Colorectal CancerPhase 2CBLNCT03711240
The Efficacy of Bevacizumab Combined With m-FOLFOXIRI in Borderline Resectable Colorectal Liver Metastases
A Phase 2 study testing bevacizumab, Oxaliplatin and Irinotecan in people with Colorectal Cancer, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
This single-arm study will evaluate the resection rate of liver metastases in patients with metastatic colorectal cancer and borderline unresectable liver metastases receiving treatment with bevacizumab in combination with modified-FOLFOXIRI as first line treatment. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- bevacizumab, Oxaliplatin and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteTaiwan
- Study dates
- 8 Jan 2019to 30 Oct 2020
- Phase
- Phase 2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven diagnosis of colorectal cancer.
- Borderline resectable liver metastases of colorectal cancer considered to have poor-risk disease not deemed to be suitable for upfront resection if they had one or more of the following features assessed by a local multidisciplinary team: more than four metastases, any liver lesion with diameter >5 cm, location and distribution of metastatic disease within the liver unsuitable for resection with clear margins (e.g. involvement of both lobes of liver, invasion of intrahepatic vascular structures), extent of liver involvement precluding resection with adequate post-resection residual liver parenchyma volume for viable liver function in the immediate postoperative period, and inability to retain adequate vascular inflow and outflow to maintain viable liver function.
- At least one measurable lesion according to RECIST criteria.
- Age 20-75 years.
- ECOG performance < 1 if age < 70 years, ECOG PS = 0 if age = 70-75 years.
- Life expectancy of at least 12 weeks.
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- Neutrophils ≥1.5 x 109/L, Platelets≥ 100 x 109/L, Hgb ≥10 g/dl.
- Total bilirubin ≤1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤5 x UNL, alkaline phosphatase ≤5 x UNL.
- Serum creatinine≤ 1.5 x UNL.
- Patients discovered to have proteinuria on urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein/24 hr.
- Written informed consent.
Who cannot join
- Prior neoadjuvant or adjuvant chemotherapy completed <6 months.
- Prior chemotherapy for metastatic disease.
- Any extrahepatic metastases.
- History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
- Serious, non-healing wound, ulcer, or bone fracture.
- Evidence of bleeding diathesis or coagulopathy.
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- Uncontrolled hypertension.
- Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
- Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes.
- Chronic daily treatment with aspirin .
- Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications.
- Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of sin basal cell carcinoma or cervical cancer in situ.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
- Other severe systemic diseases without stable medical control.
- Pregnant or lactating women.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Cheng-Kung University Hospital
Tainan
Jean Yang
Shang Hung Chen
About this study
Official title: Study to Investigate Efficacy of Bevacizumab Combined With Modified-FOLFOXIRI in Patients With Borderline Resectable Colorectal Liver Metastases
This single-arm study will evaluate the resection rate of liver metastases in patients with metastatic colorectal cancer and borderline unresectable liver metastases receiving treatment with bevacizumab in combination with modified-FOLFOXIRI as first line treatment. Patients will receive bevacizumab (5 mg/kg) plus modified-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2400 mg/m2 as a 46-h continuous infusion) every 14 days as neoadjuvant chemotherapy regimen. This study treatment will continue until surgery, disease progression, unacceptable toxicity, or patient refusal.
Read the detailed description
This is a phase II study to investigate the efficacy of biweekly bevacizumab in combination with modified-FOLFOXIRI regimen, as first-line chemotherapy in patients with borderline resectable colorectal liver metastases. Borderline resectable liver metastases are considered to have poor-risk diseases infeasible for upfront resection, but own the potential for resection after down-staging. The primary purpose of the study is to determine the resection rate of liver metastases in patients receiving this combination regimen. The secondary objectives are to determine the response rate, progression free survival, overall survival, and safety profiles.
