Overview

Second-line FOLFOX With or Without Regorafenib in mCRC Patients Failed to First-line Irinotecan Plus Fluoropyrimidines

Status:
Withdrawn
Trial end date:
2017-05-01
Target enrollment:
0
Participant gender:
All
Summary
Regorafenib has been proved to improved survival in patients with metastatic colorectal cancer who have been failed to all of known standard chemotherapy (The CORRECT study). The phase Ib study of regorafenib plus FOLFOX or FOLFIRI was performed and the dose of regorafenib was fixed; 160 mg/day on days 4 to 10 (7 days per cycle when combined with FOLFOX or FOLFIRI). Regorafenib plus FOLFOX as second-line chemotherapy in mCRC patients who progressed after first-line irinotecan-based chemotherapy has not been studied yet, and because there have been unmet needs for the discovery of valid targeted agent combination for the second-line FOLFOX as above reasons, the investigators planned this study of regorafenib plus FOLFOX as second-line chemotherapy in mCRC patients who progressed after first-line irinotecan-based chemotherapy.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Asan Medical Center
Treatments:
Fluorouracil
Irinotecan
Leucovorin
Oxaliplatin
Criteria
Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum.

2. Progressed during or within 6 months of first-line irinotecan plus fluoropyrimidines
with or without targeted agents (bevacizumab or cetuximab).

3. Measurable or evaluable lesion(s) by RECIST 1.1.

4. Unresectable metastatic disease.

5. Age over 20 years old.

6. ECOG performance status of 1 or lower.

7. Adequate organ functions. A. Bone marrow function: ANC ≥ 1,500/mm3, platelet ≥
100,000/mm3 B. Hepatic functions: bilirubin ≤ 1.5 X ULN, AST/ALT ≤ 2.5 X ULN (≤ 5 X
ULN in cases of liver metastasis) C. Renal functions: serum Cr ≤ 1.5 X ULN or
calculated CCr (Cockroft) ≥ 60 ml/min

8. Be willing and able to comply with the protocol for the duration of the study.

9. Give written informed consent prior to study-specific screening procedures, with the
understanding that the patient has the right to withdraw the study at any time,
without prejudice.

10. Women of childbearing potential and men must agree to use adequate contraception since
signing of the IC form until at least 8 weeks after the last study drug
administration.

Exclusion Criteria:

1. Prior treatment of regorafenib.

2. Prior exposure to oxaliplatin as metastatic setting is not allowed in any case;
however, prior exposure to oxaliplatin as (neo)adjuvant chemo(radio)therapy is allowed
if progressed after 12 months from the date of completion of oxaliplatin-containing
(neo)adjuvant treatment.

3. Concurrent or previous history of another primary cancer within 3 years prior to
randomisation except for curatively treated cervical cancer in situ, non-melanomatous
skin cancer, superficial bladder cancer (pTis and pT1) and curatively treated thyroid
cancer of any stage. Concurrent, histologically confirmed, unresected thyroid cancer
without distant metastasis could be allowed with the agreement of the chief principal
investigator.

4. Uncontrolled CNS metastases.

5. Prior radiation therapy would be permitted, but non-radiated evaluable lesions should
be present at study entry.

6. Radiation therapy during chemotherapy is not permitted, but if the local investigator
decides that radiation therapy should be given during study treatments, he should be
convinced that there is no evidence of disease progression with agreement of the chief
principal investigator. Radiation therapy during the chemotherapy-free interval
between 1st and 2nd line chemotherapy is permitted.

7. Uncontrolled hypertension (>150/100 mmHg) despite of optimal management;
anti-hypertensive drugs for BP lowering before study entry would be permitted.

8. Congestive heart failure ≥ New York Heart Association (NYHA) class 2.

9. Unstable angina, new-onset angina within 3 months, or history of myocardial infarction
within 6 months before the study entry.

10. Arterial or venous thromboembolism within 6 months.

11. Serious concurrent infections or non-malignant illness.

12. Liver cirrhosis ≥ Child-Pugh class B.

13. Prior unanticipated severe toxicity to fluoropyrimidines, or known dihydropyrimidine
dehydrogenase (DPD) deficiency.

14. Prior hypersensitivity to oxaliplatin (grade ≥ 2).

15. Peripheral neuropathy of grade ≥ 2.

16. Major surgery or significant traumatic injury within 28 days prior to study treatment.

17. Non-healing wound, ulcer, or bone fracture.

18. Current evidence of significant gastrointestinal bleeding or (impending) obstruction.

19. Proteinuria ≥ 3+ in the routine urinalysis; in this case, the total protein in the
24-hour urine collection should be measured, and the accrual is permitted if total
protein < 3.5 g/day.

20. Concomitant participation in another clinical trial.

21. Pregnant of breast-feeding subjects. Women of child-bearing potential must have
pregnancy test within 7 days and a negative result must be documented before start of
study treatment.

22. Substance abuse, medical, psychological or social conditions that may interfere with
the subject's participation in the study or evaluation of the study results.