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Cetuximab in Combination With Chemotherapy for the Treatment of Metastatic Colorectal Cancer

Primary Purpose

Colorectal Neoplasms, Neoplasm Metastasis, Liver Neoplasms

Status

Unknown status

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Cetuximab

chemotherapy of mFOLFOX6 or FOLFIRI

About this trial

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

Eligibility Criteria

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

Inclusion Criteria:

Age ≥ 18 and ≤ 75 years;
Primary tumour has undergone radical resection and histologically confirmed colorectal adenocarcinoma;
Together with clinical or radiological evidence of first occurrence of non-resectable synchronous liver-only metastases
With evidence of tumor EGFR expression and KRAS gene wild-type status;
With 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 cetuximab therapy (whether or not the patient actually received cetuximab)
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 UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

patients received cetuximab in combination with chemotherapy

Patients received chemotherapy (mFOLFOX6 or FOLFIRI) alone. mFOLFOX6 (day 1, oxaliplatin 85 mg/m², folinic acid 400 mg/m², and fluorouracil 400 mg/m² intravenous bolus, then 2400 mg/m² over 46 h continuous infusion) FOLFIRI (day 1, irinotecan 180mg/m2, folinic acid 400 mg/m², and fluorouracil 400 mg/m² intravenous bolus, then continuous infusion for 46 hours of 2400 mg/m2).

Outcomes

Primary Outcome Measures

the rate of patients converted to resection for liver metastases

To explore whether cetuximab in combination with chemotherapy as treatment could improve the resection rate in patients with KRAS wild-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 cetuximab 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.

overall survival

OS and MST 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

defined as partial and complete response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors).

Full Information

NCT ID

NCT01564810

First Posted

March 26, 2012

Last Updated

October 23, 2012

Sponsor

Xu jianmin

1. Study Identification

Unique Protocol Identification Number

NCT01564810

Brief Title

Cetuximab in Combination With Chemotherapy for the Treatment of Metastatic Colorectal Cancer

Official Title

Study of Cetuximab in Combination With Chemotherapy for the First Treatment of Metastatic Colorectal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2012

Overall Recruitment Status

Unknown status

Study Start Date

September 2006 (undefined)

Primary Completion Date

June 2012 (Actual)

Study Completion Date

September 2015 (Anticipated)

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 Cetuximab in combination with chemotherapy in the treatment of unresectable metastatic colorectal cancer.

Detailed Description

Patients will be eligible for inclusion if their primary tumors have been resected and if the patients have histologically confirmed wild-type-KRAS colorectal adenocarcinoma with synchronous liver-confined metastases deemed non-resectable. Eligible patients will be randomly assigned to chemotherapy plus cetuximab (arm A) or chemotherapy alone (arm B). Treatment will be planned to commence between 2 and 4 weeks after the primary surgery. 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 2 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, Neoplasm Metastasis, Liver Neoplasms

Keywords

liver metastasis, colorectal cancer, cetuximab, chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

patients received cetuximab in combination with chemotherapy

Arm Title

Arm B

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cetuximab

Other Intervention Name(s)

Erbitux

Intervention Description

On day 1 of a 14 day treatment cycle, patients received a 2-hour infusion of cetuximab (initial dose 400 mg/m2 in week 1, and 250 mg/m2 weekly during 1 hour thereafter) followed after 1 hour by chemotherapy of FOLFOX or FOLFIRI until progressive disease or unacceptable toxicity.

Intervention Type

Drug

Intervention Name(s)

chemotherapy of mFOLFOX6 or FOLFIRI

Other Intervention Name(s)

mFOLFOX6

Intervention Description

FOLFOX-4 (oxaliplatin, 85mg/m2 on day 1 infused during 2 hours;LV200mg/m2ondays 1and 2 infused during 2 hours, together with or following oxaliplatin; followed by FU 400 mg/m2 intravenous bolus then 600 mg/m2 intravenous infusion over 22 hours on days 1 and 2) FOLFIRI(irinotecan 180mg/m2 on day 1 infused during 2 hours; fluorouracil in a bolus of 400 mg/m2 and then continuous infusion for 46 hours of 2400 mg/m2)

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 and MST 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

Description

defined as partial and complete response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors).

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 has undergone radical resection and histologically confirmed colorectal adenocarcinoma; Together with clinical or radiological evidence of first occurrence of non-resectable synchronous liver-only metastases With evidence of tumor EGFR expression and KRAS gene wild-type status; With 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 cetuximab therapy (whether or not the patient actually received cetuximab) 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

jianmin xu jianmin xu, doctor

Phone

008613501984869

xujmin@yahoo.com.cn

Facility Information:

Facility Name

Zhongshan Hospital, Fudan University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

jianmin xu, doctor

Phone

008613501984869

xujmin@yahoo.com.cn

12. IPD Sharing Statement

Citations:

PubMed Identifier

23569301

Citation

Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. doi: 10.1200/JCO.2012.44.8308. Epub 2013 Apr 8.

Results Reference

derived

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Cetuximab in Combination With Chemotherapy for the Treatment of Metastatic Colorectal Cancer

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