Clinical Trials /

Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC

NCT02047344

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GHNSCLC-2 001
  • NCT ID: NCT02047344

Conditions

  • Non-small Cell Lung Cancer Stage IV

Interventions

DrugSynonymsArms
AntroquinonolHocenaAntroquinonol (Hocena)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Antroquinonol (Hocena)Experimentalpatients 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.
  • Antroquinonol

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival rate
Time Frame:12 weeks
Safety Issue:
Description: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

Measure:Pharmacokinetic Profiling,Preliminary Efficacy and Safety Tests in T.I.D treatment
Time Frame:12 weeks
Safety Issue:
Description: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.
Measure:Disease control rate (DCR)
Time Frame:up to 48 weeks
Safety Issue:
Description:the proportion of patients with a documented CR, PR and SD during the first 12 week treatment cycle according to RECIST version 1.1.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Golden Biotechnology Corporation

Trial Keywords

  • NSCLC

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