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)
- Conditions
- Colo-rectal Cancer
- Registration Number
- JPRN-jRCT2080224951
- Lead Sponsor
- Isofol Medical AB / CMIC Shiftzero K.K
- Brief Summary
The study failed to demonstrate clinical benefit of arfolitixorin (120 mg/m2) over leucovorin. However, it provides some useful insights from the first-line treatment setting, including the effect of gene expression on outcomes.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 490
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 or more in longest diameter on axial image on CT-scan or alternatively MRI with less than 5 mm reconstruction interval) or lymph node (15 mm or more 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) more than 80 g/L, Absolute neutrophil count (ANC) more than 1.5 times 10E9/L. Thrombocytes more than 100 times 10E9/L.
8.Creatinine clearance more than 50 mL/min, Total bilirubin less than 1.5 times ULN, AST and ALT less than 3 times ULN (and less than 5 times ULN in case of liver metastases).
9.Male or female 18 years of age or older.
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performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
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 Crohns 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 or higher.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall response rate [ Time Frame: Until disease progression, an average of ten months ]<br>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 [ Time Frame: Until disease progression, an average of ten months ]<br>PFS, defined as the time from randomization to first occurrence of tumor progression based on CT-scans/MRIs.<br>Duration of response [ Time Frame: Until disease progression, an average of ten months ]<br>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.