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

NCT01666756 | Completed Phase 1 DMC

• 3 other identifiers: 11043NCI-2012-013245P01CA154295-02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  28 days

Secondary Outcomes (6)

• Adverse events as determined by NCI CTCAE version 4

  Up to 4 weeks after completion of study treatment

• Serious adverse events as determined by NCI CTCAE version 4

  Up to 4 weeks after completion of study treatment

• Discontinuation rate

  Up to 6 years

• Dose adjustment rate

  Up to 6 years

• Tumor response in terms of best overall response, assessed using RECIST

  Up to 6 years

Other Outcomes (2)

• Change in cytokine/chemokine levels

  Baseline to up to 6 years

• Change in levels of soluble biomarkers

  Baseline to up to 6 years

Study Arms (1)

Treatment (Chinese herbal formulation PHY906 and sorafenib)

EXPERIMENTAL

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; Drug: sorafenib tosylate; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

Chinese herbal formulation PHY906 DIETARY_SUPPLEMENT

Given PO

Also known as: PHY-906, KD018

Treatment (Chinese herbal formulation PHY906 and sorafenib)

sorafenib tosylate DRUG

Given PO

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

Treatment (Chinese herbal formulation PHY906 and sorafenib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (Chinese herbal formulation PHY906 and sorafenib)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (Chinese herbal formulation PHY906 and sorafenib)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 cycle 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

PHY 906; Sorafenib

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

Study Officials

• Joseph Chao, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2012
• First Posted: August 16, 2012
• Study Start: June 11, 2014
• Primary Completion: May 29, 2020
• Study Completion: May 29, 2020
• Last Updated: January 27, 2021

Record last verified: 2021-01

Locations

US (1)