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

NCT03750786 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ISO-CC-007
• Study Type: interventional
• Target: 490
• Locations: 9 countries
• Sites: 86

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.

Conditions

Colo-rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

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

  Until disease progression, an average of ten months

Secondary Outcomes (2)

• Progression Free Survival

  Until disease progression, an average of ten months

• Duration of Response

  Until disease progression, an average of ten months

Study Arms (2)

Group A

EXPERIMENTAL

ARFOX (Arfolitixorin and 5-FU and Oxaliplatin) and Bevacizumab

Drug: Arfolitixorin

Group B

ACTIVE COMPARATOR

mFOLFOX-6 (Leucovorin and 5-FU and Oxaliplatin) and Bevacizumab

Drug: Leucovorin

Interventions

Arfolitixorin DRUG

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

Group A

Leucovorin DRUG

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

Group B

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Isofol Medical AB: lead

Study Sites (94)

840-24 - Banner Gateway Medical Center

Gilbert, Arizona, 85234, United States

Location

840-15 - University of Southern California

Los Angeles, California, 91001, United States

Location

840-01 - HOAG Memorial Hospital

Newport Beach, California, 92663, United States

Location

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

Colorado Springs, Colorado, 80909, United States

Location

840-34 - Banner MD Anderson Cancer Center

Greeley, Colorado, 80631, United States

Location

840-32 - University of Miami

Miami, Florida, 33136, United States

Location

840-08 - Pinellas Hematology Oncology

St. Petersburg, Florida, 33709, United States

Location

840-30 - Joliet Oncology-Hematology Associates

Joliet, Illinois, 60435, United States

Location

840-06 - Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

840-29 - Ashland-Bellefonte Cancer Center

Ashland, Kentucky, 41101, United States

Location

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

Louisville, Kentucky, 40202-1798, United States

Location

840-14 - University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

840-04 - St. Vincent Frontier Cancer Center

Billings, Montana, 59102, United States

Location

840-12 - Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

840-22 - University of Oklahoma Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

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

Portland, Oregon, 97239, United States

Location

840-27 - Charleston Hematology Oncology Associates

Charleston, South Carolina, 29414, United States

Location

840-02 - The University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

036-10 - Border Medical Oncology Research Unit

Albury, New South Wales, 2640, Australia

Location

036-02 - Chris O'Brien Lifehouse

Sydney, New South Wales, 2050, Australia

Location

036-03 - Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

036-09 - Southern Medical Day Care Center

Wollongong, New South Wales, 2500, Australia

Location

036-04 - Peninsula Health - Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

036-01 - Western Health - Sunshine Hospital

Melbourne, Victoria, 3021, Australia

Location

036-07 - Northern Health - Epping Hospital

Melbourne, Victoria, 3076, Australia

Location

036-05 - Monash Health

Melbourne, Victoria, 3168, Australia

Location

040-02 - Klinikum Klagenfurt am Wörthersee

Klagenfurt, 9020, Austria

Location

040-06 - Ordensklinikum Linz GmbH - Barmherzige Schwestern

Linz, 4010, Austria

Location

040-03 - Uniklinikum Salzburg

Salzburg, 5020, Austria

Location

040-01 - Allgemeines Krankenhaus der Stadt Wien

Vienna, 1090, Austria

Location

040-05 - Wilhelminenspital

Vienna, 1160, Austria

Location

040-04 - Landesklinikum Wiener Neustadt

Wiener Neustadt, 2700, Austria

Location

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

Brampton, Ontario, L6R 3J7, Canada

Location

124-10 - Thunder Bay Regional Health Research Institute

Thunder Bay, Ontario, P7B 6V4, Canada

Location

124-07 - Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

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

Gatineau, Quebec, J8V 2L4, Canada

Location

124-11 - CISSS de Chaudière-Appalaches

Lévis, Quebec, G6V 3Z1, Canada

Location

124-01 - Montreal University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

