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

NCT01786538 | Withdrawn Phase 3 DMC

• 1 other identifier: Regorafenib/FOLFOX
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  time from randomization to disease-progression or any event (up to 1 year from the end of study treatment)

Secondary Outcomes (4)

• Overall survival

  Time from randomization to death (up to 1 year from the end of study treatment)

• Response rate

  every 6 weeks, up to disease progression from study treatment

• Disease-control rate

  every 6 weeks, up to disease progression from study treatment

• Number of participants with adverse events

  Every cycle (every 2 weeks) till the end of study treatment (because of disease progression or any event, up to 1 year)

Study Arms (2)

Regorafenib/FOLFOX

EXPERIMENTAL

Drug: Regorafenib/FOLFOX

Placebo/FOLFOX

ACTIVE COMPARATOR

Drug: Placebo/FOLFOX

Interventions

Regorafenib/FOLFOX DRUG

FOLFOX consisted of oxaliplatin 85 mg/m2 on D1, leucovorin 400 mg/m2 on D1, 5-fluorouracil 400 mg/m2 intravenous bolus on D1 and 5-fluorouracil 1200 mg/m2/day continuous infusion on D1-2 (2400 mg/m2 for 46 hours). Regorafenib will be administered 160 mg/day given orally on D4-10 (7 days per each cycle of FOLFOX). Treatment will be repeated every 2 weeks and continued until disease progression, unacceptable toxicity or the patient's refusal.

Regorafenib/FOLFOX

Placebo/FOLFOX DRUG

FOLFOX consisted of oxaliplatin 85 mg/m2 on D1, leucovorin 400 mg/m2 on D1, 5-fluorouracil 400 mg/m2 intravenous bolus on D1 and 5-fluorouracil 1200 mg/m2/day continuous infusion on D1-2 (2400 mg/m2 for 46 hours). Placebo will be administered 160 mg/day given orally on D4-10 (7 days per each cycle of FOLFOX). Treatment will be repeated every 2 weeks and continued until disease progression, unacceptable toxicity or the patient's refusal.

Placebo/FOLFOX

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum.
• Progressed during or within 6 months of first-line irinotecan plus fluoropyrimidines with or without targeted agents (bevacizumab or cetuximab).
• Measurable or evaluable lesion(s) by RECIST 1.1.
• Unresectable metastatic disease.
• Age over 20 years old.
• ECOG performance status of 1 or lower.
• 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
• Be willing and able to comply with the protocol for the duration of the study.
• 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.
• 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.

You may not qualify if:

• Prior treatment of regorafenib.
• 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.
• 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.
• Uncontrolled CNS metastases.
• Prior radiation therapy would be permitted, but non-radiated evaluable lesions should be present at study entry.
• 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.
• Uncontrolled hypertension (\>150/100 mmHg) despite of optimal management; anti-hypertensive drugs for BP lowering before study entry would be permitted.
• Congestive heart failure ≥ New York Heart Association (NYHA) class 2.
• Unstable angina, new-onset angina within 3 months, or history of myocardial infarction within 6 months before the study entry.
• Arterial or venous thromboembolism within 6 months.
• Serious concurrent infections or non-malignant illness.
• Liver cirrhosis ≥ Child-Pugh class B.
• Prior unanticipated severe toxicity to fluoropyrimidines, or known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Prior hypersensitivity to oxaliplatin (grade ≥ 2).
• Peripheral neuropathy of grade ≥ 2.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, Songpa-gu, 138736, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 4, 2013
• First Posted: February 8, 2013
• Study Start: June 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2017
• Last Updated: March 13, 2013

Record last verified: 2013-03

Locations

KR (1)