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)

• ClinicalTrials.gov Identifier: NCT03750786
• Recruitment Status: Recruiting
• First Posted: November 23, 2018
• Last Update Posted: January 15, 2021
• Sponsor: Isofol Medical AB
• Information provided by (Responsible Party): Isofol Medical AB

Tracking Information

• First Submitted Date: November 19, 2018
• First Posted Date: November 23, 2018
• Last Update Posted Date: January 15, 2021
• Actual Study Start Date: December 18, 2018
• Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2018)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2018)

• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Colo-rectal Cancer

Intervention

• Drug: Arfolitixorin
  Arfolitixorin and 5-FU and Oxaliplatin and Bevacizumab
• Drug: Leucovorin
  Leucovorin and 5-FU and Oxaliplatin and Bevacizumab

Study Arms

• Experimental: Group A
  ARFOX (Arfolitixorin and 5-FU and Oxaliplatin) and Bevacizumab
  Intervention: Drug: Arfolitixorin
• Active Comparator: Group B
  mFOLFOX-6 (Leucovorin and 5-FU and Oxaliplatin) and Bevacizumab
  Intervention: Drug: Leucovorin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 20, 2018): 440
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2023
• Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

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, 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Roger Tell, MD, PhD; +46 (0) 760 293 911; roger.tell@isofolmedical.com

• Listed Location Countries: Australia, Austria, Canada, France, Germany, Greece, Japan, Spain, Sweden, United States

Administrative Information

• NCT Number: NCT03750786
• Other Study ID Numbers: ISO-CC-007
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Isofol Medical AB
• Study Sponsor: Isofol Medical AB
• Collaborators: Not Provided

Investigators

• Principal Investigator: Josep Tabernero, Prof.; Vall d'Hebron Institute of Oncology

• PRS Account: Isofol Medical AB
• Verification Date: February 2020