Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC

• Sponsor: Golden Biotechnology Corporation
• Collaborator: ICON Clinical Research
• Information provided by (Responsible Party): Golden Biotechnology Corporation

Study Description

Brief Summary:

This is a single arm, open label, Phase II study in KRAS-positive and KRAS-negative patients with stage IV (including pleural effusion) non squamous NSCLC who have failed two lines of anti-cancer therapy. A maximum of 60 evaluable patients with NSCLC will receive antroquinonol, of which 30 patients will be KRAS-positive and 30 patients KRAS-negative. An evaluable patient will have received at least one dose of antroquinonol and have a valid baseline tumor assessment. Enrollment will continue until the target number of evaluable patients has been enrolled.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer Stage IV	Drug: Antroquinonol	Phase 2

Detailed Description:

1. Progression free survival rate at 12 weeks, defined as the proportion of patients alive and progression free at Week 12. Patients will be progression free if they have no tumor assessments of progressive disease (defined according to RECIST guidelines, version 1.1) at any point from the start of treatment to Week 12.
2. Objective response rate (ORR), defined as the proportion of patients whose best overall response is either CR or PR according to RECIST version 1.1. The best overall response is the best response recorded during the first 12 week treatment cycle.
3. Disease control rate (DCR), defined as the proportion of patients with a documented CR, PR and SD during the first 12 week treatment cycle according to RECIST version 1.1.
4. Duration of overall tumor response (DR), defined as the interval between the date of the first observation of tumor response (CR or PR) and the date of disease progression or death.
5. Progression free survival defined as the time from randomization to objective tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first.
6. Overall survival (OS) defined as the time from randomization to death from any cause.
7. Time to progression (TTP) defined as the time from randomization to objective tumor progression by RECIST version 1.1.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	60 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Single-Arm, Open-Label, Phase II Trial Evaluating the Efficacy, Safety and Pharmacokinetics of Antroquinonol in Patients With Stage IV (Including Pleural Effusion) Non Squamous NSCLC Who Have Failed Two Lines of Anti-Cancer Therapy
Study Start Date :	October 2013
Estimated Primary Completion Date :	January 2019
Estimated Study Completion Date :	January 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Antroquinonol (Hocena); patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression, unacceptable toxicity, non compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first.	Drug: Antroquinonol; patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression, unacceptable toxicity, non compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first.; Other Name: Hocena

Outcome Measures

Primary Outcome Measures :

1. Progression free survival rate [ Time Frame: 12 weeks ]
   Tumor response will be assessed at 6 week intervals during the first treatment cycle using the RECIST criteria, version 1.1. Each patient will be assigned one of the following categories: 1) complete response (CR), 2) partial response (PR), 3) stable disease (SD), or 4) progressive disease (PD). Patients who died from any cause or discontinued the study for any reason without a post screening or Week 12 tumor assessment will be considered as failing to respond to treatment.

Secondary Outcome Measures :

1. Pharmacokinetic Profiling,Preliminary Efficacy and Safety Tests in T.I.D treatment [ Time Frame: 12 weeks ]

   PK sampling will be performed on Days 0 and 28 in all patients enrolled in Stage 1. Sparse PK sampling will be performed on Days 28, 42, and 56 in all patients enrolled in Stage 2.

   PK endpoints will be derived for intensively sampled PK profiles by non compartmental methods and include:

   Cmax: peak concentration;Ctrough: trough plasma concentration; Tmax: peak time;AUC: area under the plasma concentration time curve over the 8 hour dosing interval;T½: terminal half life;Vz/F: apparent volume of distribution during elimination;CL/F: apparent oral clearance;T½, eff: effective half life.

2. Disease control rate (DCR) [ Time Frame: up to 48 weeks ]
   the proportion of patients with a documented CR, PR and SD during the first 12 week treatment cycle according to RECIST version 1.1.

Other Outcome Measures:

1. Objective response rate (ORR) [ Time Frame: 12 weeks ]
   Dfined as the proportion of patients whose best overall response is either CR or PR according to RECIST version 1.1. The best overall response is the best response recorded during the first 12 week treatment cycle.
2. Overall survival (OS) [ Time Frame: Up to 48 weeks ]
   Defined as the time from randomization to death from any cause.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Cytologically or histologically confirmed non squamous NSCLC Stage IV (including pleural effusion).
• Radiologically confirmed disease progression following two previous lines of anti-cancer therapy, one of which should be a platinum based regimen, OR the patient has refused treatment with approved treatment modalities
• At least one radiologically measurable target lesion per RECIST version 1.1
• Fresh or archival biopsy tissue available to determine tumor mutation status
• Written informed consent that is consistent with International Conference on Harmonisation Tripartite Guideline on Good Clinical Practice guidelines
• Patient or legally acceptable representative has granted written informed consent before any study specific procedures (including special Screening tests) are performed
• Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2
• Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x 109/L; absolute neutrophil count ≥ 1.5 x 109/L without the use of hematopoietic growth factors
• Bilirubin and creatinine less than 2 × upper limit of normal (ULN) for the institution
• Albumin ≥ 2.5 mg/dL
• Aspartate aminotransferase and alanine aminotransferase less than 5 × ULN for the institution
• Prothrombin time less than 1.5 × ULN for the institution
• Potassium, magnesium and phosphorus within the normal range for the institution (supplementation is permissible)
• Recovery to Grade 1 or baseline of any toxicities due to prior treatments, excluding alopecia

