- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01134016
Determine MTD and to Evaluate pk, Safety/Tolerability and Efficacy Profiles of Hocena® in NSCLC Subjects (Hocena)
Determine MTD and to Evaluate PK, Safety/Tolerability and Efficacy Profiles of Antroquinonol (Hocena®) in NSCLC Patients Refractory to Conventional Treatment Modalities
Study Overview
Detailed Description
- 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Taipei, Taiwan, 11490
- Tri-Service General Hospital
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Taipei, Taiwan, 201
- Taipei Veterans General Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 20 years.
- Diagnosed stage III/IV NSCLC. The grading is determined according to the Tumor-Node-Metastasis (TNM) staging system for lung cancer.
- Patients with histologically or cytologically proven primary NSCLC with adenocarcinoma or mixed cell type with adenocarcinoma, who have failed on standard treatments.
- 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.
- Life expectancy ≥ 3 months.
- 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
- 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
- Must have recovered from toxicities of previous anti-cancer treatments to grade 1 NCI-CTC or better, except for alopecia.
- Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
- 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.
- Given signed and dated written informed consent form.
Exclusion Criteria:
- Primary major surgery < 4 weeks prior to the planned first study treatment day.
- Lactating, pregnant or plans to be become pregnant.
- Except for alopecia, recovered from any previous treatments to a grade 1 or less prior to the planned first study treatment day.
- 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.
- Within 5 years, prior history of malignancy other than NSCLC, except cervical carcinoma in situ and basal or squamous cell skin carcinoma.
- Known allergic to antroquinonol or its formulation excipients.
- 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.
- With conditions judged by the investigator as unsuitable for the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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. |
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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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To Determind the Maximum Tolerable Dose for Antroquinonol
Time Frame: DLT is to be observed during 4 week period
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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 |
DLT is to be observed during 4 week period
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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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
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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
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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.
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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
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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
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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.
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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
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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
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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.
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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
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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
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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.
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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
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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
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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.
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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
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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
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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. |
pre-screening and end of treatment
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Safety Blood and Urine Test
Time Frame: pre-screenting and every 14-day period
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pre-screenting and every 14-day period
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Woei-Yau Kao, M.D., Tri-Service General Hospital
- Principal Investigator: Yu-Chin Lee, M.D., Taipei Veterans General Hospital, Taiwan
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GOLANTA20090911
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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