Eligible patients will receive a triplet chemotherapy consisting of bevacizumab (5 mg/kg) plus modified-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2400 mg/m2 as a 46-h continuous infusion) every 14 days as a cycle. Resectability of primary tumor and liver metastases will be assessed after five cycles of combination treatment with feasible image exams. Patients with progressive disease will be discontinued in this study. For patients feasible for tumor resection, the modified triplet chemotherapy without bevacizumab combination will be continued for one other cycle for patients before surgery. If patients don't reach both the feasibility of tumor resection and progressive disease, another four cycles of bevacizumab combined with modified-FOLFOXIRI could be continued by investigator's judgement. Reassessment of resectability for primary tumor and liver metastases will be conducted using feasible image exams after a total of 9 cycles of combination treatment in these patients. Similarly, the triplet chemotherapy without bevacizumab combination will be continued for the other one cycle before surgery for these patients feasible for tumor resection after reassessment. Bevacizumab should be stopped at least 4 weeks before the planned day of surgery. Short-course radiotherapy will be allowed before surgery for patients with rectal cancer. All patients will be discontinued in this study after tumor resection. Treatment will also be discontinued if the patient requests or the investigator decides that therapy should be withdrawn. Further tumor treatment after treatment discontinuation will be decided based on investigator's judgement with the best knowledge.
- Conditions
- Colorectal Cancer
- Being tested
- bevacizumab, Oxaliplatin, Irinotecan, Leucovorin, 5-FU
- Keywords
- colorectal liver metastases, FOLFOXIRI, bevacizumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabDrug
5mg/kg iv day 1 every 2 weeks
OxaliplatinDrug
85mg/m2 2-hour iv infusion, day 1 every 2 weeks
IrinotecanDrug
150mg/m2 1.5-hour iv infusion, day 1 every 2 weeks
LeucovorinDrug
200mg/m2 2-hour iv infusion, day 1 every 2 weeks
5-FUDrug
2400mg/m2 46-hour continuous iv infusion, day 1 every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| bevacizumab+mFOLFOXIRI | Experimental | Not described Receives: Drug: bevacizumab; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resection rate of liver metastases
The percentage of the number of subjects with R0 and R1 resection after treatment.
Measured: 6 months
Secondary outcomes (4)
Tumor response rate
The percentage of the number of subjects with tumor response after combination treatment evaluated using the RECIST criteria version 1.1.
Measured: 6 months
Progression free survival
Time duration measured from the day of registration until the first observation of disease progression based on image exam findings or investigator clinical judgement.
Measured: 5 years
Overall survival
Time duration between the day of registration and the date of death or the last date the patient was known to be alive.
Measured: 5 years
Percentage of adverse effects related to combination treatment
The percentage of subjects with adverse effects related to combination treatment evaluated using the CTCAE criteria version 4.03.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2018
- Study start8 Jan 2019
- Primary completion30 Oct 2020 (estimated)
- Study completion30 Oct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shang Hung Chen, Principal investigator, National Health Research Institutes, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03711240
- Sponsor's protocol ID
- IIT-10
- Acronym
- CBL
- Status last verified
- Mar 2019
- First submitted
- 12 Oct 2018
- Last updated
- 13 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Investigate Efficacy of Bevacizumab Combined With Modified-FOLFOXIRI in Patients With Borderline Resectable Colorectal Liver Metastases
- ClinicalTrials.gov ID
- NCT03711240
- Acronym / sponsor ID
- CBL / IIT-10
- Conditions
- Colorectal Cancer
- Keywords
- colorectal liver metastases, FOLFOXIRI, bevacizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- 8 Jan 2019 (actual)
- Primary completion
- 30 Oct 2020 (estimated)
- Study completion
- 30 Oct 2020 (estimated)
- First posted
- 18 Oct 2018 (actual)
- 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.
This single-arm study will evaluate the resection rate of liver metastases in patients with metastatic colorectal cancer and borderline unresectable liver metastases receiving treatment with bevacizumab in combination with modified-FOLFOXIRI as first line treatment. Patients will receive bevacizumab (5 mg/kg) plus modified-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2400 mg/m2 as a 46-h continuous infusion) every 14 days as neoadjuvant chemotherapy regimen. This study treatment will continue until surgery, disease progression, unacceptable toxicity, or patient refusal.
Detailed description
This is a phase II study to investigate the efficacy of biweekly bevacizumab in combination with modified-FOLFOXIRI regimen, as first-line chemotherapy in patients with borderline resectable colorectal liver metastases. Borderline resectable liver metastases are considered to have poor-risk diseases infeasible for upfront resection, but own the potential for resection after down-staging. The primary purpose of the study is to determine the resection rate of liver metastases in patients receiving this combination regimen. The secondary objectives are to determine the response rate, progression free survival, overall survival, and safety profiles.