Exclusion Criteria:

• Chemo-, hormone- or immunotherapy, within 4 weeks or within less than four half lives of the date of first administration of study drug and/or persistence of toxicities of prior anti-cancer therapies which are deemed to be clinically relevant
• Radiotherapy within the past 2 weeks prior to date of first administration of study drug
• Previous treatment with an histone deacetylase inhibitor or an epidermal growth factor receptor inhibitor within at least 4 weeks of the date of first administration of study drug
• Treatment with any drug(s) known to be an inhibitor or inducer of cytochrome P450 (CYP)2C19, CYP3A4, CYP2C8, and CYP2E1, within 14 days of the date of first administration of study drug
• Brain metastases, which are symptomatic; patients with treated, brain metastases are eligible with stable brain disease for at least 4 weeks without the requirement for steroids or anti epileptic therapy
• Inability to swallow oral medications or a recent acute gastrointestinal disorder with diarrhea e.g., Cohn's disease, malabsorption, or Common Terminology Criteria for Adverse Event (CTCAE) Grade > 2 diarrhea of any etiology at baseline
• Other malignancies diagnosed within the past five years (other than curatively treated cervical cancer in situ), non melanoma skin cancer, superficial bladder tumors Ta (non invasive tumor) and TIS (carcinoma in situ)
• Patients with any serious active infection (i.e., requiring an intravenous antibiotic, antifungal, or antiviral agent)
• Patients with known human immunodeficiency virus, active hepatitis B or active hepatitis C
• Patients who have any other life threatening illness or organ system dysfunction, which in the opinion of the investigator, would either compromise patient safety or interfere with the evaluation of the safety of the study drug
• Known or suspected substance abuse or alcohol abuse
• Pregnancy or breast feeding
• History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association functional classification of three

Contacts and Locations

Locations

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United States, Arizona
Arizona Clinical Research Center	Recruiting
Tucson, Arizona, United States, 85715
Contact: Patricia Plezia 520-290-2510
Principal Investigator: Natalie Stanton, M.D.
United States, California
UCSF	Suspended
San Francisco, California, United States, 94115
United States, Illinois
Rush University Medical Center	Terminated
Chicago, Illinois, United States, 60612
United States, Maryland
John Hopkins University	Recruiting
Baltimore, Maryland, United States, 21287
Contact: angela liggins 410-955-8847
Principal Investigator: David Ettinger, M.D.
Peninsula Regional Med Center	Terminated
Salisbury, Maryland, United States, 21801
United States, Michigan
Henry Ford health system	Terminated
Detroit, Michigan, United States, 48202
United States, Pennsylvania
Guthrie Clinic, Ltd	Terminated
Sayre, Pennsylvania, United States, 18840
Taiwan
Chang Gung Memorial Hospital-Kaohsiung medical center	Recruiting
Kaohsiung, Taiwan, 88301
Contact: Chin-Chou Wang, M.D Ph.D. 886-7-7317123
Contact: Yu-Fen Chien 886-7-7317123
National Cheng Kung University Hospitail	Recruiting
Tainan, Taiwan, 704
Contact: Shang-Yin Wu, M.D. 886-6-2353535
Contact: Szu-Wei Hunag 886-6-2353535 ext 3974
Tri Service General Hospital	Recruiting
Taipei, Taiwan
Contact: Ching-Liang Ho +886 2 879 7208
Principal Investigator: Ching-Liang Ho, M.D.

Sponsors and Collaborators

Golden Biotechnology Corporation

ICON Clinical Research

Investigators

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Study Director:	Howard Cheng, Ph.D.	Golden Biotechnology Corp.

More Information

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Responsible Party:	Golden Biotechnology Corporation
ClinicalTrials.gov Identifier:	NCT02047344 History of Changes
Other Study ID Numbers:	GHNSCLC-2 001
First Posted:	January 28, 2014
Last Update Posted:	August 17, 2017
Last Verified:	August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided
Plan Description:	need DMC proved

Keywords provided by Golden Biotechnology Corporation:

NSCLC

Additional relevant MeSH terms:

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Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms	Lung Diseases; Respiratory Tract Diseases; Ubiquinone; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs