Phase II Trial of PS-341 in Patients With Hepatocellular Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- bortezomib
- Conditions
- Adult Primary Hepatocellular Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 55
- Locations
- 1
- Primary Endpoint
- Proportion of confirmed tumor responses, defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 6 weeks apart
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This phase II trial is studying how well bortezomib works in treating patients with hepatocellular carcinoma (liver cancer) that cannot be removed with surgery. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
Detailed Description
PRIMARY OBJECTIVES: I. Proportion of confirmed tumor responses. SECONDARY OBJECTIVES: I. To evaluate the confirmed and objective response rate. II. To assess patient outcome as estimated by duration of response, time to disease progression, and survival. III. To evaluate the adverse event rates associated with PS-341 in this population. IV. To explore the relationships between laboratory correlates (eg. IHC) and patient outcome (eg p53 and disease progression). V. To evaluate alterations in laboratory correlates from pre-treatment measurements (ie, pre and post treatment). The following immunohistochemistry (IHC) assays will be performed: IHC of p53, IHC of p21, IHC of p27, IHC of NFkB, IHC of Ki67. OUTLINE: This is a multicenter study. Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 3 years from study entry.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed hepatocellular carcinoma (HCC) that is not amenable to surgical resection
- •Must have measurable disease; NOTE: For patients having only lesions measuring \> 1 cm to =\< 2 cm must use spiral CT imaging for all tumor assessments
- •Absolute neutrophil count (ANC) \>= 1500/mm\^3
- •PLT \>= 75,000/mm\^3
- •Total bilirubin =\< 3 x upper normal limit (UNL)
- •Serum AST =\< 5 x UNL
- •Serum ALT =\< 5 x UNL
- •Serum creatinine =\< 2 mg/dL
- •Serum albumin \>= 2.5 g/dL
- •PT/ INR =\< 1.5 (EXCEPTION - Patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose, \>= 2 weeks, of warfarin or low molecular weight heparin and has an PT/INR range 2-3)
Exclusion Criteria
- •Any of the following:
- •Prior systemic anticancer therapy. Note: Chemoembolization is allowed and for trial purposes is not considered a systemic chemotherapy; however, \>= 6 weeks must have elapsed between chemoembolization and enrollment on this study
- •Prior PS-341 therapy
- •Immunotherapy =\< 4 weeks have elapsed prior to study entry
- •Biologic therapy =\< 4 weeks have elapsed prior to study entry
- •Radiation therapy =\< 4 weeks have elapsed prior to study entry
- •Cryotherapy =\< 6 weeks have elapsed since prior to study entry
- •Radiofrequency ablation =\< 6 weeks have elapsed since prior to study entry
- •Ethanol injection =\< 6 weeks have elapsed since prior to study entry
- •Photodynamic therapy =\< 6 weeks have elapsed since prior to study entry
Arms & Interventions
Treatment (bortezomib)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: bortezomib
Treatment (bortezomib)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Proportion of confirmed tumor responses, defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 6 weeks apart
Time Frame: Up to 36 weeks (12 courses)
Ninety-five percent confidence intervals for the true success proportion will be calculated.
Secondary Outcomes
- Survival time(Time from registration to death due to any cause, assessed up to 3 years)
- Time to disease progression(Time from registration to documentation of disease progression, assessed up to 3 years)
- Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented(Up to 3 years)
- Time to treatment failure(Time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 3 years)