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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Fudan University
Sponsor:
Information provided by (Responsible Party):
Xu jianmin, Fudan University
ClinicalTrials.gov Identifier:
NCT01564810
First received: March 26, 2012
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

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


Condition Intervention Phase
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Drug: Cetuximab
Drug: chemotherapy of mFOLFOX6 or FOLFIRI
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of Cetuximab in Combination With Chemotherapy for the First Treatment of Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Fudan University:

Primary Outcome Measures:
  • the rate of patients converted to resection for liver metastases [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    defined as partial and complete response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors).


Estimated Enrollment: 150
Study Start Date: September 2006
Estimated Study Completion Date: September 2015
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: mFOLFOX6

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01564810

Contacts
Contact: jianmin xu jianmin xu, doctor 008613501984869 xujmin@yahoo.com.cn

Locations
China, Shanghai
Zhongshan Hospital, Fudan University Recruiting
Shanghai, Shanghai, China, 200000
Contact: jianmin xu , doctor    008613501984869    xujmin@yahoo.com.cn   
Sponsors and Collaborators
Xu jianmin
  More Information

No publications provided by Fudan University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Xu jianmin, Jianmin Xu, PhD Fudan University, Fudan University
ClinicalTrials.gov Identifier: NCT01564810     History of Changes
Other Study ID Numbers: 2012-03
Study First Received: March 26, 2012
Last Updated: October 23, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Fudan University:
liver metastasis
colorectal cancer
cetuximab
chemotherapy

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014