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

NCT01134016 | Completed Phase 1 Results DMC

• 1 other identifier: GOLANTA20090911
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

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

Conditions

Non-small Cell Lung Cancer

Keywords

Lung cancer; NSCLC

Outcome Measures

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

  DLT is to be observed during 4 week period

Secondary Outcomes (8)

• Tmax After Dose

  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

• Half-life Time From Overall Study

  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

• Maximum Plasma Concentration After on Day 1

  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

• Maximum Plasma Concentration After Dosing on Day 28

  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

• AUC0-t on Day 1

  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

Study Arms (1)

Antroquinonol

EXPERIMENTAL

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

Antroquinonol DRUG

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

Antroquinonol

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Golden Biotechnology Corporation: lead
• PharmaNet: collaborator

Study Sites (2)

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 201, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

antroquinonol

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Howard Cheng, Director of clinical trials
• Organization: Golden Biotechnology Corp.

howard@goldenbiotech.com.tw

886-2808-6006

Study Officials

• Woei-Yau Kao, M.D.

  Tri-Service General Hospital

  PRINCIPAL INVESTIGATOR

• Yu-Chin Lee, M.D.

  Taipei Veterans General Hospital, Taiwan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2010
• First Posted: May 31, 2010
• Study Start: December 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 21, 2016
• Results First Posted: February 27, 2014

Record last verified: 2014-11

Data Sharing

• IPD Sharing: Will not share

Locations

TW (2)