A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer
- Registration Number
- NCT03750786
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 490
- 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performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A Arfolitixorin ARFOX (Arfolitixorin and 5-FU and Oxaliplatin) and Bevacizumab Group B Leucovorin mFOLFOX-6 (Leucovorin and 5-FU and Oxaliplatin) and Bevacizumab
- Primary Outcome Measures
Name Time Method Overall Response Rate 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
Name Time Method Progression Free Survival 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 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.
Trial Locations
- Locations (94)
840-01 - HOAG Memorial Hospital
🇺🇸Newport Beach, California, United States
124-11 - CISSS de Chaudière-Appalaches
🇨🇦Lévis, Quebec, Canada
250-05 - Clinique Sainte Anne
🇫🇷Strasbourg, France
300-01 - Aretaieo Hospital
🇬🇷Athens, Greece
300-03 - Metropolitan General Hospital
🇬🇷Athens, Greece
392-01 - National Cancer Center Hospital East
🇯🇵Chiba, Japan
392-05 - University of Tsukuba Hospital
🇯🇵Ibaraki, Japan
392-08 - St.Marianna University School of Medicine Hospital
🇯🇵Kanagawa, Japan
300-05 - Metropolitan General SA
🇬🇷Athen, Greece
300-06 - University General Hospital of Larissa
🇬🇷Larissa, Greece
392-10 - Aichi Cancer Center
🇯🇵Aichi, Japan
840-32 - University of Miami
🇺🇸Miami, Florida, United States
840-02 - The University of Texas Health Science Center
🇺🇸San Antonio, Texas, United States
840-13 - UCH-MHS d/b/a Memorial Health System
🇺🇸Colorado Springs, Colorado, United States
840-22 - University of Oklahoma Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
840-34 - Banner MD Anderson Cancer Center
🇺🇸Greeley, Colorado, United States
840-04 - St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
036-03 - Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
036-09 - Southern Medical Day Care Center
🇦🇺Wollongong, New South Wales, Australia
124-03 - William Osler Health System - Brampton Civi Hospital
🇨🇦Brampton, Ontario, Canada
040-05 - Wilhelminenspital
🇦🇹Wien, Austria
124-07 - Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
276-01 - Klinikum der Universität München - Campus Grosshadern
🇩🇪München, Germany
392-07 - Gifu University Hospital
🇯🇵Gifu City, Japan
276-04 - MVZ Mitte - Onkologische Schwerpunktpraxis
🇩🇪Leipzig, Germany
276-09 - Klinikum Nürnberg Nord
🇩🇪Nürnberg, Germany
276-05 - Kliniken Nordoberpfalz AG
🇩🇪Weiden, Germany
300-04 - 251 Airforce Hospital
🇬🇷Athens, Greece
392-09 - National Hospital Organization Shikoku Cancer Center
🇯🇵Ehime, Japan
392-12 - Saitama Medical University International Medical Center
🇯🇵Hidaka City, Japan
300-02 - University General Hospital Attikon
🇬🇷Athens, Greece
392-14 - Kansai Medical University Hospital
🇯🇵Osaka, Japan
392-15 - Kagawa University Hospital
🇯🇵Kagawa, Japan
392-04 - Saitama Cancer Center
🇯🇵Saitama, Japan
392-02 - Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
392-06 - National Cancer Center Hospital
🇯🇵Tokyo, Japan
724-03 - Instituto Oncologico Baselga - Hospital Quiron
🇪🇸Barcelona, Spain
752-01 - Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
724-07 - Hospital del la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
724-01 - Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
724-04 - Hospital Unviersitario 12 de Octubre
🇪🇸Madrid, Spain
724-09 - Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
724-02 - Hospital Regional Universitario Carlos Haya
🇪🇸Málaga, Spain
752-02 - Södersjukhuset
🇸🇪Stockholm, Sweden
724-05 - Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
724-06 - Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
840-29 - Ashland-Bellefonte Cancer Center
🇺🇸Ashland, Kentucky, United States
840-15 - University of Southern California
🇺🇸Los Angeles, California, United States
840-06 - Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
840-30 - Joliet Oncology-Hematology Associates
🇺🇸Joliet, Illinois, United States
840-19 - University of Louisville Research Foundation Inc. (ULRF)
🇺🇸Louisville, Kentucky, United States
840-12 - Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
840-10 - Oregon Health and Science University-Knight Cancer Institute
🇺🇸Portland, Oregon, United States
840-27 - Charleston Hematology Oncology Associates
🇺🇸Charleston, South Carolina, United States
036-10 - Border Medical Oncology Research Unit
🇦🇺Albury, New South Wales, Australia
036-02 - Chris O'Brien Lifehouse
🇦🇺Sydney, New South Wales, Australia
036-01 - Western Health - Sunshine Hospital
🇦🇺Melbourne, Victoria, Australia
036-07 - Northern Health - Epping Hospital
🇦🇺Melbourne, Victoria, Australia
040-06 - Ordensklinikum Linz GmbH - Barmherzige Schwestern
🇦🇹Linz, Austria
036-05 - Monash Health
🇦🇺Melbourne, Victoria, Australia
040-02 - Klinikum Klagenfurt am Wörthersee
🇦🇹Klagenfurt, Austria
040-03 - Uniklinikum Salzburg
🇦🇹Salzburg, Austria
040-04 - Landesklinikum Wiener Neustadt
🇦🇹Wiener Neustadt, Austria
040-01 - Allgemeines Krankenhaus der Stadt Wien
🇦🇹Wien, Austria
124-10 - Thunder Bay Regional Health Research Institute
🇨🇦Thunder Bay, Ontario, Canada
124-06 - Jewish General Hospital
🇨🇦Montréal, Canada
124-05 - Ottawa Hospital Research Institute
🇨🇦Ottawa, Canada
250-04 - Polyclinique Francheville
🇫🇷Périgueux, France
250-07 - Hôpital Henri Mondor
🇫🇷Créteil, France
250-06 - Centre Georges Francois Leclerc
🇫🇷Dijon, France
250-09 - Hopital Privé Jean Mermoz
🇫🇷Lyon, France
250-02 - Hôpital Saint-Antoine
🇫🇷Paris, France
250-08 - Hôpital Européen
🇫🇷Marseille, France
250-01 - Institute Hospitalier Franco-Britannique
🇫🇷Levallois-Perret, France
250-03 - Hôpital Paris Saint Joseph
🇫🇷Paris, France
276-03 - Krankenhaus Nordwest GmbH
🇩🇪Frankfurt am Main, Germany
276-12 - Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
276-02 - Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
276-11 - Klinikum Kassel GmbH
🇩🇪Kassel, Germany
276-08 - Carl von Basedow Klinikum Saalekrei GmbH
🇩🇪Merseburg, Germany
276-13 - Universitäres Krebszentrum Leipzig (UCCL)
🇩🇪Leipzig, Germany
276-07 - Philipps-Universität Marburg
🇩🇪Marburg, Germany
840-24 - Banner Gateway Medical Center
🇺🇸Gilbert, Arizona, United States
840-08 - Pinellas Hematology Oncology
🇺🇸Saint Petersburg, Florida, United States
124-01 - Montreal University Health Center
🇨🇦Montreal, Quebec, Canada
124-02 - Hôpital de la Cité-de-la-Santé
🇨🇦Laval, Canada
124-08 - Hôpital Maisonneuve Rosemont
🇨🇦Montréal, Canada
840-14 - University of Michigan Cancer Center
🇺🇸Ann Arbor, Michigan, United States
036-04 - Peninsula Health - Frankston Hospital
🇦🇺Frankston, Victoria, Australia
124-04 - CISSS de l'Outaouais - Hôpital de Gatineau
🇨🇦Gatineau, Quebec, Canada
276-10 - Universitärers Cancer Center Hamburg (UCCH)
🇩🇪Hamburg, Germany
392-11 - National Hospital Organization Osaka National Hospital
🇯🇵Osaka, Japan
392-13 - Osaka General Medical Center
🇯🇵Osaka, Japan
392-03 - Hokkaido University Hospital
🇯🇵Sapporo Hokkaido, Japan