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

This study has been completed.
Sponsor:
Collaborator:
PharmaNet
Information provided by (Responsible Party):
Golden Biotechnology Corporation
ClinicalTrials.gov Identifier:
NCT01134016
First received: May 14, 2010
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Antroquinonol
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Golden Biotechnology Corporation:

Primary Outcome Measures:
  • 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



Secondary Outcome Measures:
  • 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 ]
    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)


Enrollment: 13
Study Start Date: December 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

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.
  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01134016

Locations
Taiwan
Tri-Service General Hospital
Taipei, Taiwan, 11490
Taipei Veterans General Hospital
Taipei, Taiwan, 201
Sponsors and Collaborators
Golden Biotechnology Corporation
PharmaNet
Investigators
Principal Investigator: Woei-Yau Kao, M.D. Tri-Service General Hospital
Principal Investigator: Yu-Chin Lee, M.D. Taipei Veterans General Hospital, Taiwan
  More Information

No publications provided

Responsible Party: Golden Biotechnology Corporation
ClinicalTrials.gov Identifier: NCT01134016     History of Changes
Other Study ID Numbers: GOLANTA20090911
Study First Received: May 14, 2010
Results First Received: August 12, 2013
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration
Taiwan : Food and Drug Administration

Keywords provided by Golden Biotechnology Corporation:
Lung cancer
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 29, 2014