Eligible patients will receive a triplet chemotherapy consisting of bevacizumab (5 mg/kg) plus modified-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2400 mg/m2 as a 46-h continuous infusion) every 14 days as a cycle. Resectability of primary tumor and liver metastases will be assessed after five cycles of combination treatment with feasible image exams. Patients with progressive disease will be discontinued in this study. For patients feasible for tumor resection, the modified triplet chemotherapy without bevacizumab combination will be continued for one other cycle for patients before surgery. If patients don't reach both the feasibility of tumor resection and progressive disease, another four cycles of bevacizumab combined with modified-FOLFOXIRI could be continued by investigator's judgement. Reassessment of resectability for primary tumor and liver metastases will be conducted using feasible image exams after a total of 9 cycles of combination treatment in these patients. Similarly, the triplet chemotherapy without bevacizumab combination will be continued for the other one cycle before surgery for these patients feasible for tumor resection after reassessment. Bevacizumab should be stopped at least 4 weeks before the planned day of surgery. Short-course radiotherapy will be allowed before surgery for patients with rectal cancer. All patients will be discontinued in this study after tumor resection. Treatment will also be discontinued if the patient requests or the investigator decides that therapy should be withdrawn. Further tumor treatment after treatment discontinuation will be decided based on investigator's judgement with the best knowledge.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bevacizumab+mFOLFOXIRI | Experimental | Drug: bevacizumab, Drug: Oxaliplatin, Drug: Irinotecan, Drug: Leucovorin, Drug: 5-FU |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically proven diagnosis of colorectal cancer.
- Borderline resectable liver metastases of colorectal cancer considered to have poor-risk disease not deemed to be suitable for upfront resection if they had one or more of the following features assessed by a local multidisciplinary team: more than four metastases, any liver lesion with diameter >5 cm, location and distribution of metastatic disease within the liver unsuitable for resection with clear margins (e.g. involvement of both lobes of liver, invasion of intrahepatic vascular structures), extent of liver involvement precluding resection with adequate post-resection residual liver parenchyma volume for viable liver function in the immediate postoperative period, and inability to retain adequate vascular inflow and outflow to maintain viable liver function.
- At least one measurable lesion according to RECIST criteria.
- Age 20-75 years.
- ECOG performance < 1 if age < 70 years, ECOG PS = 0 if age = 70-75 years.
Key exclusion criteria (15 listed)
- Prior neoadjuvant or adjuvant chemotherapy completed <6 months.
- Prior chemotherapy for metastatic disease.
- Any extrahepatic metastases.
- History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
- Serious, non-healing wound, ulcer, or bone fracture.
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 |
|---|---|---|
| bevacizumab5mg/kg iv day 1 every 2 weeks | Drug | bevacizumab+mFOLFOXIRI |
| Oxaliplatin85mg/m2 2-hour iv infusion, day 1 every 2 weeks | Drug | bevacizumab+mFOLFOXIRI |
| Irinotecan150mg/m2 1.5-hour iv infusion, day 1 every 2 weeks | Drug | bevacizumab+mFOLFOXIRI |
| Leucovorin200mg/m2 2-hour iv infusion, day 1 every 2 weeks | Drug | bevacizumab+mFOLFOXIRI |
| 5-FU2400mg/m2 46-hour continuous iv infusion, day 1 every 2 weeks | Drug | bevacizumab+mFOLFOXIRI |
Primary outcome
Resection rate of liver metastases
Time frame: 6 months
The percentage of the number of subjects with R0 and R1 resection after treatment.
4 secondary outcomes
Tumor response rate
Time frame: 6 months
Progression free survival
Time frame: 5 years
Overall survival
Time frame: 5 years
Percentage of adverse effects related to combination treatment
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2019.
- Individual participant dataSharing planned: No
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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.
Shang Hung Chen principal investigator
National Health Research Institutes, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab, Oxaliplatin and Irinotecan in people with Colorectal Cancer, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
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 11 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 13 Mar 2019. 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 Taiwan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean Yang (+886-6-7000123 ext. 65105, JeanYang@nhri.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resection rate of liver metastases (time frame: 6 months). 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 2019.