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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03750786




Registration number
NCT03750786
Ethics application status
Date submitted
19/11/2018
Date registered
23/11/2018
Date last updated
5/06/2020

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
ISO-CC-007
Universal Trial Number (UTN)
Trial acronym
AGENT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colo-rectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Arfolitixorin
Treatment: Drugs - Leucovorin

Experimental: Group A - ARFOX (Arfolitixorin and 5-FU and Oxaliplatin) and Bevacizumab

Active Comparator: Group B - mFOLFOX-6 (Leucovorin and 5-FU and Oxaliplatin) and Bevacizumab


Treatment: Drugs: Arfolitixorin
Arfolitixorin and 5-FU and Oxaliplatin and Bevacizumab

Treatment: Drugs: Leucovorin
Leucovorin and 5-FU and Oxaliplatin and Bevacizumab

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall response rate - Best ORR, defined as the best response recorded from the start of the study treatment until the end of treatment.
Timepoint [1] 0 0
Until disease progression, an average of ten months
Secondary outcome [1] 0 0
Progression free survival - PFS, defined as the time from randomization to first occurrence of tumor progression based on CT-scans/MRIs.
Timepoint [1] 0 0
Until disease progression, an average of ten months
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Until disease progression, an average of ten months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
036-10 - Border Medical Oncology Research Unit - Albury
Recruitment hospital [2] 0 0
036-02 - Chris O'Brien Lifehouse - Sydney
Recruitment hospital [3] 0 0
036-03 - Westmead Hospital - Sydney
Recruitment hospital [4] 0 0
036-08 - Tweed Hospital - Tweed Heads
Recruitment hospital [5] 0 0
036-09 - Southern Medical Day Care Center - Wollongong
Recruitment hospital [6] 0 0
036-06 - Adelaide Cancer Center - Adelaide
Recruitment hospital [7] 0 0
036-04 - Peninsula Health - Frankston Hospital - Frankston
Recruitment hospital [8] 0 0
036-01 - Western Health - Sunshine Hospital - Melbourne
Recruitment hospital [9] 0 0
036-07 - Northern Health - Epping Hospital - Melbourne
Recruitment hospital [10] 0 0
036-05 - Monash Health - Melbourne
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Sydney
Recruitment postcode(s) [4] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [5] 0 0
2500 - Wollongong
Recruitment postcode(s) [6] 0 0
5037 - Adelaide
Recruitment postcode(s) [7] 0 0
3199 - Frankston
Recruitment postcode(s) [8] 0 0
3021 - Melbourne
Recruitment postcode(s) [9] 0 0
3076 - Melbourne
Recruitment postcode(s) [10] 0 0
3168 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Montana
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Austria
State/province [20] 0 0
Klagenfurt
Country [21] 0 0
Austria
State/province [21] 0 0
Linz
Country [22] 0 0
Austria
State/province [22] 0 0
Salzburg
Country [23] 0 0
Austria
State/province [23] 0 0
Wiener Neustadt
Country [24] 0 0
Austria
State/province [24] 0 0
Wien
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
Canada
State/province [27] 0 0
Laval
Country [28] 0 0
Canada
State/province [28] 0 0
Montréal
Country [29] 0 0
Canada
State/province [29] 0 0
Ottawa
Country [30] 0 0
France
State/province [30] 0 0
Créteil
Country [31] 0 0
France
State/province [31] 0 0
Dijon
Country [32] 0 0
France
State/province [32] 0 0
Levallois-Perret
Country [33] 0 0
France
State/province [33] 0 0
Lyon
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France
State/province [34] 0 0
Marseille
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France
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Paris
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France
State/province [36] 0 0
Périgueux
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France
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Strasbourg
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Frankfurt am Main
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Germany
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Hamburg
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Germany
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Kassel
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Germany
State/province [43] 0 0
Kiel
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Germany
State/province [44] 0 0
Leipzig
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Germany
State/province [45] 0 0
Marburg
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Germany
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Merseburg
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Germany
State/province [47] 0 0
München
Country [48] 0 0
Germany
State/province [48] 0 0
Nürnberg
Country [49] 0 0
Germany
State/province [49] 0 0
Weiden
Country [50] 0 0
Greece
State/province [50] 0 0
Athens
Country [51] 0 0
Greece
State/province [51] 0 0
Athen
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Greece
State/province [52] 0 0
Larissa
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Japan
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Chiba
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Japan
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Shizuoka
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Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
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Córdoba
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Spain
State/province [57] 0 0
Madrid
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Spain
State/province [58] 0 0
Málaga
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Spain
State/province [59] 0 0
Sevilla
Country [60] 0 0
Sweden
State/province [60] 0 0
Stockholm
Country [61] 0 0
Sweden
State/province [61] 0 0
Uppsala

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Isofol Medical AB
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03750786
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Josep Tabernero, Prof.
Address 0 0
Vall d'Hebron Institute of Oncology
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Roger Tell, MD, PhD
Address 0 0
Country 0 0
Phone 0 0
+46 (0) 760 293 911
Fax 0 0
Email 0 0
roger.tell@isofolmedical.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03750786