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Trial record 9 of 9 for:    antroquinonol

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

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ClinicalTrials.gov Identifier: NCT01134016
Recruitment Status : Completed
First Posted : May 31, 2010
Results First Posted : February 27, 2014
Last Update Posted : June 21, 2016
Sponsor:
Collaborator:
PharmaNet
Information provided by (Responsible Party):
Golden Biotechnology Corporation

Tracking Information
First Submitted Date  ICMJE May 14, 2010
First Posted Date  ICMJE May 31, 2010
Results First Submitted Date  ICMJE August 12, 2013
Results First Posted Date  ICMJE February 27, 2014
Last Update Posted Date June 21, 2016
Study Start Date  ICMJE December 2010
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2014)
To Determind the Maximum Tolerable Dose for Antroquinonol [ Time Frame: DLT is to be observed during 4 week period ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: May 28, 2010)
To determine MTD and dose limiting toxicities (DLT) [ Time Frame: DLT is to be observed during 4 week period ]
To observe if any grade 3 or above toxicity by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 4.02 as determined by the investigator to be at least possibly related in causality to the IP administration.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
  • Tmax After Dose [ 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 ]
    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.
  • Half-life Time From Overall Study [ 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 ]
    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.
  • Maximum Plasma Concentration After on Day 1 [ 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 ]
    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.
  • Maximum Plasma Concentration After Dosing on Day 28 [ 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 ]
    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.
  • AUC0-t on Day 1 [ 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 ]
    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.
  • AUC0-t on Day 28 [ 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 ]
    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.
  • 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 [ Time Frame: pre-screening and end of treatment ]
    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.
  • Safety Blood and Urine Test [ Time Frame: pre-screenting and every 14-day period ]
    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)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2010)
Pharmacokinetic profiling [ Time Frame: 4 weeks ]
  1. Safety profile:
    • Adverse event incidence
    • Hematology laboratory data changes
    • Biochemistry laboratory data changes
    • Changes in urinalysis
    • Physical examination result changes
    • Incidence of subjects experiencing toxicity ³ grade 3 according to NCI-CTCAE version 4.02
    • Vital signs changes
    • Electrocardiogram (ECG) results (including PR, QRS, QT, QTc, RR intervals)
  2. Efficacy endpoints will be:
    • Changes in measurable tumor size measured according to RECIST version 1.l
    • Changes in quality of life assessed with EORTC QLQ-C30 and LC13
  3. Changes in TRACP 5a
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Determine MTD and to Evaluate pk, Safety/Tolerability and Efficacy Profiles of Hocena® in NSCLC Subjects
Official Title  ICMJE Determine MTD and to Evaluate PK, Safety/Tolerability and Efficacy Profiles of Antroquinonol (Hocena®) in NSCLC Patients Refractory to Conventional Treatment Modalities
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE Drug: Antroquinonol

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
Study Arms  ICMJE 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.

Intervention: Drug: Antroquinonol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 10, 2014)
13
Original Estimated Enrollment  ICMJE
 (submitted: May 28, 2010)
18
Actual Study Completion Date  ICMJE June 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01134016
Other Study ID Numbers  ICMJE GOLANTA20090911
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is not a plan to make individual participlant data(IPD).
Responsible Party Golden Biotechnology Corporation
Study Sponsor  ICMJE Golden Biotechnology Corporation
Collaborators  ICMJE PharmaNet
Investigators  ICMJE
Principal Investigator: Woei-Yau Kao, M.D. Tri-Service General Hospital
Principal Investigator: Yu-Chin Lee, M.D. Taipei Veterans General Hospital, Taiwan
PRS Account Golden Biotechnology Corporation
Verification Date November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP