Clinical trial NCT01134016: Determine MTD and to Evaluate pk, Safety/Tolerability and Efficacy Profiles of Hocena® in NSCLC Subjects
Official title: Determine MTD and to Evaluate PK, Safety/Tolerability and Efficacy Profiles of Antroquinonol (Hocena®) in NSCLC Patients Refractory to Conventional Treatment Modalities
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: Lung cancer
NSCLC
Lead sponsor: Golden Biotechnology Corporation
Sponsor class: INDUSTRY
Collaborators: name: PharmaNet
First posted: 2010-05-31
Enrollment: 13
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase I study to determine the maximum tolerable dose (MTD) and to evaluate pharmacokinetic, safety/tolerability and efficacy profiles of antroquinonol (Hocena®) in non-small cell lung cancer (NSCLC) subjects refractory to conventional treatment modalities

Detailed description: 1. Antroquinonol, a novel cyclohexenone compound, is a purified compound from extract of Antrodia camphorata.
2. The pharmacological effects of antroquinonol were postulated to exert its antitumorigenesis effects through interactions to primary targets of epidermal growth factor receptor (EGFR)/Akt/mitogen-activated protein kinase (MAPK).
3. In vivo study in NOD/SCID mice with A549 subcutaneous xenografts consistently showed tumor growth suppression after 2 weeks of oral 30 and 60 mg/kg antroquinonol treatment.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 20 years.
2. Diagnosed stage III/IV NSCLC. The grading is determined according to the Tumor-Node-Metastasis (TNM) staging system for lung cancer.
3. Patients with histologically or cytologically proven primary NSCLC with adenocarcinoma or mixed cell type with adenocarcinoma, who have failed on standard treatments.
4. With progressive tumor after two lines of chemotherapy (including one platinum-based) and 1 EGFR-targeted therapy if patient is identified with EGFR mutation or his/her EGFR mutation status is unknown OR having refused further currently approved treatment modalities.
5. Life expectancy ≥ 3 months.
6. Within 1 week of planned first study treatment day, adequate hematopoietic functions are presented: Total white blood cell (WBC) ≥ 3500 cells/mm3 Hemoglobin (Hb) ≥ 9.0 g/dL Platelets ≥ 100,000 cells/mm3 Absolute neutrophil count (ANC) ≥ 1500 /mm3
7. Within 1 week of planned first study treatment day, adequate hepatic and renal functions are presented: Total bilirubin ≤2.0 mg/dLGOLANTA20090911, Amendment 4/v. 1.0/ 13 October 2010 AST ≤ 3 × upper limit of normal (ULN); patients with liver metastasis: AST ≤ 5 × ULN ALT ≤ 3 × ULN; patients with liver metastasis: ALT ≤ 5 × ULN Creatinine ≤ 1.5 mg/dL
8. Must have recovered from toxicities of previous anti-cancer treatments to grade 1 NCI-CTC or better, except for alopecia.
9. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
10. Female patient with childbearing potential confirmed of not being pregnant at the screening; and informed that effective contraception must be used during the entire treatment period of this study and for 6 months after exiting from the study.
11. Given signed and dated written informed consent form.

Exclusion Criteria:

1. Primary major surgery \< 4 weeks prior to the planned first study treatment day.
2. Lactating, pregnant or plans to be become pregnant.
3. Except for alopecia, recovered from any previous treatments to a grade 1 or less prior to the planned first study treatment day.
4. With active systemic infections, active and clinically significant cardiac diseases, active gastrointestinal ulcers, or medical conditions that may significantly affect adequate absorption of investigational product.
5. Within 5 years, prior history of malignancy other than NSCLC, except cervical carcinoma in situ and basal or squamous cell skin carcinoma.
6. Known allergic to antroquinonol or its formulation excipients.
7. Within 14 days of planned first study treatment day, exposed to any drug(s) known to be significant CYP2C19, 3A4, 2C8, and 2E1, inhibitor or activator.
8. With conditions judged by the investigator as unsuitable for the study.

Primary outcomes:
measure: To Determind the Maximum Tolerable Dose for Antroquinonol
timeFrame: DLT is to be observed during 4 week period
Secondary outcomes:
measure: Tmax After Dose
timeFrame: 30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 1&28
measure: Half-life Time From Overall Study
timeFrame: 30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 1&28
measure: Maximum Plasma Concentration After on Day 1
timeFrame: 30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 1
measure: Maximum Plasma Concentration After Dosing on Day 28
timeFrame: 30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 28
measure: AUC0-t on Day 1
timeFrame: within 30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 1
measure: AUC0-t on Day 28
timeFrame: 30 minutes prior to and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 14, and 24 hours after dose of Day 28
measure: Number of Participants in the PP Population With Better Than SD at Target Lesion, Better Than Non-CR/Non-PD at Non-target Lesion and no New Lesion
timeFrame: pre-screening and end of treatment
measure: Safety Blood and Urine Test
timeFrame: pre-screenting and every 14-day period
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Tri-Service General Hospital
name: Woei-Yau Kao, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Taipei Veterans General Hospital, Taiwan
name: Yu-Chin Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
References: