Clinical trial NCT03750786: A Study to Compare the Efficacy of Arfolitixorin Versus Leucovorin in Combination With 5 Fluorouracil, Oxaliplatin, and Bevacizumab in Patients With Advanced Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colo-rectal Cancer
Lead sponsor: Isofol Medical AB
Sponsor class: INDUSTRY
First posted: 2018-11-23
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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, Leucovorin, 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) or lymph node (≥ 15 mm in shortest axis when assessed by CT) obtained within 28 days of randomization.
5. Life expectancy of more than 4 months.
6. ECOG performance status 0 or 1.
7. Hemoglobin (Hb) \> 80 g/L, Absolute neutrophil count (ANC) \> 1.5x10E9/L. Thrombocytes \> 100x10E9/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, 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 adjuvant 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)
20. Surgery (excluding previous diagnostic biopsy) in the 28-day period before randomization

Primary outcomes:
measure: Overall Response Rate
timeFrame: Until disease progression, an average of ten months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Until disease progression, an average of ten months
measure: Duration of Response
timeFrame: Until disease progression, an average of ten months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: 840-24 - Banner Gateway Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: 840-15 - University of Southern California
state: California
city: Newport Beach
country: United States
facility: 840-01 - HOAG Memorial Hospital
state: California
city: Colorado Springs
country: United States
facility: 840-13 - UCH-MHS d/b/a Memorial Health System
state: Colorado
city: Greeley
country: United States
facility: 840-34 - Banner MD Anderson Cancer Center
state: Colorado
city: Miami
country: United States
facility: 840-32 - University of Miami
state: Florida
city: Saint Petersburg
country: United States
facility: 840-08 - Pinellas Hematology Oncology
state: Florida
city: Joliet
country: United States
facility: 840-30 - Joliet Oncology-Hematology Associates
state: Illinois
city: Wichita
country: United States
facility: 840-06 - Cancer Center of Kansas
state: Kansas
city: Ashland
country: United States
facility: 840-29 - Ashland-Bellefonte Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: 840-19 - University of Louisville Research Foundation Inc. (ULRF)
state: Kentucky
city: Ann Arbor
country: United States
facility: 840-14 - University of Michigan Cancer Center
state: Michigan
city: Billings
country: United States
facility: 840-04 - St. Vincent Frontier Cancer Center
state: Montana
city: New Brunswick
country: United States
facility: 840-12 - Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Oklahoma City
country: United States
facility: 840-22 - University of Oklahoma Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: 840-10 - Oregon Health and Science University-Knight Cancer Institute
state: Oregon
city: Charleston
country: United States
facility: 840-27 - Charleston Hematology Oncology Associates
state: South Carolina
city: San Antonio
country: United States
facility: 840-02 - The University of Texas Health Science Center
state: Texas
city: Albury
country: Australia
facility: 036-10 - Border Medical Oncology Research Unit
state: New South Wales
city: Sydney
country: Australia
facility: 036-02 - Chris O'Brien Lifehouse
state: New South Wales
city: Sydney
country: Australia
facility: 036-03 - Westmead Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: 036-09 - Southern Medical Day Care Center
state: New South Wales
city: Frankston
country: Australia
facility: 036-04 - Peninsula Health - Frankston Hospital
state: Victoria
city: Melbourne
country: Australia
facility: 036-01 - Western Health - Sunshine Hospital
state: Victoria
city: Melbourne
country: Australia
facility: 036-07 - Northern Health - Epping Hospital
state: Victoria
city: Melbourne
country: Australia
facility: 036-05 - Monash Health
state: Victoria
city: Klagenfurt
country: Austria
facility: 040-02 - Klinikum Klagenfurt am Wörthersee
city: Linz
country: Austria
facility: 040-06 - Ordensklinikum Linz GmbH - Barmherzige Schwestern
city: Salzburg
country: Austria
facility: 040-03 - Uniklinikum Salzburg
city: Wiener Neustadt
country: Austria
facility: 040-04 - Landesklinikum Wiener Neustadt
city: Wien
country: Austria
facility: 040-01 - Allgemeines Krankenhaus der Stadt Wien
city: Wien
country: Austria
facility: 040-05 - Wilhelminenspital
city: Brampton
country: Canada
facility: 124-03 - William Osler Health System - Brampton Civi Hospital
state: Ontario
city: Thunder Bay
country: Canada
facility: 124-10 - Thunder Bay Regional Health Research Institute
state: Ontario
city: Toronto
country: Canada
facility: 124-07 - Sunnybrook Research Institute
state: Ontario
city: Gatineau
country: Canada
facility: 124-04 - CISSS de l'Outaouais - Hôpital de Gatineau
state: Quebec
city: Lévis
country: Canada
facility: 124-11 - CISSS de Chaudière-Appalaches
state: Quebec
city: Montreal
country: Canada
facility: 124-01 - Montreal University Health Center
state: Quebec
city: Laval
country: Canada
facility: 124-02 - Hôpital de la Cité-de-la-Santé
city: Montréal
country: Canada
facility: 124-08 - Hôpital Maisonneuve Rosemont
city: Montréal
country: Canada
facility: 124-06 - Jewish General Hospital
city: Ottawa
country: Canada
facility: 124-05 - Ottawa Hospital Research Institute
city: Créteil
country: France
facility: 250-07 - Hôpital Henri Mondor
city: Dijon
country: France
facility: 250-06 - Centre Georges Francois Leclerc
city: Levallois-Perret
country: France
facility: 250-01 - Institute Hospitalier Franco-Britannique
city: Lyon
country: France
facility: 250-09 - Hopital Privé Jean Mermoz
city: Marseille
country: France
facility: 250-08 - Hôpital Européen
city: Paris
country: France
facility: 250-03 - Hôpital Paris Saint Joseph
city: Paris
country: France
facility: 250-02 - Hôpital Saint-Antoine
city: Périgueux
country: France
facility: 250-04 - Polyclinique Francheville
city: Strasbourg
country: France
facility: 250-05 - Clinique Sainte Anne
city: Berlin
country: Germany
facility: 276-12 - Charité - Universitätsmedizin Berlin
city: Dresden
country: Germany
facility: 276-02 - Universitätsklinikum Carl Gustav Carus
city: Frankfurt am Main
country: Germany
facility: 276-03 - Krankenhaus Nordwest GmbH
city: Hamburg
country: Germany
facility: 276-10 - Universitärers Cancer Center Hamburg (UCCH)
city: Kassel
country: Germany
facility: 276-11 - Klinikum Kassel GmbH
city: Leipzig
country: Germany
facility: 276-04 - MVZ Mitte - Onkologische Schwerpunktpraxis
city: Leipzig
country: Germany
facility: 276-13 - Universitäres Krebszentrum Leipzig (UCCL)
city: Marburg
country: Germany
facility: 276-07 - Philipps-Universität Marburg
city: Merseburg
country: Germany
facility: 276-08 - Carl von Basedow Klinikum Saalekrei GmbH
city: München
country: Germany
facility: 276-01 - Klinikum der Universität München - Campus Grosshadern
city: Nürnberg
country: Germany
facility: 276-09 - Klinikum Nürnberg Nord
city: Weiden
country: Germany
facility: 276-05 - Kliniken Nordoberpfalz AG
city: Athens
country: Greece
facility: 300-04 - 251 Airforce Hospital
city: Athens
country: Greece
facility: 300-01 - Aretaieo Hospital
city: Athens
country: Greece
facility: 300-02 - University General Hospital Attikon
city: Athens
country: Greece
facility: 300-03 - Metropolitan General Hospital
city: Athen
country: Greece
facility: 300-05 - Metropolitan General SA
city: Larissa
country: Greece
facility: 300-06 - University General Hospital of Larissa
city: Aichi
country: Japan
facility: 392-10 - Aichi Cancer Center
city: Chiba
country: Japan
facility: 392-01 - National Cancer Center Hospital East
city: Ehime
country: Japan
facility: 392-09 - National Hospital Organization Shikoku Cancer Center
city: Gifu City
country: Japan
facility: 392-07 - Gifu University Hospital
city: Hidaka City
country: Japan
facility: 392-12 - Saitama Medical University International Medical Center
city: Ibaraki
country: Japan
facility: 392-05 - University of Tsukuba Hospital
city: Kagawa
country: Japan
facility: 392-15 - Kagawa University Hospital
city: Kanagawa
country: Japan
facility: 392-08 - St.Marianna University School of Medicine Hospital
city: Osaka
country: Japan
facility: 392-11 - National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: 392-13 - Osaka General Medical Center
city: Osaka
country: Japan
facility: 392-14 - Kansai Medical University Hospital
city: Saitama
country: Japan
facility: 392-04 - Saitama Cancer Center
city: Sapporo Hokkaido
country: Japan
facility: 392-03 - Hokkaido University Hospital
city: Shizuoka
country: Japan
facility: 392-02 - Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: 392-06 - National Cancer Center Hospital
city: Barcelona
country: Spain
facility: 724-03 - Instituto Oncologico Baselga - Hospital Quiron
city: Barcelona
country: Spain
facility: 724-07 - Hospital del la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: 724-01 - Vall d'Hebron Institute of Oncology
city: Córdoba
country: Spain
facility: 724-06 - Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: 724-04 - Hospital Unviersitario 12 de Octubre
city: Madrid
country: Spain
facility: 724-09 - Hospital Universitario HM Sanchinarro
city: Málaga
country: Spain
facility: 724-02 - Hospital Regional Universitario Carlos Haya
city: Sevilla
country: Spain
facility: 724-05 - Hospital Universitario Virgen del Rocío
city: Stockholm
country: Sweden
facility: 752-02 - Södersjukhuset
city: Uppsala
country: Sweden
facility: 752-01 - Akademiska Sjukhuset
Study officials:
affiliation: Vall d'Hebron Institute of Oncology
name: Josep Tabernero, Prof.
role: PRINCIPAL_INVESTIGATOR
References: