Colorectal CancerPhase 4NCT01695772
A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
A Phase 4 study testing 5-FU based doublet chemotherapy and bevacizumab in people with Colorectal Cancer, run by Hoffmann-La Roche at 7 sites in China.
Trial summary
This open-label, single arm, multicenter study evaluated the resection rate in participants with colorectal cancer and previously untreated unresectable liver-only metastases after adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- 5-FU based doublet chemotherapy and bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 7 sitesChina
- Study dates
- 16 Oct 2012to 12 May 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult Chinese participants, 18-75 years of age
- Histologically confirmed adenocarcinoma in colon or rectum with primary lesion surgically removed
- Previously untreated unresectable liver-only metastases
- Liver lesions determined to be unresectable by multidisciplinary team (MDT, consisting of experienced hepatic surgeons, medical oncologist and radiologist).
- No previous treatment against liver metastases, including chemotherapy, surgery, radiotherapy, Transarterial chemoembolisation therapy (TACE) and target therapy
- Adequate hematological, renal and hepatic function
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Life expectancy greater than (>) 3 months
Who cannot join
- The relapse has occurred within 6 months of completion of the adjuvant treatment
- Expected impossible to achieve complete resection (R0 resection) and/or gain 30% residual liver volume even with responsive neoadjuvant therapy
- Participant cannot tolerate the surgery
- Other malignancies in the past 5 years, except for curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
- Any extrahepatic metastases and/or recurrence of the primary tumor
- Any residual toxicity from previous chemotherapy (except alopecia) of National Cancer Institute Common Toxicity Criteria (NCI CTC) v.4.0 grade 2
Show all 12Show fewer
- Hypertension crisis or encephalopathy
- Pregnant or lactating women
- Clinically significant cardiovascular disease
- Evidence of bleeding diathesis or coagulopathy
- Current or recent (within 10 days of study drug initiation) use of full dose of aspirin, clopidrogel or warfarin
- History or evidence of Central Nervous System (CNS) disease (for example, primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
China7 sites
Beijing Cancer Hospital
Beijing, 100142
Sun Yet-sen University Cancer Center
Guangzhou, 510060
The Second Affiliated Hospital of Zhejiang University College
Hangzhou, 310009
The 2nd Affiliated Hospital of Harbin Medical University
Harbin, 150001
Zhongshan Hospital Fudan University
Shanghai, 200032
Liaoning cancer Hospital & Institute
Shenyang, 110042
Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology
Wuhan, 430022
About this study
Official title: A Multi-Center, Single-Arm, Pilot Study of 5-FU Based Doublet Chemotherapy Plus Bevacizumab as Neoadjuvant Therapy for Patients With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
This open-label, single arm, multicenter study evaluated the resection rate in participants with colorectal cancer and previously untreated unresectable liver-only metastases after adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting. Participants receive standard 5-FU based chemotherapy plus Avastin bevacizumab 5 milligrams per kilogram (mg/kg) every 2 weeks for a maximum of 12 cycles combined pre- and postoperatively, unless they experienced progressive disease or unacceptable toxicity.
- Conditions
- Colorectal Cancer
- Being tested
- 5-FU based doublet chemotherapy, 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.
5-FU based doublet chemotherapyDrug
Standard 5-FU based doublet chemotherapy. Protocol did not specify any particular chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels.
bevacizumabDrug
Also called Avastin
5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab | Experimental | Not described Receives: Drug: 5-FU based doublet chemotherapy; Drug: bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Complete Resection (R0 Resection)
R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
Measured: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
Secondary outcomes (8)
Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)
R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
Measured: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
Percentage of Participants Achieving Objective Response
Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Measured: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Number of Participants With Disease Progression or Relapse or Death
According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions.
Measured: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Progression Free Survival (PFS)
Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS.
Measured: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18
Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis.
Measured: Months 3, 6, 9, 12, 15, and 18
Number of Participants With Disease Relapse or Death
Measured: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Disease Free Survival (DFS)
Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab.
Measured: Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years)
Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12
Measured: Months 3, 6, 9, and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2012 (estimated)
- Study start16 Oct 2012
- Primary completion4 Apr 2015
- Study completion12 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01695772
- Sponsor's protocol ID
- ML28419
- Status last verified
- May 2017
- First submitted
- 27 Sep 2012
- Last updated
- 9 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Single-Arm, Pilot Study of 5-FU Based Doublet Chemotherapy Plus Bevacizumab as Neoadjuvant Therapy for Patients With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01695772
- Acronym / sponsor ID
- ML28419
- Conditions
- Colorectal Cancer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 16 Oct 2012 (actual)
- Primary completion
- 4 Apr 2015 (actual)
- Study completion
- 12 May 2016 (actual)
- First posted
- 28 Sep 2012 (estimated)
- Results
- Posted 28 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This open-label, single arm, multicenter study evaluated the resection rate in participants with colorectal cancer and previously untreated unresectable liver-only metastases after adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting. Participants receive standard 5-FU based chemotherapy plus Avastin bevacizumab 5 milligrams per kilogram (mg/kg) every 2 weeks for a maximum of 12 cycles combined pre- and postoperatively, unless they experienced progressive disease or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab | Experimental | Drug: 5-FU based doublet chemotherapy, Drug: bevacizumab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult Chinese participants, 18-75 years of age
- Histologically confirmed adenocarcinoma in colon or rectum with primary lesion surgically removed
- Previously untreated unresectable liver-only metastases
- Liver lesions determined to be unresectable by multidisciplinary team (MDT, consisting of experienced hepatic surgeons, medical oncologist and radiologist).
- No previous treatment against liver metastases, including chemotherapy, surgery, radiotherapy, Transarterial chemoembolisation therapy (TACE) and target therapy
Key exclusion criteria (12 listed)
- The relapse has occurred within 6 months of completion of the adjuvant treatment
- Expected impossible to achieve complete resection (R0 resection) and/or gain 30% residual liver volume even with responsive neoadjuvant therapy
- Participant cannot tolerate the surgery
- Other malignancies in the past 5 years, except for curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
- Any extrahepatic metastases and/or recurrence of the primary tumor
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 |
|---|---|---|
| 5-FU based doublet chemotherapyStandard 5-FU based doublet chemotherapy. Protocol did not specify any particular chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels. | Drug | Bevacizumab |
| bevacizumabAlso: Avastin5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively | Drug | Bevacizumab |
Primary outcome
Percentage of Participants Achieving Complete Resection (R0 Resection)
Time frame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
8 secondary outcomes
Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)
Time frame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
Percentage of Participants Achieving Objective Response
Time frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Number of Participants With Disease Progression or Relapse or Death
Time frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Progression Free Survival (PFS)
Time frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18
Time frame: Months 3, 6, 9, 12, 15, and 18
Number of Participants With Disease Relapse or Death
Time frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
Disease Free Survival (DFS)
Time frame: Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years)
Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12
Time frame: Months 3, 6, 9, and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Clinical Trials study director
Hoffmann-La Roche
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 5-FU based doublet chemotherapy and bevacizumab in people with Colorectal Cancer, run by Hoffmann-La Roche at 7 sites in China.
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 8 inclusion and 12 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: finished, as of the sponsor's last update on 9 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants Achieving Complete Resection (R0 Resection) (time frame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)). 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 9 Jun 2017.