Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01666756
First received: August 14, 2012
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

This phase I trial studies the side effects and best dose of Chinese herbal formulation PHY906 when given together with sorafenib tosylate in treating patients with advanced liver cancer. Biological therapies, such as Chinese herbal formulation PHY906, may interfere with the growth of tumor cells and slow the growth of tumors. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of liver cancer by blocking blood flow to the tumor. Giving Chinese herbal formulation PHY906 together with sorafenib tosylate may work better in treating advanced liver cancer.


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Dietary Supplement: Chinese herbal formulation PHY906
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Open Label Study Investigating the Combination of KD018 and Sorafenib (Nexavar) in Patients With Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Recommended phase II dose, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adverse events as determined by NCI CTCAE version 4 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Serious adverse events as determined by NCI CTCAE version 4 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Discontinuation rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Dose adjustment rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Tumor response in terms of best overall response, assessed using RECIST [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Sorafenib tosylate concentration after co-administration with Chinese herbal formulation PHY906 [ Time Frame: Baseline; 1 hour post-dose; 2 hours post-dose ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change in cytokine/chemokine levels [ Time Frame: Baseline to up to 6 years ] [ Designated as safety issue: No ]
  • Change in levels of soluble biomarkers [ Time Frame: Baseline to up to 6 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: May 2013
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Chinese herbal formulation PHY906 and sorafenib)
Patients receive Chinese herbal formulation PHY906 PO BID on days 1-4, 8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dietary Supplement: Chinese herbal formulation PHY906
Given PO
Other Name: PHY-906
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to take oral drugs
  • Diagnosis of advanced hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases (AASLD) guidelines
  • HCC stage B or C according to the Barcelona Clinic Liver Cancer (BCLC)
  • Previous or current use of sorafenib allowed
  • Measurable disease according to RECIST, i.e. at least one measurable lesion; this lesion should not have been previously treated with local therapy; a treated lesion may be used where these lesions are the only lesions available for evaluation and have shown definite progression since their last local treatment; local therapy must have been completed at least four weeks prior to baseline evaluation
  • Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Cirrhotic status of current Child-Pugh class A and B with no encephalopathy and no ascites (ascites controlled by diuretics is also excluded in this study); Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period
  • For patients with positive HBV-deoxyribonucleic acid (DNA) and/or positive of hepatitis B surface antigen (HBsAg) results, they must be treated with anti-virals, as prophylaxis at least 1-2 weeks prior to receiving study drug, cycle 1, day 1
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelets >= 75000 x 10^6/L
  • Hemoglobin (Hgb) >= 9 g/dL
  • Alanine aminotransferase (ALT) =< 5 x upper limit of normal (ULN)
  • Serum creatinine =< 1.5 x ULN
  • Ability to understand and willingness to sign a written informed consent and to be able to follow the visit schedule
  • Life expectancy of approximately 6 months
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; should a woman become pregnant, or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • All subjects must have the ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

  • Previous or current use of sorafenib and previous use of tamoxifen is allowed as previous systemic therapy
  • Patients currently receiving any anti-cancer therapy, except sorafenib, or who have received any local anti-cancer therapy =< 4 weeks prior to baseline computed tomography (CT)/magnetic resonance imaging (MRI) scan, prior to cycle 1 treatment
  • Active bleeding during the last 30 days prior to cycle 1 treatment including variceal bleeding (esophageal varices should be treated according to standard practice e.g. ligation/banding and procedure completed 30 days prior to cycle 1 treatment
  • Patients with a known hypersensitivity to KD018 or known hypersensitivity to sorafenib or contraindications to sorafenib based on the local sorafenib label
  • Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
  • Any severe and/or uncontrolled medical conditions including:

    • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to course 1 treatment, serious uncontrolled cardiac arrhythmia, uncontrolled hypertension
    • Previous transient ischemic attack (TIA), cerebral vascular accident (CVA), symptomatic posterior vitreous detachment (PVD) within last 6 months of cycle 1 treatment
    • Congenital long QT syndrome
    • Patients with active alcohol intake
    • Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy, in the opinion of the investigator, except chronic HBV or HCV
    • Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
  • Patients receiving chronic treatment with corticosteroids (except for intermittent topical or local injection or aldosterone) or another immunosuppressive agent
  • Patients treated with drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A (CYP3A) unless the drugs are medically necessary and no substitutes are available
  • Patients who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from surgery
  • Patients who have received an investigative drug or therapy within the last 30 days prior to cycle 1 treatment
  • Pregnant and/or breastfeeding women
  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: NCT01666756

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Yun Yen    800-826-4673    yyen@coh.org   
Principal Investigator: Yun Yen         
United States, Pennsylvania
University of Pittsburgh Medical Center Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Edward Chu, MD    412-648-6589    chue2@upmc.edu   
Principal Investigator: Edward Chu, MD         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Yun Yen City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01666756     History of Changes
Other Study ID Numbers: 11043, NCI-2012-01324, 5P01CA154295-02
Study First Received: August 14, 2012
Last Updated: June 11, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014