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Phase II Trial of PS-341 in Patients With Hepatocellular Carcinoma

Phase 2
18 Years
Not Enrolling
Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer

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Trial Information

Phase II Trial of PS-341 in Patients With Hepatocellular Carcinoma


I. Proportion of confirmed tumor responses.


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.

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)

- Child-Pugh classification of A or B

- Patients may not have received prior systemic chemotherapy BUT may have received
prior chemoembolization, cryotherapy, radiofrequency ablation, ethanol injection, or
photodynamic therapy, provided the following criteria are met:

- > 6 weeks has elapsed since that therapy

- Indicator lesion(s) is/are outside the area of prior treatment or, if the only
indicator lesion is inside the prior treatment area, there must be clear
evidence of disease progression associated with that lesion

- Edges of the indicator lesion are clearly distinct on CT scanning

- ECOG performance status (PS) 0, 1, or 2

- Estimated life expectancy >= 24 weeks

- Capable of understanding the investigational nature, potential risks and benefits of
the study and able to provide written informed consent

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

- Major surgery, or significant traumatic injury =< 3 weeks prior to study entry

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any other therapy
or supportive care considered investigational

- Presence of > grade 1 sensory peripheral neuropathy of any etiology OR grade 1 with
neuropathic pain of any etiology

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to PS-341

- History of other malignancy =< 3 years prior to study entry, except for adequately
treated basal cell or squamous cell skin cancer

- Any of the following as this regimen may be harmful to a developing fetus or nursing

- Pregnant women

- Breastfeeding women

- Men or women of childbearing potential or their sexual partners who are
unwilling to employ adequate contraception (condoms, diaphragm, birth control
pills, injections, intrauterine device [IUD], surgical sterilization,
subcutaneous implants, or abstinence, etc.)

- Known CNS metastases

- Uncontrolled intercurrent illness including, but not limited to:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris, cardiac arrhythmia

- Psychiatric illness that would limit compliance with study requirements

- HIV-positive patients receiving combination anti-retroviral therapy

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

Ninety-five percent confidence intervals for the true success proportion will be calculated.

Outcome Time Frame:

Up to 36 weeks (12 courses)

Safety Issue:


Principal Investigator

George Kim

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

April 2005

Completion Date:

Related Keywords:

  • Adult Primary Hepatocellular Carcinoma
  • Advanced Adult Primary Liver Cancer
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
  • Carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



Mayo Clinic Rochester, Minnesota  55905