Study of Botanical PHY906 Plus Capecitabine for Advanced Unresectable Hepatocellular Carcinoma

NCT00076609 | Completed Phase 1

• 1 other identifier: PHY906-2002-1
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 5

Brief Summary

Capecitabine is a chemotherapeutic that has been approved for use in breast and colorectal cancers. The advantages of capecitabine are that (1) it is an oral drug; and (2) it is less toxic than many other chemotherapeutics. In an off-label hepatocellular carcinoma (HCC) clinical study, the response rate with capecitabine was 13%. The botanical drug PHY906--currently manufactured pursuant to GMP standards and regulations--has been used in China for over 1800 years to treat gastrointestinal-related ailments. Recently, preclinical studies demonstrated that PHY906 potentiates the anti-tumor effect of capecitabine. This trial will evaluate the safety and efficacy of PHY906 in enhancing the anti-tumor effects of capecitabine.

Conditions

Hepatocellular Carcinoma; Liver Cancer

Keywords

hepatocellular carcinoma; advanced; unresectable; liver cancer; systemic chemotherapy; botanical; herbal; alternative and complementary medicine; capecitabine; PHY906; oral; HCC; traditional chinese medicine; tcm; QOL; quality of life

Outcome Measures

Primary Outcomes (2)

• Tumor imaging and evaluation every 6 weeks

• Alphafetoprotein measurements every 3 weeks for first 3 courses, then every 6 weeks thereafter

Secondary Outcomes (2)

• QoL assessment every 3 weeks

• Survival follow-up every 2 months

Interventions

PHY906 DRUG

capecitabine DRUG

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women 18 to 80 years of age with a histologic or cytologic diagnosis of HCC or who meet all of the following criteria: (a) a-fetoprotein levels \> 600 ng/mL; and (b) presence of cirrhosis or chronic hepatitis B or C; and (c) characteristic enhancement pattern of liver tumors on triphasic CT scan or MRI.

You may not qualify if:

• In the phase I (dose finding) and phase II (efficacy) portions of the study, patients may either have had no prior chemotherapy (chemotherapy naive), no prior capecitabine chemotherapy, or have been refractory to--or relapsed from--no more than two prior systemically administered treatment regimens. (Chemoembolization is not regarded in this context as a systemically administered treatment regimen.)
• All patients in both the phase I and phase II portions of this study must have at least one previously unirradiated, bidimensionally measurable lesion by computerized tomography (CT) or magnetic resonance imaging (MRI) scan of \> 20 mm (if conventional CT scan) or more than or equal to 10 mm (if spiral CT scan). Triphasic spiral CT or MRI scans are preferred when such equipment is available. All CT scans should employ a "hepatoma protocol" image capture technique.
• Patients with central nervous system (CNS) involvement will have had appropriate treatment and will be free of progressive neurological deficits in the 28 days prior to enrollment.
• Patients with cirrhosis must have a Child-Pugh cirrhosis severity classification no greater than B.
• Baseline performance status must be Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2.
• Life expectancy must be reasonably estimated to be \> 12 weeks.
• Women patients who are known to be capable of conception should have a negative serum pregnancy test (beta-human chorionic gonadotropin \[b-hCG\]) within 2 weeks of starting the study; all patients should agree to use adequate non-estrogenic birth control methods, consistent with the institute's standard form of contraception if conception is possible during the study.
• Provide written informed consent prior to screening.
• Patients with an estimated (Cockroft and Gault equation) to the power of 40 or calculated baseline creatinine clearance of 30-50 mL/min should have the starting dose of capecitabine reduced to 750 mg/m2 BID X 14 days; the dose of PHY906 remains unchanged. Patients with a baseline creatinine clearance of less than 30 mL/min should not be enrolled in this trial.
• Patients with Child-Pugh cirrhosis severity classification of C.
• Baseline abnormalities in hepatic tests (AST \> 5.0 X study center upper limit of normal (ULN); ALT \> 5.0 X study center ULN; albumin \< 2.8 g/dL; international normalized ratio for prothrombin time (INR) \> 1.5 X study center ULN; total bilirubin \> 3.0 x study center ULN).
• Baseline hemoglobin \< 10.0 g/dL; total WBC \< 2.0 X 10 to the power of 9/L; absolute neutrophil count (ANC) \< 1.0 X 10 to the power of 9/L; or platelet count \< 50.0 X 10 to the power of 9/L.
• Patients who are pregnant or breastfeeding.
• Any prior radiation therapy (other than small portals used for the palliation of isolated, symptomatic, osseous metastases) must have been completed more than 21 days before entry into the study and evaluable lesions must not have been included in the radiation portal.
• Patients may be either treatment naive or have had previous anticancer treatment; if previously treated they may not have been exposed to capecitabine and no more than two prior systemically administered treatment regimens are allowed. It is required that all treatment be completed no less than 21 days prior to the patient being treated in this study. Chemoembolization or hepatic resection are not regarded as systemically administered treatment regimens.

Sponsors & Collaborators

• PhytoCeutica: lead

Study Sites (5)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

VA Connecticut Cancer Center

West Haven, Connecticut, 06516, United States

Location

National Institute of Cancer Research

Taipei, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

PHY 906; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 27, 2004
• First Posted: January 28, 2004
• Study Start: October 1, 2003
• Last Updated: March 28, 2007

Record last verified: 2007-03

Locations

TW (1); US (4)