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

Colorectal Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01972490
• Other study ID #: ACCMCLM
• Status: Completed
• Phase: Phase 4
• Start date: October 2013
• Est. completion date: June 2019

Study information

• Verified date: December 2019
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 241
• Est. completion date: June 2019
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age = 18 and = 75 years;

2. Primary tumour was histologically confirmed colorectal adenocarcinoma;

3. Together with clinical or radiological evidence of first occurrence of non-resectable liver-only metastases

4. With evidence of tumor RAS gene mutant status;

5. With at least one measurable tumor.

6. Performance status (ECOG) 0~1

7. A life expectancy of = 3 months

8. Adequate hematological function: Neutrophils=1.5 x109/l and platelet count=100 x109/l; Hb =9g/dl (within 1 week prior to randomization)

9. 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);

10. Written informed consent for participation in the trial.

Exclusion Criteria:

1. Previous exposure to target therapy, chemotherapy, radiotherapy or intervention therapy for colorectal liver metastases.

2. Known or suspected extrahepatic metastases.

3. Patients with known hypersensitivity reactions to any of the components of the study treatments.

4. Having previously participated in a study which included a possibility of being allocated to avastin therapy (whether or not the patient actually received avastin)

5. 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

6. Acute or sub-acute intestinal occlusion

7. Pregnancy (absence confirmed by serum/urine ß-HCG) or breast-feeding

8. 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

9. Known drug abuse/ alcohol abuse

10. Legal incapacity or limited legal capacity

11. Pre-existing peripheral neuropathy.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Neoplasm Metastasis

Intervention

Drug:
• avastin
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.
• mFOLFOX6
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)

Locations

Country	Name	City	State
China	Zhongshan Hospital, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Xu jianmin

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 years
Secondary	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.	3 years
Secondary	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.	3 years
Secondary	tumor response		3 years