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

Colo-rectal Cancer Clinical Trial

— AGENT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03750786
• Other study ID #: ISO-CC-007
• Status: Completed
• Phase: Phase 3
• Start date: December 18, 2018
• Est. completion date: November 18, 2022

Study information

• Verified date: October 2023
• Source: Isofol Medical AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 490
• Est. completion date: November 18, 2022
• Est. primary completion date: November 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colo-rectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Arfolitixorin
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
• Leucovorin
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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Isofol Medical AB

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  France,  Germany,  Greece,  Japan,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression Free Survival	PFS, defined as the time from randomization to first occurrence of tumor progression based on CT-scans/MRIs.	Until disease progression, an average of ten months
Secondary	Duration of Response	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.	Until disease progression, an average of ten months