We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
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


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Show Show 94 study locations
Sponsors and Collaborators
Isofol Medical AB
Investigators
Layout table for investigator information
Principal Investigator: Josep Tabernero, Prof. Vall d'Hebron Institute of Oncology
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
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