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CompletedNCT01134016HocenaUpdated Jun 21, 2016Results posted

Determine MTD and to Evaluate pk, Safety/Tolerability and Efficacy Profiles of Hocena® in NSCLC Subjects

A Phase 1 interventional study of Antroquinonol in Non-small Cell Lung Cancer, sponsored by Golden Biotechnology Corporation. Completed at 2 sites in Taiwan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2016-06-21.

Sponsored by Golden Biotechnology Corporation · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
13
Allocation
Not applicable
Ages
20 Years and older
Sex
All
01

Study 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

Read the 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.
02

Conditions studied

  • Non-small Cell Lung Cancer

Keywords

  • Lung cancer
  • NSCLC
03

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 13 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

Golden Biotechnology Corporation is the lead sponsor of 9 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
13 participants (actual)

Study arms

  • Experimental
    Antroquinonol

    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.

    Drug: Antroquinonol

Interventions

  • DrugAntroquinonol

    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.

    Also known as: Hocena

06

What researchers measure

Primary outcomes

  1. To Determind the Maximum Tolerable Dose for Antroquinonol

    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

    Time frame: DLT is to be observed during 4 week period

Secondary outcomes

  1. Tmax After Dose

    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. Individual serum concentration versus (vs) time curves were plotted in 1 graph by dose level on both linear/linear and log10/linear scales. Mean serum concentration vs time curves were also presented in 1 graph for dose levels on both linear/linear and log10/linear scales.

    Time frame: 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

  2. Half-life Time From Overall Study

    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. Individual serum concentration versus (vs) time curves were plotted in 1 graph by dose level on both linear/linear and log10/linear scales. Mean serum concentration vs time curves were also presented in 1 graph for dose levels on both linear/linear and log10/linear scales.

    Time frame: 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

  3. Maximum Plasma Concentration After on Day 1

    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.

    Time frame: 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

  4. Maximum Plasma Concentration After Dosing on Day 28

    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.

    Time frame: 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

  5. AUC0-t on Day 1

    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.

    Time frame: 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

  6. AUC0-t on Day 28

    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.

    Time frame: 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

  7. 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

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for overall response by CT: Judgement by total siutation of target, non-target and new lesions. Meaning of Target lesion: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), Sum down 30% or more from target lesion baseline; Progressive Disease(PD), Sum up at least 20% from smallest value (nadir) and Absolute increase ≥ 5 mm; Stable Disease (SD), Neither enough shrinkage for PR nor enough growth for PD. non-target lesion: CR: All non-target lesions disappeared and All lymph nodes \<10 mm; Non-CR/Non-PD: Non-target lesion(s) still present and Lymph nodes ≥10 mm; PD: Unequivocal progression; New lesion :Unequivocal new cancer lesions Overall SD response should be better than SD at target lesion, better than Non-CR/Non-PD t non-target lesion and no new lesion.

    Time frame: pre-screening and end of treatment

  8. Safety Blood and Urine Test

    1. Hematology laboratory data 2. Biochemistry laboratory data 3. Urinalysis 4. AE; AE not including the natural progress of the underlying disease 5. Incidence of toxicity ≥ grade 3 according to NCI CTCAE version 4.03 6. Physical examination 7. Vital signs changes 8. Electrocardiogram examination results (including HR, QRS, QT, QTc, RR intervals)

    Time frame: pre-screenting and every 14-day period

07

Results

Posted Feb 27, 2014

Participant flow

A total of 13 patients were enrolled and treated: 1 patient each received 50, 100, 200, and 300 mg, 4 patients received 450 mg, and 5 patients received 600 mg. The recruitment period is from 19 Jan 2010 to 13 Dec 2012 in list two medical center, Taiwan.

Participant flow — Overall Study
MilestoneAntroquinonol
Started13
Completed10
Not completed3

Outcome measures

PrimaryTo Determind the Maximum Tolerable Dose for Antroquinonol

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

Time frame:
DLT is to be observed during 4 week period
Reported as:
Number · mg
To Determind the Maximum Tolerable Dose for Antroquinonol
mgAntroquinonol
To Determind the Maximum Tolerable Dose for Antroquinonol600
SecondaryTmax After Dose

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. Individual serum concentration versus (vs) time curves were plotted in 1 graph by dose level on both linear/linear and log10/linear scales. Mean serum concentration vs time curves were also presented in 1 graph for dose levels on both linear/linear and log10/linear scales.

Time frame:
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
Reported as:
Median · hours
Tmax After Dose
hoursTmax Day1: 50mgTmax Day 1: 100 mgTmax Day 1: 200mgTmax Day 1: 300mgTmax Day 1: 450mgTmax Day 1 :600 mgTmax Day 28: 50mgTmax Day 28: 100mgTmax Day 28: 200 mgTmax Day 28: 300mgTmax Day 28: 450mgTmax Day 28: 600mg
Tmax After Dose2.00 (2.00 to 2.00)1.00 (1.00 to 1.00)10.00 (10.00 to 10.00)1.13 (1.13 to 1.13)1.82 (1.08 to 3.97)3.70 (2.00 to 9.70)1.92 (1.92 to 1.92)3.17 (3.17 to 3.17)4.00 (4.00 to 4.00)4.05 (4.05 to 4.05)3.00 (1.07 to 6.20)3.15 (2.07 to 3.87)
SecondaryHalf-life Time From Overall Study

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. Individual serum concentration versus (vs) time curves were plotted in 1 graph by dose level on both linear/linear and log10/linear scales. Mean serum concentration vs time curves were also presented in 1 graph for dose levels on both linear/linear and log10/linear scales.

Time frame:
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
Reported as:
Mean · hours
Half-life Time From Overall Study
hoursHalf-life Time Day 1:50mgHalf-life Time Day 1: 100 mgHalf-life Time Day 1: 200mgHalf-life Time Day 1: 300mgHalf-life Time Day 1: 450 mgHalf-life Time Day 1: 600 mgHalf-life Time Day 28: 50mgHalf-life Time Day 28:100 mgHalf-life Time Day 28: 200 mgHalf-life Time Day 28: 300 mgHalf-life Time Day 28: 450 mgHalf-life Time Day 28: 600mg
Half-life Time From Overall Study2.421.304.331.932.38 ± 1.343.07 ± 1.521.602.341.412.111.81 ± 0.662.55 ± 1.30
SecondaryMaximum Plasma Concentration After on Day 1

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.

Time frame:
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
Reported as:
Mean · Log(mg/ml)
Maximum Plasma Concentration After on Day 1
Log(mg/ml)Cmax Day 1
Maximum Plasma Concentration After on Day 10.504 (0.17 to 0.83)
SecondaryMaximum Plasma Concentration After Dosing on Day 28

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.

Time frame:
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
Reported as:
Mean · log(mg/ml)
Maximum Plasma Concentration After Dosing on Day 28
log(mg/ml)Cmax Day 28
Maximum Plasma Concentration After Dosing on Day 280.682 (0.08 to 1.28)
SecondaryAUC0-t on Day 1

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.

Time frame:
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
Reported as:
Mean · log(mg*hr/mL)
AUC0-t on Day 1
log(mg*hr/mL)AUC0-t on Day 1
AUC0-t on Day 10.641 (0.16 to 1.12)
SecondaryAUC0-t on Day 28

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.

Time frame:
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
Reported as:
Mean · log(mg*hr/mL)
AUC0-t on Day 28
log(mg*hr/mL)AUC0-t on Day 28
AUC0-t on Day 280.957 (0.59 to 1.32)
SecondaryNumber 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

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for overall response by CT: Judgement by total siutation of target, non-target and new lesions. Meaning of Target lesion: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), Sum down 30% or more from target lesion baseline; Progressive Disease(PD), Sum up at least 20% from smallest value (nadir) and Absolute increase ≥ 5 mm; Stable Disease (SD), Neither enough shrinkage for PR nor enough growth for PD. non-target lesion: CR: All non-target lesions disappeared and All lymph nodes \<10 mm; Non-CR/Non-PD: Non-target lesion(s) still present and Lymph nodes ≥10 mm; PD: Unequivocal progression; New lesion :Unequivocal new cancer lesions Overall SD response should be better than SD at target lesion, better than Non-CR/Non-PD t non-target lesion and no new lesion.

Time frame:
pre-screening and end of treatment
Reported as:
Number · participants
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
participantsTumer Responce at Per-protocol (PP) Population
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 Lesion3
SecondarySafety Blood and Urine Test

1. Hematology laboratory data 2. Biochemistry laboratory data 3. Urinalysis 4. AE; AE not including the natural progress of the underlying disease 5. Incidence of toxicity ≥ grade 3 according to NCI CTCAE version 4.03 6. Physical examination 7. Vital signs changes 8. Electrocardiogram examination results (including HR, QRS, QT, QTc, RR intervals)

Time frame:
pre-screenting and every 14-day period

Results for this outcome have not been posted.

Adverse events

Collected over recorded immediatly as AE happen. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Antroquinonol—0/13 (0%)13/13 (100%)
Most frequent other events
Most frequent other events
EventAntroquinonol
diarrheaGastrointestinal disorders12/13
vomitingGastrointestinal disorders9/13
nauseaGastrointestinal disorders7/13

Baseline characteristics

A total of 13 patients were enrolled in this study

Age, Categorical
Age, Categorical(Participants)Antroquinonol
<=18 years0
Between 18 and 65 years7
>=65 years6
Sex: Female, Male
Sex: Female, Male(Participants)Antroquinonol
Female6
Male7
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Antroquinonol
American Indian or Alaska Native0
Asian13
Native Hawaiian or Other Pacific Islander0
Black or African American0
White0
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Antroquinonol
Taiwan13
Height
Height(cm)Antroquinonol
Mean159.76 (143 to 172)
Weight
Weight(Kg)Antroquinonol
Mean64.57 (45.7 to 79.2)
BMI
BMI(kg/m^2)Antroquinonol
Mean25.214 (21.15 to 32.97)
08

Study locations

2 sites
  • Tri-Service General Hospital
    Taipei, 11490, Taiwan
  • Taipei Veterans General Hospital
    Taipei, 201, Taiwan
09

References and documents

Individual participant data

Plan to share: No — There is not a plan to make individual participlant data(IPD).

No publications or documents are linked to this record.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 21, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01134016
Lead sponsor
Golden Biotechnology Corporation
Collaborators
PharmaNet
Responsible party
Sponsor
First posted
May 31, 2010
Start date
Dec 2010
Primary completion
Jun 2013
Completion
Jun 2013
Results posted
Feb 27, 2014
Last update
Jun 21, 2016

Study contacts

Woei-Yau Kao, M.D.
principal investigator · Tri-Service General Hospital
Yu-Chin Lee, M.D.
principal investigator · Taipei Veterans General Hospital, Taiwan

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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