Colorectal NeoplasmsPhase 4NCT01972490
Avastin in Combination With Chemotherapy for RAS Mutant Unresectable Colorectal Liver-limited Metastases
A Phase 4 study testing avastin and mFOLFOX6 in people with Colorectal Neoplasms, run by Xu jianmin at 1 site in China.
Trial summary
In this study, the investigators assessed the effect of avastin in combination with chemotherapy in the treatment of RAS mutant-type, unresectable colorectal liver-limited metastases Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- avastin and mFOLFOX6
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 241 participants
- Where
- 1 siteChina
- Study dates
- Oct 2013to Jun 2019
- Phase
- Phase 4
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and ≤ 75 years;
- Primary tumour was histologically confirmed colorectal adenocarcinoma;
- Together with clinical or radiological evidence of first occurrence of non-resectable liver-only metastases
- With evidence of tumor RAS gene mutant status;
- With at least one measurable tumor.
- Performance status (ECOG) 0~1
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- A life expectancy of ≥ 3 months
- Adequate hematological function: Neutrophils≥1.5 x109/l and platelet count≥100 x109/l; Hb ≥9g/dl (within 1 week prior to randomization)
- Adequate hepatic and renal function: Serum bilirubin≤1.5 x upper limit of normal (ULN), alkaline phosphatase ≤5x ULN, and serum transaminase (either AST or ALT) ≤ 5 x ULN(within 1 week prior to randomization);
- Written informed consent for participation in the trial.
Who cannot join
- Previous exposure to target therapy, chemotherapy, radiotherapy or intervention therapy for colorectal liver metastases.
- Known or suspected extrahepatic metastases.
- Patients with known hypersensitivity reactions to any of the components of the study treatments.
- Having previously participated in a study which included a possibility of being allocated to avastin therapy (whether or not the patient actually received avastin)
- Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months or left ventricular ejection fraction (LVEF) below the institutional range of normal
- Acute or sub-acute intestinal occlusion
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- Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding
- Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
- Known drug abuse/ alcohol abuse
- Legal incapacity or limited legal capacity
- Pre-existing peripheral neuropathy.
Trial locations and contacts
1 site in 1 country.
China1 site
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200000
About this study
Official title: Study of Avastin in Combination With Chemotherapy for the First Line Treatment of RAS Mutant Unresectable Colorectal Liver-limited Metastases
In this study, the investigators assessed the effect of avastin in combination with chemotherapy in the treatment of RAS mutant-type, unresectable colorectal liver-limited metastases
Read the detailed description
Patients will be eligible for inclusion if the patients have histologically confirmed colorectal adenocarcinoma with RAS mutant liver-confined metastases deemed non-resectable. Eligible patients will be randomly assigned to chemotherapy plus avastin (arm A) or chemotherapy alone (arm B). Treatment will continue until tumor response indicates suitability for surgery for liver metastases or until disease progression or unacceptable toxic effects. The primary endpoint is the conversion rate to radical resection for liver metastases，which will be assessed by local multidisciplinary team (includes more than three liver surgeons and one radiologist) with the use of contrast-enhanced CT or MRI after 4 cycles and then every other 4 cycles up to 12 cycles. To provide an objective assessment of changes in resectability, radiological images will be presented by a radiologist to more than 3 liver surgeons, who are blinded to the clinical data. Patients will be considered resectable if 50% or more of surgeons vote for radical resection of LM. For patients whose liver-metastases are assessed resectable, resection should be scheduled to be performed within 2~3 weeks of the last treatment cycle. Following resection, patients will be advised to continue the same therapeutic regimen until the treatments reach a sum of 12 cycles.
- Conditions
- Colorectal Neoplasms
- Being tested
- avastin, mFOLFOX6
- Keywords
- colorectal neoplasms, liver metastasis, chemotherapy, avastin
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
avastinDrug
Also called Bevacizumab
Drug: avastin On day 1 of a 14 day treatment cycle, patients received a 2-hour infusion of avastin (5mg/kg) followed by chemotherapy of mFOLFOX6 until progressive disease or unacceptable toxicity.
mFOLFOX6Drug
mFOLFOX-6 (oxaliplatin, 85mg/m2 on day 1 infused during 2 hours;LV400mg/m2 on days 1 infused during 2 hours, followed by FU 400 mg/m2 intravenous bolus then 2400 mg/m2 continuous infusion for 46 hours)
| Study group | Role | What they receive |
|---|---|---|
| ARM A | Experimental | patients received avastin in combination with mFOLFOX6 Receives: Drug: avastin; Drug: mFOLFOX6 |
| ARM B | Active comparator | Patients received mFOLFOX6 alone Receives: Drug: mFOLFOX6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
the rate of patients converted to resection for liver metastases
To explore whether avastin in combination with chemotherapy as treatment could improve the resection rate in patients with RAS mutant-type, unresectable colorectal liver-limited metastases compared with chemotherapy alone.
Measured: 3 years
Secondary outcomes (3)
progression free survival
PFS will be defined as the period from the first day of avastin treatment or chemotherapy to the date of disease progression (PD) or to death. Patients without PD who discontinued the study for any reason is censored at the last on-study tumor assessment date.or distant(i.e. metastasis) disease recurrence or death.
Measured: 3 years
overall survival
OS will be calculated from randomization to death from any cause or the date of the last follow-up, at which point the data will be censored.
