Back to results

Avastin in Combination With Chemotherapy for RAS Mutant Unresectable Colorectal Liver-limited Metastases

Primary Purpose

Colorectal Neoplasms

Status

Completed

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

avastin

mFOLFOX6

About this trial

This is an interventional treatment trial for Colorectal Neoplasms focused on measuring colorectal neoplasms, liver metastasis, chemotherapy, avastin

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
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.

Exclusion Criteria:

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
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.

Sites / Locations

Zhongshan Hospital, Fudan University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ARM A

ARM B

Arm Description

patients received avastin in combination with mFOLFOX6

Patients received mFOLFOX6 alone

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

tumor response

Full Information

NCT ID

NCT01972490

First Posted

September 23, 2013

Last Updated

December 15, 2019

Sponsor

Xu jianmin

1. Study Identification

Unique Protocol Identification Number

NCT01972490

Brief Title

Avastin in Combination With Chemotherapy for RAS Mutant Unresectable Colorectal Liver-limited Metastases

Official Title

Study of Avastin in Combination With Chemotherapy for the First Line Treatment of RAS Mutant Unresectable Colorectal Liver-limited Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

October 2013 (Actual)

Primary Completion Date

December 2017 (Actual)

Study Completion Date

June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Xu jianmin

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Neoplasms

Keywords

colorectal neoplasms, liver metastasis, chemotherapy, avastin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

241 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ARM A

Arm Type

Experimental

Arm Description

patients received avastin in combination with mFOLFOX6

Arm Title

ARM B

Arm Type

Active Comparator

Arm Description

Patients received mFOLFOX6 alone

Intervention Type

Drug

Intervention Name(s)

avastin

Other Intervention Name(s)

Bevacizumab

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

mFOLFOX6

Intervention Description

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)

Primary Outcome Measure Information:

Title

the rate of patients converted to resection for liver metastases

Description

Time Frame

3 years

Secondary Outcome Measure Information:

Title

progression free survival

Description

Time Frame

3 years

Title

overall survival

Description

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.

Time Frame

3 years

Title

tumor response

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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. Exclusion Criteria: 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 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.

Facility Information:

Facility Name

Zhongshan Hospital, Fudan University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200000

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

32749938

Citation

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.

Results Reference

derived

Learn more about this trial

Avastin in Combination With Chemotherapy for RAS Mutant Unresectable Colorectal Liver-limited Metastases

We'll reach out to this number within 24 hrs