-1191
392-04 - Saitama Cancer Center
Saitama, Japan, 362-0806
392-03 - Hokkaido University Hospital
Sapporo Hokkaido, Japan, 060-8648
392-02 - Shizuoka Cancer Center
Shizuoka, Japan, 411-8777
392-06 - National Cancer Center Hospital
Tokyo, Japan, 104-0045
Spain
724-03 - Instituto Oncologico Baselga - Hospital Quiron
Barcelona, Spain, 08023
724-07 - Hospital del la Santa Creu i Sant Pau
Barcelona, Spain, 08026
724-01 - Vall d'Hebron Institute of Oncology
Barcelona, Spain, 08035
724-06 - Hospital Universitario Reina Sofia
Córdoba, Spain, 14004
724-04 - Hospital Unviersitario 12 de Octubre
Madrid, Spain, 28041
724-09 - Hospital Universitario HM Sanchinarro
Madrid, Spain, 28050
724-02 - Hospital Regional Universitario Carlos Haya
Málaga, Spain, 29010
724-05 - Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
Sweden
752-02 - Södersjukhuset
Stockholm, Sweden, 118 83
752-01 - Akademiska Sjukhuset
Uppsala, Sweden, 751 85
Sponsors and Collaborators
Isofol Medical AB
Investigators
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Principal Investigator: Josep Tabernero, Prof. Vall d'Hebron Institute of Oncology
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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: March 31, 2022
Last Verified: September 2021

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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
Leucovorin
Antidotes
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients