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

October 23, 2012 updated by: Xu jianmin

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

In this study, the investigators assessed the effect of Cetuximab in combination with chemotherapy in the treatment of unresectable metastatic colorectal cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Recruiting
        • Zhongshan Hospital, Fudan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm A
patients received cetuximab in combination with chemotherapy
Drug: Cetuximab
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.
Other Names:
  • Erbitux
Drug: chemotherapy of mFOLFOX6 or FOLFIRI
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)
Other Names:
  • mFOLFOX6
ACTIVE_COMPARATOR: Arm B
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).
Drug: chemotherapy of mFOLFOX6 or FOLFIRI
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)
Other Names:
  • mFOLFOX6

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the rate of patients converted to resection for liver metastases
Time Frame: 3 years
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.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression free survival
Time Frame: 3 years
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.
3 years
overall survival
Time Frame: 3 years
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.
3 years
tumor response
Time Frame: 3 years
defined as partial and complete response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors).
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xu jianmin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (ACTUAL)

June 1, 2012

Study Completion (ANTICIPATED)

September 1, 2015

Study Registration Dates

First Submitted

March 26, 2012

First Submitted That Met QC Criteria

March 27, 2012

First Posted (ESTIMATE)

March 28, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

October 24, 2012

Last Update Submitted That Met QC Criteria

October 23, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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