Measured: 3 years
tumor response
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionDec 2017
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xu jianmin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xu jianmin, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01972490
- Sponsor's protocol ID
- ACCMCLM
- Status last verified
- Dec 2019
- First submitted
- 23 Sep 2013
- Last updated
- 17 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tang W, Ren L, Liu T, Ye Q, Wei Y, He G, Lin Q, Wang X, Wang M, Liang F, Cui Y, Xu J. Bevacizumab Plus mFOLFOX6 Versus mFOLFOX6 Alone as First-Line Treatment for RAS Mutant Unresectable Colorectal Liver-Limited Metastases: The BECOME Randomized Controlled Trial. J Clin Oncol. 2020 Sep 20;38(27):3175-3184. doi: 10.1200/JCO.20.00174. Epub 2020 Aug 4.
PubMed 32749938
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Avastin in Combination With Chemotherapy for the First Line Treatment of RAS Mutant Unresectable Colorectal Liver-limited Metastases
- ClinicalTrials.gov ID
- NCT01972490
- Acronym / sponsor ID
- ACCMCLM
- Conditions
- Colorectal Neoplasms
- Keywords
- colorectal neoplasms, liver metastasis, chemotherapy, avastin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Xu jianminUniversity, hospital or other
- Study start
- Oct 2013 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 30 Oct 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.
In this study, the investigators assessed the effect of avastin in combination with chemotherapy in the treatment of RAS mutant-type, unresectable colorectal liver-limited metastases
Detailed description
Patients will be eligible for inclusion if the patients have histologically confirmed colorectal adenocarcinoma with RAS mutant liver-confined metastases deemed non-resectable. Eligible patients will be randomly assigned to chemotherapy plus avastin (arm A) or chemotherapy alone (arm B). Treatment will continue until tumor response indicates suitability for surgery for liver metastases or until disease progression or unacceptable toxic effects. The primary endpoint is the conversion rate to radical resection for liver metastases，which will be assessed by local multidisciplinary team (includes more than three liver surgeons and one radiologist) with the use of contrast-enhanced CT or MRI after 4 cycles and then every other 4 cycles up to 12 cycles. To provide an objective assessment of changes in resectability, radiological images will be presented by a radiologist to more than 3 liver surgeons, who are blinded to the clinical data. Patients will be considered resectable if 50% or more of surgeons vote for radical resection of LM. For patients whose liver-metastases are assessed resectable, resection should be scheduled to be performed within 2~3 weeks of the last treatment cycle. Following resection, patients will be advised to continue the same therapeutic regimen until the treatments reach a sum of 12 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A | Experimental | Drug: avastin, Drug: mFOLFOX6patients received avastin in combination with mFOLFOX6 |
| ARM B | Active comparator | Drug: mFOLFOX6Patients received mFOLFOX6 alone |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 18 and ≤ 75 years;
- Primary tumour was histologically confirmed colorectal adenocarcinoma;
- Together with clinical or radiological evidence of first occurrence of non-resectable liver-only metastases
- With evidence of tumor RAS gene mutant status;
- With at least one measurable tumor.
Key exclusion criteria (11 listed)
- Previous exposure to target therapy, chemotherapy, radiotherapy or intervention therapy for colorectal liver metastases.
- Known or suspected extrahepatic metastases.
- Patients with known hypersensitivity reactions to any of the components of the study treatments.
- Having previously participated in a study which included a possibility of being allocated to avastin therapy (whether or not the patient actually received avastin)
- Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months or left ventricular ejection fraction (LVEF) below the institutional range of normal
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 |
|---|---|---|
| avastinAlso: BevacizumabDrug: avastin On day 1 of a 14 day treatment cycle, patients received a 2-hour infusion of avastin (5mg/kg) followed by chemotherapy of mFOLFOX6 until progressive disease or unacceptable toxicity. | Drug | ARM A |
| mFOLFOX6mFOLFOX-6 (oxaliplatin, 85mg/m2 on day 1 infused during 2 hours;LV400mg/m2 on days 1 infused during 2 hours, followed by FU 400 mg/m2 intravenous bolus then 2400 mg/m2 continuous infusion for 46 hours) | Drug | ARM A, ARM B |
Primary outcome
the rate of patients converted to resection for liver metastases
Time frame: 3 years
To explore whether avastin in combination with chemotherapy as treatment could improve the resection rate in patients with RAS mutant-type, unresectable colorectal liver-limited metastases compared with chemotherapy alone.
3 secondary outcomes
progression free survival
Time frame: 3 years
overall survival
Time frame: 3 years
tumor response
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Derived from this study: PubMed 32749938Tang W, Ren L, Liu T, Ye Q, Wei Y, He G, Lin Q, Wang X, Wang M, Liang F, Cui Y, Xu J. Bevacizumab Plus mFOLFOX6 Versus mFOLFOX6 Alone as First-Line Treatment for RAS Mutant Unresectable Colorectal Liver-Limited Metastases: The BECOME Randomized Controlled Trial. J Clin Oncol. 2020 Sep 20;38(27):3175-3184. doi: 10.1200/JCO.20.00174. Epub 2020 Aug 4.
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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 4 study testing avastin and mFOLFOX6 in people with Colorectal Neoplasms, run by Xu jianmin at 1 site 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 10 inclusion and 11 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 17 Dec 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
the rate of patients converted to resection for liver metastases (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01972490, which also lists 1 linked publication.
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 17 Dec 2019.