DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Doxorubicin and Bortezomib in Treating Patients With Liver Cancer

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

Intervention: doxorubicin (Drug); bortezomib (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Jordan Berlin, Principal Investigator, Affiliation: Vanderbilt-Ingram Cancer Center

Summary

This phase II trial is studying how well giving doxorubicin together with bortezomib works in treating patients with liver cancer. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving doxorubicin together with bortezomib may kill more tumor cells.

Clinical Details

Official title: A Phase II Trial of Bortezomib Plus Doxorubicin in Hepatocellular Carcinoma

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

Primary outcome: Objective Response Rate Measured by Response Evaluation Criteria In Solid Tumors (RECIST)

Secondary outcome:

Overall Survival

Progression Free Survival

Detailed description: PRIMARY OBJECTIVES: I. To evaluate the tumor response rate in patients with hepatocellular carcinoma (HCC). SECONDARY OBJECTIVES: I. To determine other parameters of antitumor effect including time to tumor progression and overall survival in HCC patients treated with bortezomib and doxorubicin. II. To observe toxicity profile of bortezomib and doxorubicin in patients with hepatocellular carcinoma. III. To evaluate proteasome 20S inhibition in tumor tissue (including proteins such as p21, p27, p53, Bax and Bcl-2 which are affected by proteasome 26S) and compare them to clinical parameters using biopsy specimens obtained from patients with HCC treated with bortezomib. (Withdrawn as of 03-2007) IV. To measure phosphorylation of IkB in tumor tissue and compare to clinical parameters using biopsy specimens obtained from patients with HCC treated with bortezomib. (Withdrawn as of 03-2007) V. To evaluate the effect of bortezomib on 26S proteasome activity in peripheral white blood cells (WBC's) and patient serum. Direct measurement of 26S proteasome activity as well as proteins affected by proteasome 26S and Nuclear factor kappa-B (NF-kB) will be analyzed. (Withdrawn as of 03-2007) OUTLINE: This is a multicenter study. Patients receive doxorubicin intravenously (IV) over 5-15 minutes on days 1 and 8. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with no disease progression may continue to receive bortezomib alone in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 13 months.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must have microscopically confirmed hepatocellular carcinoma not amenable to

curative resection; if patients have an isolated lesion in one lobe of the liver, a liver surgeon should determine resectability; central review is not required

- Patients must have measurable disease as determined by Response Evaluation Criteria

In Solid Tumors (RECIST) criteria, amenable to biopsy; patients are not mandated to allow biopsy, even though it is an important aspect of this clinical trial

- Patients with history of malignancy treated within the past 5 years are not eligible;

history of carcinoma-in-situ of cervix, squamous cell cancer of skin, basal cell cancer of skin, previously treated are allowed; others are excluded as recurrence of disease may confuse response rate and/or survival endpoints

- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of

0-2

- Patients must not have had prior systemic chemotherapy for HCC; patients on

antineoplastics for non-malignant diseases, such as methotrexate for rheumatoid arthritis, are allowed, providing patients have been off these agents for at least 4 weeks and all related toxicities have resolved to baseline

- Patients may have had prior embolization without chemotherapy; patients who have had

chemoembolization are not eligible; patients may have had radiofrequency (RF) ablation, cryosurgery or ethanol injection; patients must have documented progression with the involved lesion or at least one previously untreated lesion amenable to biopsy

- Platelet count must be >= 100,000/mm^3 in absence of splenomegaly; platelet count

must be >= 75,000/mm^3 with splenomegaly

- Absolute neutrophil count (ANC) must be >= 1,500/mm^3 in absence of splenomegaly; ANC

must be =< 1,000/mm^3 with splenomegaly

- Alkaline phosphate (ALT) must be =< 5 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) must be =< 5 x institutional ULN

- Bilirubin must be =< 2 mg/dl

- Patients may not exhibit Child Pugh scale grade C cirrhosis

- Serum creatinine=< 2. 0 mg/dl

- All females of childbearing potential must have a blood test or urine study within 2

weeks prior to registration to rule out pregnancy

- Women of childbearing potential and sexually active males are strongly advised to use

an accepted and effective method of contraception

- Patients must not have known bleeding diathesis, international normalized ratio (INR)

> 1. 5 or Partial thromboplastin time (PTT) > 1. 5 x institutional ULN (required due to biopsy portion of study); use of vitamin K or fresh frozen plasma to correct values just prior to biopsy or enrollment is not allowed are not eligible Exclusion criteria:

- Patients have baseline peripheral neuropathy > grade 1

- Patients with history of untreated malignancy other than HCC

- Patients have had prior use of octreotide or tamoxifen as therapy for HCC

- Patients with known allergy to boron, mannitol or bortezomib

- Women are pregnant or breast-feeding (due to the uncertain effects of bortezomib in

the developing fetus and young infants)

- Patients have an underlying medical condition that precludes safe participation in

this clinical trial

- Patients have psychiatric illness or continued substance abuse that may impair the

ability to provide informed consent or prevent safe administration of bortezomib

- Patients with ejection fraction (EF) < 50% measured by Echocardiography (ECHO) or

Multiple gated acquisition (MUGA)

- Patients on verapamil who cannot be switched to an alternative medication (due to the

interaction with doxorubicin)

Locations and Contacts

Eastern Cooperative Oncology Group, Boston, Massachusetts 02215, United States
Additional Information

Starting date: March 2004
Last updated: October 24, 2014

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017