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

Laval, H7M 3L9, Canada

Location

124-08 - Hôpital Maisonneuve Rosemont

Montreal, H1T 2M4, Canada

Location

124-06 - Jewish General Hospital

Montreal, H3T 1E2, Canada

Location

124-05 - Ottawa Hospital Research Institute

Ottawa, KIH8L6, Canada

Location

250-07 - Hôpital Henri Mondor

Créteil, 94010, France

Location

250-06 - Centre Georges Francois Leclerc

Dijon, 21000, France

Location

250-01 - Institute Hospitalier Franco-Britannique

Levallois-Perret, 92300, France

Location

250-09 - Hopital Privé Jean Mermoz

Lyon, 69373, France

Location

250-08 - Hôpital Européen

Marseille, 13003, France

Location

250-03 - Hôpital Paris Saint Joseph

Paris, 75014, France

Location

250-02 - Hôpital Saint-Antoine

Paris, 75571, France

Location

250-04 - Polyclinique Francheville

Périgueux, 24000, France

Location

250-05 - Clinique Sainte Anne

Strasbourg, 67000, France

Location

276-12 - Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

276-02 - Universitätsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

276-03 - Krankenhaus Nordwest GmbH

Frankfurt am Main, 60488, Germany

Location

276-10 - Universitärers Cancer Center Hamburg (UCCH)

Hamburg, 20246, Germany

Location

276-11 - Klinikum Kassel GmbH

Kassel, 34125, Germany

Location

276-04 - MVZ Mitte - Onkologische Schwerpunktpraxis

Leipzig, 04103, Germany

Location

276-13 - Universitäres Krebszentrum Leipzig (UCCL)

Leipzig, 04103, Germany

Location

276-07 - Philipps-Universität Marburg

Marburg, 35032, Germany

Location

276-08 - Carl von Basedow Klinikum Saalekrei GmbH

Merseburg, 06217, Germany

Location

276-01 - Klinikum der Universität München - Campus Grosshadern

München, 81377, Germany

Location

276-09 - Klinikum Nürnberg Nord

Nuremberg, 90419, Germany

Location

276-05 - Kliniken Nordoberpfalz AG

Weiden, 92637, Germany

Location

300-04 - 251 Airforce Hospital

Athens, 11525, Greece

Location

300-01 - Aretaieo Hospital

Athens, 11528, Greece

Location

300-02 - University General Hospital Attikon

Athens, 15562, Greece

Location

300-03 - Metropolitan General Hospital

Athens, 15562, Greece

Location

300-05 - Metropolitan General SA

Athens, 15562, Greece

Location

300-06 - University General Hospital of Larissa

Larissa, 41110, Greece

Location

392-10 - Aichi Cancer Center

Aichi, 464-8681, Japan

Location

392-01 - National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

392-09 - National Hospital Organization Shikoku Cancer Center

Ehime, 791-0280, Japan

Location

392-07 - Gifu University Hospital

Gifu, 501-1194, Japan

Location

392-12 - Saitama Medical University International Medical Center

Hidaka, 350-1298, Japan

Location

392-05 - University of Tsukuba Hospital

Ibaraki, 305-8576, Japan

Location

392-15 - Kagawa University Hospital

Kagawa, 761-0793, Japan

Location

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

Kanagawa, 216-8511, Japan

Location

392-11 - National Hospital Organization Osaka National Hospital

Osaka, 540-0006, Japan

Location

392-13 - Osaka General Medical Center

Osaka, 558-8558, Japan

Location

392-14 - Kansai Medical University Hospital

Osaka, 573-1191, Japan

Location

392-04 - Saitama Cancer Center

Saitama, 362-0806, Japan

Location

392-03 - Hokkaido University Hospital

Sapporo Hokkaido, 060-8648, Japan

Location

392-02 - Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

392-06 - National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

724-03 - Instituto Oncologico Baselga - Hospital Quiron

Barcelona, 08023, Spain

Location

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

Barcelona, 08026, Spain

Location

724-01 - Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

724-06 - Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

724-04 - Hospital Unviersitario 12 de Octubre

Madrid, 28041, Spain

Location

724-09 - Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

724-02 - Hospital Regional Universitario Carlos Haya

Málaga, 29010, Spain

Location

724-05 - Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

752-02 - Södersjukhuset

Stockholm, 118 83, Sweden

Location

752-01 - Akademiska Sjukhuset

Uppsala, 751 85, Sweden

Location

Related Publications (1)

• 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.

  PMID: 38059497 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Leucovorin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Karin Gedda
• Organization: Isofol

karin.gedda@isofolmedical.com

+46 (0) 729 9453 37

Study Officials

• Josep Tabernero, Prof.

  Vall d'Hebron Institute of Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 23, 2018
• Study Start: December 18, 2018
• Primary Completion: November 18, 2022
• Study Completion: November 18, 2022
• Last Updated: October 26, 2023
• Results First Posted: October 26, 2023

Record last verified: 2023-10

Locations

SE (2); JP (15); GR (6); CA (10); US (18); AU (6); FR (9); DE (12); ES (8)