Study of Sorafenib and Gemcitabine in Advanced Hepatocellular Carcinoma (HCC)

NCT00844688 | Unknown Phase 2 DMC

• 1 other identifier: HCC
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

For the majority of patients, metastatic HCC is incurable and patients should be considered candidates for clinical trials when appropriate. Till recently there was no worldwide, approved local or systemic therapy for advanced HCC and the available therapies for advanced unresectable and/or metastatic HCC have limited clinical values, with low response rates and little impact on the natural history of the disease. Furthermore, the toxicities associated with these agents can be severe, requiring careful patient selection, and this dramatically decreases the number of patients who may benefit from therapy. The SHARP trial established the survival benefit of Sorafenib in Advanced HCC but the results yet remain humble. The need for more effective therapies is still there. Study Objectives The primary objective of this phase II study is to evaluate the efficacy and safety of Sorafenib and Gemcitabine combination in patients with advanced HCC. Safety data and limited efficacy data will be collected for this combination in the study. All Drug-Related Adverse Events, all Adverse Events NCI CTCAE Version 3.0 Grade 3 or higher, and all Serious Adverse Events regardless of causal relationship to study drugs will be recorded in this study.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Sorafenib; Gemcitabine

Outcome Measures

Primary Outcomes (1)

• RECIST criteria for response evaluation by CT sacan abdomen in Target lesion of HCC

  4 months

Secondary Outcomes (1)

• Toxicity evaluation in accordance with CTCAE v3.0

  4 months

Study Arms (1)

sorafenib/gemcitabine

OTHER

Drug: sorafenib; Drug: Gemcitabine

Interventions

sorafenib DRUG

Patients will be treated with 400 mg oral sorafenib twice a day on a continuous basis. Patients in this protocol may continue to be treated with this combination for a minimum of 4 cycles until any of the following criteria for protocol discontinuation is reached: 1. Progression of disease. 2. The patient is unlikely to benefit from further treatment as Judged by the Investigator. 3. Intolerable toxicity of the drugs. 4. Withdrawal of consent for any reason.

Also known as: Nexavar

sorafenib/gemcitabine

Gemcitabine DRUG

Patients will be treated with Gemcitabine 1000mg/m2 administered on day 1 \& 8 of a 4 week cycle. Patients in this protocol may continue to be treated with this combination for a minimum of 4 cycles until any of the following criteria for protocol discontinuation is reached: Progression of disease. The patient is unlikely to benefit from further treatment as Judged by the Investigator. Intolerable toxicity of the drugs. Withdrawal of consent for any reason.

Also known as: Gemzar

sorafenib/gemcitabine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced Hepatocellular carcinoma
• Histologically proven
• Child-Pugh A and B
• Age \> 18 years.
• ECOG Performance Status of 0 or1
• Life expectancy of at least 12 weeks.
• Subjects with at least one uni-dimensional (for RECIST) or bi-dimensional (for WHO) measurable lesion. Lesions must be measured by CT-scan or MRI
• Adequate bone marrow, liver and renal function as assessed by the following
• Hemoglobin \> 9.0 g/dl
• Absolute neutrophil count (ANC) \>1,500/mm3
• Platelet count ³ 100,000/μl
• Total bilirubin \< 1.5 times the upper limit of normal
• ALT and AST \< 2.5 x upper limit of normal (\< 5 x upper limit of normal for patients with liver involvement of their cancer)
• Alkaline phosphatase \< 4 x ULN
• PT-INR/PTT \< 1.5 x upper limit of normal \[Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.\]

You may not qualify if:

• History of cardiac disease: congestive heart failure \>NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or Digoxin are permitted) or uncontrolled hypertension.
• History of HIV infection
• Active clinically serious infections (\> grade 2 NCI-CTC version 3.0)
• Symptomatic metastatic brain or meningeal tumors (unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft however, the organ allograft may be allowed as protocol specific.
• Patients with evidence or history of bleeding diasthesis
• Patients undergoing renal dialysis
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry.
• Excluded therapies and medications, previous and concomitant:
• Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.
• Major surgery within 4 weeks of start of study
• Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. \[G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.\] \[Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study\]
• Investigational drug therapy outside of this trial during or within 4 weeks of study entry
• Prior exposure to the study drug.

Sponsors & Collaborators

• Combined Military Hospital, Pakistan: lead
• Bayer: collaborator

Study Sites (1)

Combined Military Hospital

Rawalpindi, Punjab Province, 46000, Pakistan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib; Gemcitabine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines

Study Officials

• Naeem Naqi, MBBS,FCPS

  Consultant Oncologist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Naeem Naqi, MBBS,FCPS

CONTACT

00923008435646; naqi60@hotmail.com

Ahsan Mahmood, MBBS,FCPS

CONTACT

00923215120482; ahsan_mahmood@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 13, 2009
• First Posted: February 16, 2009
• Study Start: September 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: December 1, 2009
• Last Updated: February 16, 2009

Record last verified: 2009-02

Locations

PA (1)