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 Determind the Maximum Tolerable Dose for Antroquinonol [ Time Frame: DLT is to be observed during 4 week period ] [ Designated as safety issue: Yes ]
The study design consisted of 2 phases, the accelerated titration phase and the standard titration phase.
During the accelerated titration phase, patients were enrolled in a cohort of 1 new patient for each dose level and treated for 4 weeks at that level. Any DLT or instance of MT during any 4 week treatment at any dose level led to the initiation of standard titration (3+3) phase.
If none of the first 3 patients experienced any DLT, then dose escalation proceeded for the next cohort of patients. If 1 of 3 patients developed DLT, the cohort was expanded to at most 6 patients (another 3 patients added subsequently). If exactly 1 of the 6 patients experienced DLT, then escalation to the next dose level occurred. If more than 1 patient developed DLT in any dose cohort, the dose escalation was withheld and the prior dose level was considered as the MTD unless the present dose level was level 1
- 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|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
6 dose levels, Dose Level 1 (4 weeks) : 50 mg Antroquinonol; Dose Level 2 (4 weeks) : 100mg Antroquinonol; Dose Level 3 (4 weeks) : 200mg Antroquinonol; Dose Level 4 (4 weeks) : 300mg Antroquinonol; Dose Level 5 (4 weeks) : 450mg Antroquinonol; Dose Level 6 (4 weeks) : 600mg Antroquinonol.
A maximum of 36 patients were planned based on a criteria of a maximum of 6 patients per cohort: 1 to 6 patients were planned for each dose group in the accelerated phase; 3 to 6 patients for each dose group in the standard phase .
The method of dose escalation in the accelerated titration phase continued to the next higher dose level until a patient experienced MT or a DLT. Standard titration phase start with 3+3 patients. Dose escalation proceeded sequentially between cohorts.
Antroquinonol was taken orally, daily, within 15 minutes after a breakfast at the assigned dose level: 50, 100, 200, 300, 450, 600 mg/day for 4 weeks.
Dose Level 1 (4 weeks) : 50 mg Antroquinonol; Dose Level 2 (4 weeks) : 100mg Antroquinonol; Dose Level 3 (4 weeks) : 200mg Antroquinonol; Dose Level 4 (4 weeks) : 300mg Antroquinonol; Dose Level 5 (4 weeks) : 450mg Antroquinonol; Dose Level 6 (4 weeks) : 600mg Antroquinonol.
The accelerated phase ended when either 1 DLT or MT was observed to start standard phase. Study ended when reach the highest dose level or DLT founded.
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|
|Taipei, Taiwan, 11490|
|Taipei Veterans General Hospital|
|Taipei, Taiwan, 201|
|Principal Investigator:||Woei-Yau Kao, M.D.||Tri-Service General Hospital|
|Principal Investigator:||Yu-Chin Lee, M.D.||Taipei Veterans General Hospital, Taiwan|