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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)

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ClinicalTrials.gov Identifier: NCT03750786
Recruitment Status : Recruiting
First Posted : November 23, 2018
Last Update Posted : March 18, 2021
Sponsor:
Information provided by (Responsible Party):
Isofol Medical AB

Tracking Information
First Submitted Date  ICMJE November 19, 2018
First Posted Date  ICMJE November 23, 2018
Last Update Posted Date March 18, 2021
Actual Study Start Date  ICMJE December 18, 2018
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Colo-rectal Cancer
Intervention  ICMJE
  • Drug: Arfolitixorin
    Arfolitixorin and 5-FU and Oxaliplatin and Bevacizumab
  • Drug: Leucovorin
    Leucovorin and 5-FU and Oxaliplatin and Bevacizumab
Study Arms  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2018)
440
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2023
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Roger Tell, MD, PhD +46 (0) 760 293 911 roger.tell@isofolmedical.com
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   France,   Germany,   Greece,   Japan,   Spain,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03750786
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Isofol Medical AB
Study Sponsor  ICMJE Isofol Medical AB
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Josep Tabernero, Prof. Vall d'Hebron Institute of Oncology
PRS Account Isofol Medical AB
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP