Clinical trial NCT00006016: Thalidomide and Chemoembolization With Doxorubicin in Treating Patients With Liver Cancer That Cannot be Removed by Surgery
Official title: An Evaluation of Chronic Thalidomide Administration in Patients Undergoing Chemoembolization for Unresectable Hepatocellular Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying the effectiveness of combining thalidomide and chemoembolization in treating patients who have liver cancer that cannot be removed by surgery. Thalidomide may stop the growth of liver cancer by stopping blood flow to the tumor. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Combining thalidomide with chemoembolization may kill more tumor cells.

Detailed description: OBJECTIVES:

I. Determine the feasibility and potential activity of thalidomide in patients with unresectable hepatocellular carcinoma who are undergoing chemoembolization to predominant tumor masses.

II. Determine the toxicity of this regimen of these patients. III. Determine the overall survival of patients treated with this regimen. IV. Determine the serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor alpha in patients treated with this regimen.

OUTLINE:

Patients receive oral thalidomide daily beginning 4 weeks before the first planned chemoembolization procedure. Thalidomide administration is stopped 24 hours before each chemoembolization procedure, and then restarted at 24 hours after completion of each procedure OR when blood counts and levels of bilirubin and transaminases recover, whichever occurs later. Thalidomide treatment continues in the absence of disease progression or unacceptable toxicity.

Patients undergo placement of a visceral arterial catheter. Patients receive doxorubicin as a chemoemulsion via the arterial catheter into 1 hepatic lobe only under angiographic guidance. Immediately after delivery of the chemoemulsion, patients undergo particulate embolization. The opposite lobe, if involved, is treated within 3-5 weeks of treatment of the initial lobe. Patients are reevaluated for repeat chemoembolization within 8-12 weeks of the last chemoembolization. For eligible patients, each lobe is treated separately a second time, in the same sequence, in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study within 18 months.

Eligibility criteria: Inclusion Criteria:

* Histologically proven hepatocellular carcinoma
* Ineligible for potentially curative surgical resection
* Must be a candidate for palliative chemoembolization

  * MRI must show one or more discrete tumor nodules that can be targeted by angiography for chemoembolization

    * No diffusely infiltrating tumor
  * Lesions under consideration for chemoembolization must demonstrate substantial hypervascularity
* Performance status - ECOG 0-2
* Absolute neutrophil count at least 1,200/mm\^3
* Hemoglobin at least 8.0 g/dL
* Platelet count at least 50,000/mm\^3
* SGOT and SGPT no greater than 5 times normal
* Bilirubin less than 3 mg/dL
* Creatinine no greater than 1.5 mg/dL
* No other medical condition that would preclude study participation
* No other malignancy within the past 5 years except curatively resected basal cell skin cancer or carcinoma in situ of the cervix
* Not pregnant or nursing
* Negative pregnancy test
* Regardless of fertility status:

  * All female patients (unless they have undergone a hysterectomy or have been amenorrheic or postmenopausal for at least 2 years) must use at least 1 highly active method of contraception AND 1 additional effective method of contraception at least 4 weeks before, during, and for at least 4 weeks after study participation
  * All male patients (even if they have undergone a successful vasectomy) must use effective barrier contraception during and for at least 4 weeks after study participation
* Prior interferon for hepatitis allowed
* No prior biologic therapy for hepatocellular carcinoma (HCC)
* No prior chemotherapy for hepatocellular carcinoma (HCC)
* No concurrent barbiturates or alcohol

Primary outcomes:
measure: Survival
timeFrame: Up to 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
Study officials:
affiliation: NYU Langone Health
name: Alec Goldenberg
role: PRINCIPAL_INVESTIGATOR
References: