Determine MTD and to Evaluate pk, Safety/Tolerability and Efficacy Profiles of Hocena® in NSCLC Subjects
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
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Determine MTD and to Evaluate PK, Safety/Tolerability and Efficacy Profiles of Antroquinonol (Hocena®) in NSCLC Patients Refractory to Conventional Treatment Modalities|
- To determine MTD and dose limiting toxicities (DLTs) of antroquinonol [ Time Frame: DLT is to be observed during 4 week period ] [ Designated as safety issue: Yes ]
There are two phases in this study, the accelerated titration phase and the standard titration phase.
MT is defined as any grade 2 toxicity and DLT is defined as any grade 3 or above toxicity by the National Cancer Institute (NCI)Common Terminology Criteria for Adverse Event (CTCAE) version 4.03 as determined by the investigator to be at least possibly related in causality to the treatment. Nausea, vomiting and diarrhea of grade 3 or more are to be counted as DLT only if they remain at grade 3 or more despite adequate treatment.
- Pharmacokinetic profiling,Preliminary Efficacy and safety tests [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Pharmacokinetic samples will be obtained from all the patients in each dose cohort treated in all phases of the study. Patients will only be sampled during their first treatment cycle only. Pharmacokinetic sampling will occur as follows:
Day 1 &28: (Approximate 5 mL per sample, 60 mL in total) 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&28.
Trough blood sampling will be collected right before dosing of study treatment on Day 14 and Day 27.
- Preliminary Efficacy [ Time Frame: pre-screening and end of treatment ] [ Designated as safety issue: Yes ]Changes in measurable tumor size measured according to RECIST version 1.
- Safety blood and Urine test [ Time Frame: pre-screenting and every 14-day period ] [ Designated as safety issue: Yes ]
- Hematology laboratory data
- Biochemistry laboratory data
- AE; AE not including the natural progress of the underlying disease
- Incidence of toxicity ≥ grade 3 according to NCI CTCAE version 4.03
- Physical examination
- Vital signs changes
- Electrocardiogram examination results (including HR, QRS, QT, QTc, RR intervals)
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||June 2013|
|Estimated Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Safety dose finding from 50mg to 600mg
Dosage form: 50 mg and 100 mg capsules
Dosage levels: 50 mg, 100 mg, 200 mg, 300mg, 450mg and 600mg ( 6 cohorts)
Frequency: take daily for 4 weeks per subject per dosage level
Other Name: Hocena
- Antroquinonol, a novel cyclohexenone compound, is a purified compound from extract of Antrodia camphorata.
- 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).
- 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.
|Tri-Service General Hospital||Recruiting|
|Taipei, Taiwan, 11490|
|Contact: Ching-Liang Ho, M.D. 886-2-87923311|
|Principal Investigator: Ching-Liang Ho, M.D.|
|Taipei Veterans General Hospital||Recruiting|
|Taipei, Taiwan, 201|
|Contact: Yu-Chin Lee, M.D. 886-2-28712121|
|Principal Investigator: Yu-Chin Lee, M.D.|
|Principal Investigator:||Woei-Yau Kao, M.D.||Tri-Service General Hospital|
|Principal Investigator:||Yu-Chin Lee, M.D.||Taipei Veterans General Hospital, Taiwan|