Metastatic Colorectal CancerPhase 3NCT01786538
Second-line FOLFOX With or Without Regorafenib in mCRC Patients Failed to First-line Irinotecan Plus Fluoropyrimidines
A Phase 3 study testing Regorafenib/FOLFOX in people with Metastatic Colorectal Cancer, run by Asan Medical Center at 1 site in South Korea.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Regorafenib/FOLFOX
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jun 2013to May 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Major surgery or significant traumatic injury within 28 days prior to study treatment.
- Non-healing wound, ulcer, or bone fracture.
- Current evidence of significant gastrointestinal bleeding or (impending) obstruction.
- 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.
- Concomitant participation in another clinical trial.
- 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.
- Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase III Study of Oxaliplatin, Fluorouracil and Leucovorin (FOLFOX) With or Without Regorafenib in Patients With Metastatic Colorectal Cancer Progressed After First-line Irinotecan Plus Fluoropyrimidines
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.
Read the detailed description
Limited active drugs are available for the treatment of patients with metastatic colorectal cancer (mCRC) at present and upfront doublet combination of fluoropyrimidines plus either oxaliplatin or irinotecan is regarded as reference strategy for patients appropriate for intensive therapy. Before the era of targeted agents, the treatment strategies in terms of either combination or sequence of cytotoxic agents were rather simple; survival outcomes did not differ according to either the administration sequence of oxaliplatin or irinotecan, or the sequential versus combination chemotherapy in the treatment continuum. However, the treatment strategies have become more complicated in the era of targeted agents.
In case of failure to first-line oxaliplatin plus fluoropyrimidines (FOLFOX or CapeOX) with or without bevacizumab, second-line chemotherapy with FOLFIRI would be administered for treatment continuum, and more various targeted agents can be combined in these setting; bevacizumab beyond progression only in patients who have been treated with first-line bevacizumab plus FOLFOX or CapeOX (TML and BRiTE), cetuximab (only for patients with wild-type KRAS), panitumumab (only for patients with wild-type KRAS), and aflibercept (VELOUR). However, there have been a few valid targeted agents which could be combined in the second line FOLFOX or CapeOX in those progressed after first-line FOLFIRI with or without targeted agents; bevacizumab beyond progression could be a valid treatment strategy only in those received first-line bevacizumab plus FOLFIRI. Higher dose of bevacizumab (10 mg/kg/2-week) could be combined to FOLFOX as second-line chemotherapy; however, it is not recommended at present in terms of cost effectiveness and higher adverse events, and cetuximab plus oxaliplatin-based chemotherapy is neither recommended by current consensus. Thus, there have been unmet needs for the discovery of valid targeted agent combination for the second-line FOLFOX as above reasons.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Regorafenib/FOLFOX, Placebo/FOLFOX
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib/FOLFOXDrug
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.
Placebo/FOLFOXDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib/FOLFOX | Experimental | Not described Receives: Drug: Regorafenib/FOLFOX |
| Placebo/FOLFOX | Active comparator | Not described Receives: Drug: Placebo/FOLFOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Measured: time from randomization to disease-progression or any event (up to 1 year from the end of study treatment)
Secondary outcomes (4)
Overall survival
Measured: Time from randomization to death (up to 1 year from the end of study treatment)
Response rate
Measured: every 6 weeks, up to disease progression from study treatment
Disease-control rate
partial response + stable disease
Measured: every 6 weeks, up to disease progression from study treatment
Number of participants with adverse events
Adverse events will be monitored according to the NCI-CTCAE version 4.0.
Measured: Every cycle (every 2 weeks) till the end of study treatment (because of disease progression or any event, up to 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2013 (estimated)
- Study startJun 2013
- Primary completionMay 2016 (estimated)
- Study completionMay 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tae Won Kim, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01786538
- Sponsor's protocol ID
- Regorafenib/FOLFOX
- Status last verified
- Mar 2013
- First submitted
- 4 Feb 2013
- Last updated
- 13 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase III Study of Oxaliplatin, Fluorouracil and Leucovorin (FOLFOX) With or Without Regorafenib in Patients With Metastatic Colorectal Cancer Progressed After First-line Irinotecan Plus Fluoropyrimidines
- ClinicalTrials.gov ID
- NCT01786538
- Acronym / sponsor ID
- Regorafenib/FOLFOX
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- May 2016 (estimated)
- Study completion
- May 2017 (estimated)
- First posted
- 8 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Limited active drugs are available for the treatment of patients with metastatic colorectal cancer (mCRC) at present and upfront doublet combination of fluoropyrimidines plus either oxaliplatin or irinotecan is regarded as reference strategy for patients appropriate for intensive therapy. Before the era of targeted agents, the treatment strategies in terms of either combination or sequence of cytotoxic agents were rather simple; survival outcomes did not differ according to either the administration sequence of oxaliplatin or irinotecan, or the sequential versus combination chemotherapy in the treatment continuum. However, the treatment strategies have become more complicated in the era of targeted agents.
In case of failure to first-line oxaliplatin plus fluoropyrimidines (FOLFOX or CapeOX) with or without bevacizumab, second-line chemotherapy with FOLFIRI would be administered for treatment continuum, and more various targeted agents can be combined in these setting; bevacizumab beyond progression only in patients who have been treated with first-line bevacizumab plus FOLFOX or CapeOX (TML and BRiTE), cetuximab (only for patients with wild-type KRAS), panitumumab (only for patients with wild-type KRAS), and aflibercept (VELOUR). However, there have been a few valid targeted agents which could be combined in the second line FOLFOX or CapeOX in those progressed after first-line FOLFIRI with or without targeted agents; bevacizumab beyond progression could be a valid treatment strategy only in those received first-line bevacizumab plus FOLFIRI. Higher dose of bevacizumab (10 mg/kg/2-week) could be combined to FOLFOX as second-line chemotherapy; however, it is not recommended at present in terms of cost effectiveness and higher adverse events, and cetuximab plus oxaliplatin-based chemotherapy is neither recommended by current consensus. Thus, there have been unmet needs for the discovery of valid targeted agent combination for the second-line FOLFOX as above reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regorafenib/FOLFOX | Experimental | Drug: Regorafenib/FOLFOX |
| Placebo/FOLFOX | Active comparator | Drug: Placebo/FOLFOX |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Regorafenib/FOLFOXFOLFOX 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. | Drug | Regorafenib/FOLFOX |
| Placebo/FOLFOXFOLFOX 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. | Drug | Placebo/FOLFOX |
Primary outcome
Progression-free survival
Time frame: time from randomization to disease-progression or any event (up to 1 year from the end of study treatment)
4 secondary outcomes
Overall survival
Time frame: Time from randomization to death (up to 1 year from the end of study treatment)
Response rate
Time frame: every 6 weeks, up to disease progression from study treatment
Disease-control rate
Time frame: every 6 weeks, up to disease progression from study treatment
Number of participants with adverse events
Time frame: Every cycle (every 2 weeks) till the end of study treatment (because of disease progression or any event, up to 1 year)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Regorafenib/FOLFOX in people with Metastatic Colorectal Cancer, run by Asan Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: time from randomization to disease-progression or any event (up to 1 year from the end of study treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2013.