None listed
Conditions
Interventions
Patients will be treated with Bortezomib at a dose of 1.3 mg / m2 IV bolus for 5-15 minutes on days 1, 4, 8, and 11 of each cycle. + Doxorubicin at a dose of 20 mg / m2 IV for 5-15 minutes on days 1 and 8 of each cycle, the days when Doxorubicin is administered with Bortezomib, the former will be administered before the latter. The duration of each cycle is 21 days. As a maximum treatment will be continued for up to 12 cycles, until recurrence or unacceptable toxicity is reported. Doxorubicin ca
Sponsors
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG),
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients must have microscopically confirmed hepatocellular carcinoma not amenable to curative resection. 2. Patients must have measurable disease as determined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, amenable to biops. 3. Patients with history of malignancy treated within the past 5 years are not eligible. 4. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 5. Patients must not have had prior systemic chemotherapy for HCC. 6. Patients may have had prior embolization without chemotherapy. 7. Platelet count must be >= 100,000/mm3 in absence of splenomegaly; platelet count must be >= 75,000/mm3 with splenomegaly. 8. Absolute neutrophil count (ANC) must be >= 1,500/mm3 in absence of splenomegaly; ANC must be = 1.5 or Partial thromboplastin time (PTT) > 1.5 x institutional ULN.
Exclusion criteria
Exclusion criteria: 1. Patients have baseline peripheral neuropathy > grade 1. 2. Patients with history of untreated malignancy other than HCC. 3. Patients have had prior use of octreotide or tamoxifen as therapy for HCC. 4. Patients with known allergy to boron, mannitol or bortezomib. 5. Womenwho are pregnant or breast-feeding. 6. Patients have an underlying medical condition that precludes safe participation in this clinical trial. 7. Patients have psychiatric illness or continued substance abuse that may impair the ability to provide informed consent or prevent safe administration of bortezomib. 8. Patients with ejection fraction (EF) < 50% measured by Echocardiography (ECHO) or Multiple gated acquisition (MUGA). 9. Patients on verapamil who cannot be switched to an alternative medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Clinical evaluation to determine the objective response which is composed of the sum of the complete response and the partial response. Where: 1) Complete response: Disappearance of all target lesions (all measurable lesions, ie, those with> 20 mm greater diameter by conventional means or> 10 mm by CT, up to a maximum of 5 per organ and a total of 10. To be classified as a complete response, the evaluation with CT or other imaging techniques must be repeated in a time not less than 4 weeks after the criteria for response are reached. 2) Partial Response: At least one decrease in 30% of the total sum of the largest diameters of all target lesions. With an imaging confirmation in no less than 4 weeks. Measure:Objective response rate in patients with hepatocellular carcinoma (HCC). Timepoints:4 weeks after reaching an answer. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Clinical evaluation to determine the time to death for any cause (Overall survival) or until the progression of the disease. Where progression is defined as an increase by 20% of the sum of larger diameters of white lesions or occurrence of one or more new lesions and / or unambiguous progression of non-target lesions. The progression of the disease will be evaluated with images such as: CT, MRI. Measure:1) Time to tumor progression. 2) Global survival. Timepoints:When the event occurs. ; Outcome name:Clinical evaluation of adverse events, defined as any adverse medical event resulting from the administration of a study agent, not necessarily caused by it. The type of event will be identified using the NCI Adverse Events Common Terminology Criteria (CTCAE), version 3.0. They will be graded according to their severity, their relationship with the study drug will be determined and also previous experiences of the adverse effect. Complete physical examination. Laboratory tests: Hematological and hepatic panels, creatinine, TP, INR, aPTT. Measure:Safety and toxicity: Incidence of adverse events, alterations in physical examination and vital signs and laboratory tests. Timepoints:Clinical evaluation of adverse events: Weekly during the first cycle, at the beginning of each subsequent cycle and at the end of the treatment (Maximum 4 weeks). Complete physical examination, laboratory tests: At the beginning of each cycle and at the end of the treatment (Maximum 4 weeks). ; Outcome name:1) Inhibition of the 20S proteasome: tissue biopsies will be performed where the activity of the 20S proteosome will be directly evaluated, including proteins such as p21, p27, p53, Bax and Bcl-2. 2) Phosphorylation of IkB: Tissue biopsies will be performed to determine the phosphorylation of IkB which is inactivated due to the activity of the 20S proteosome. 3) 26S proteosome activity: Samples of white blood cells will be made fr | — |
Countries
Peru, United States
Outcome results
None listed