Sorafenib With Capecitabine for Patients With Measurable Hepatocellular Carcinoma

This study has been terminated.
(Low accrual rate)
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier:
NCT01032850
First received: December 14, 2009
Last updated: June 13, 2016
Last verified: June 2016
  Purpose

This research study will evaluate Sorafenib (Nexavar®) and Capecitabine (Xeloda®) to see the following:

  • how effective this combination of study drugs will be in treating HCC
  • how long subjects respond to these study drugs
  • what types of side effects can be expected, and
  • how severe the side effects are

All subjects in this study will receive:

  • Sorafenib twice a day by mouth
  • Capecitabine twice a day by mouth

Treatment will be given in a 28-day treatment cycle.

Subjects will take sorafenib every day of the cycle. Subjects will take capecitabine on days 1-7 and 15-21 of the cycle


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Sorafenib & Capecitabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sorafenib in Combination With Capecitabine for Patients With Measurable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by New Mexico Cancer Care Alliance:

Primary Outcome Measures:
  • Number of Participants Experiencing Adverse Events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The primary objective of the study is to evaluate safety and tolerability of the study treatment regimen. The analyses will be descriptive and no formal hypotheses testing will be performed. Toxicities (i.e. Adverse Events) are evaluated prior to each treatment and during any clinical visit.


Secondary Outcome Measures:
  • Disease Control Rate of Response (DCR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI:) Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Disease control rate (DCR) is the sum of the percentages of patients achieving complete and partial responses and stable disease

  • Overall Survival (OS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The time from treatment initiation to death by any cause

  • Progression Free Survival (PFS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI:) Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.


Enrollment: 15
Study Start Date: September 2009
Study Completion Date: September 2015
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Sorafenib & Capecitabine
Intervention: Sorafenib & Capecitabine: Sorafenib twice a day by mouth (400mg) Capecitabine twice a day by mouth (850mg)
Drug: Sorafenib & Capecitabine
Intervention: Sorafenib twice a day by mouth (400mg), Capecitabine twice a day by mouth (850mg). One cycle of treatment will consist of capecitabine on days 1-7 and 15-22 while sorafenib will be given daily continuously. Cycles will be repeated every 28 days.
Other Names:
  • Sorafenib
  • Capecitabine
  • Nexavar
  • Xeloda

Detailed Description:

Hepatocellular carcinoma (HCC), also known as primary liver cancer, is the most common form of liver cancer and is responsible for 80 percent of the primary malignant liver tumors in adults. It is the fifth most common cancer in the world. HCC disproportionately affects men, with four times as many men developing the disease as women. In 2002, approximately 626,000 cases of HCC were reported worldwide (15,000 in the United States and 53,600 in Europe), and more than 600,000 deaths (about 13,000 Americans and 57,000 Europeans) due to HCC were reported. The five-year relative survival rate is about seven percent.

The Gem-Ox regimen has been used in the treatment of pancreatic cancer with encouraging results. Preliminary results of the Gem-Ox combination have been encouraging as well.Based on these observations the possibility of adding bevacizumab, a monoclonal antibody against VEGF, is being studied by other investigators. However, the combination of GEM-OX with bevacizumab is unlikely to be tolerated by HCC patients with Child-Pugh class B and C liver cirrhosis especially those with significant thrombocytopenia.It would seem therefore that the agents that could be tolerated by cirrhotic patients with advanced HCC would include capecitabine, erlotinib and sorafenib. We propose this phase II trial of sorafenib + capecitabine combination in patients with HCC and advanced liver cirrhosis who have a platelet count of ≥ 40,000 and a Child-Pugh (C-P) class A-and B liver cirrhosis with a life expectancy of ≥16 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Histologic diagnosis of hepatocellular carcinoma The lesion or lesions are not resectable with curative intent. Prior loco-regional treatment (resection, RFA, chemoembolization) is allowed.

Adequate bone marrow function:

  • Absolute neutrophil count (AGC) >1500/µL
  • Platelet count >60,000 /µL

Renal function:

  • Serum creatinine < 2.0 mg/dl, and a calculated CCT of > 30 mL/min. Hepatic function:(Patients with a Child-Pugh (C-P) class A-B)
  • Bilirubin < 2.8 mg/dl (provided the Child-Pugh class of liver cirrhosis is A or B (7) (ie. The Child-Pugh score is only 7 points)
  • ALT and AST ≤ 5.0 times the ULN • Hemoglobin > 8.5 g/dl

ECOG/Zubrod/SWOG Performance Status = 0>1 Life expectancy > 16 weeks Male or female' age >18 years Patients of childbearing potential must be using an effective means of contraception.

INR < 1.5 or a PT/PTT within normal limits.

Exclusion Criteria:

  • Any prior systemic therapy including chemotherapy of targeted agents
  • Uncontrolled ascites defined as not easily controlled by stable doses of diuretics.
  • Pregnant or lactating females
  • Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • Uncontrolled' clinically significant dysrhythmia
  • History of prior malignancy within the prior 3 years, with the exception of non-melanoma carcinomas of the skin, carcinoma in situ of the cervix or breast, Rai Stage I chronic lymphocytic leukemia and superficial bladder cancer.
  • Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor growth in that lesion
  • Uncontrolled metastatic disease of the central nervous system
  • Radiotherapy within the 2 weeks before Cycle 1' Day 1
  • Surgery within the 2 weeks before Cycle 1' Day 1
  • Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications.
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Known human immunodeficiency virus (HIV) infection.
  • Patients with chronic Hepatitis B or C infections are eligible.
  • Active clinically serious infection > CTCAE Grade 2.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Serious non-healing wound, ulcer, or bone fracture.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Use of St. John's Wort or rifampin (rifampicin).
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any malabsorption problem.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01032850

Locations
United States, New Mexico
University of New Mexico Cancer Center @ Lovelace Medical Center
Albuquerque, New Mexico, United States, 87102
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
Cancer Center at Presbyterian Hospital
Albuquerque, New Mexico, United States, 87110
Sponsors and Collaborators
New Mexico Cancer Care Alliance
Bayer
Investigators
Principal Investigator: Yehuda Z. Patt, MD University of New Mexico Cancer Center
  More Information

Additional Information:
Responsible Party: New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier: NCT01032850     History of Changes
Other Study ID Numbers: INST 0820  NCI-2011-02945 
Study First Received: December 14, 2009
Results First Received: June 6, 2015
Last Updated: June 13, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by New Mexico Cancer Care Alliance:
INST 0820
sorafenib
capecitabine
hepatocellular carcinoma
lung
nexavar
xeloda
liver cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Capecitabine
Sorafenib
Niacinamide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 30, 2016