Cetuximab in Patients With Unresectable or Metastatic Hepatocellular Carcinoma

This study has been completed.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Bristol-Myers Squibb
Information provided by (Responsible Party):
Andrew X. Zhu, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00142428
First received: August 31, 2005
Last updated: March 16, 2014
Last verified: March 2014
  Purpose

The main purpose of this study is to begin to collect information and to try to learn whether or not cetuximab works in treating patients with unresectable or metastatic hepatocellular carcinoma.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Cetuximab in Patients With Unresectable or Metastatic Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Progression free survival in patients treated with cetuximab for unresectable or metastatic hepatocellular carcinoma [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Objective Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: January 2005
Study Completion Date: October 2008
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab
The initial dose of cetuximab was 400 mg/m2 (cycle 1 only) given intravenously followed by weekly intravenous infusions at 250 mg/m2. Each cycle was defined as 6 consecutive weekly intravenous treatments. Treatment was continued until 1 of the following criteria was met: disease progression per RECIST criteria, unacceptable toxicity, patient refusal, or the need to delay therapy more than 3 weeks.
Drug: Cetuximab
The initial dose of cetuximab was 400 mg/m2 (cycle 1 only) given intravenously followed by weekly intravenous infusions at 250 mg/m2. Each cycle was defined as 6 consecutive weekly intravenous treatments. Treatment was continued until 1 of the following criteria was met: disease progression per RECIST criteria, unacceptable toxicity, patient refusal, or the need to delay therapy more than 3 weeks.

Detailed Description:

The first step in this study is to examine the tumor biopsy (previously collected) and determine whether or not it is epidermal growth factor receptor (EGFR) positive or EGFR negative. Both EGFR positive and EGFR negative patients can participate in this study because at this time it is not known whether having a negative or positive receptor makes a difference in how the study drug works on the tumor. By knowing if the tumor is EGFR positive or negative, we will be able to see if there is a difference in the way the tumor responds to cetuximab.

Patients will receive cetuximab intravenously once weekly for 6 weeks. Each 6-week period is one cycle of treatment. The first dose of cetuximab is larger than the following doses.

For the first clinic visit the patient's blood pressure, temperature, breathing and heart rate will be taken before, during, at the end, and one-hour after the cetuximab has been administered. For each visit after that, blood pressure, temperature, breathing and heart rate will be taken before and after cetuximab has been administered.

Before each administration of cetuximab, diphenhydramine will also be administered to decrease the chances of an allergic or hypersensitivity reaction.

The following tests and procedures will be performed at weeks 1, 3 and 5 during each 6-week cycle of treatments as well as at the end of study treatment: physical exam, vital signs, medical history and blood work. At the end of each 6-week cycle a CT and/or MRI will be performed to measure the tumor size.

Long-term follow-up will include physical exams and bloodwork every 6 months.

Patients will remain on cetuximab as long as there is no disease progression or intolerable side effects.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Unresectable or metastatic hepatocellular carcinoma
  • Measurable tumor
  • Adequate hepatic function: total bilirubin < 3.0mg/dl; AST < 7 x upper limit of normal (ULN).
  • Adequate renal function: serum creatinine < 2.0mg/dl
  • Adequate bone marrow function: absolute neutrophil count (ANC) > 1,000/mm3; platelets > 75,000/mm3.
  • 0-2 prior systemic chemotherapy regimens for hepatocellular carcinoma
  • 18 years of age and older
  • ECOG performance status of 0-2
  • Life expectancy > 12 weeks

Exclusion Criteria:

  • Surgery, excluding prior diagnostic biopsy or venous access device placement, within 28 days of study entry
  • Uncontrolled serious medical or psychiatric illness
  • Irradiation or chemotherapy for disease within 28 days of study entry
  • Clinically apparent central nervous system metastases or carcinomatous meningitis
  • Received an investigational agent within 30 days
  • Cancer of the Liver Italian Program (CLIP) score > 3
  • Acute hepatitis
  • Active or uncontrolled infection
  • Significant history of cardiac disease
  • Prior cetuximab or other therapy which specifically and directly targets the EGFR pathway
  • Prior allergic reaction to chimerized or murine monoclonal antibody therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00142428

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Bristol-Myers Squibb
Investigators
Principal Investigator: Andrew X. Zhu, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Andrew X. Zhu, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00142428     History of Changes
Other Study ID Numbers: 04-347
Study First Received: August 31, 2005
Last Updated: March 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Hepatocellular carcinoma
cetuximab
Unresectable hepatocellular carcinoma
Metastatic hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014