Clinical Trials /

Pacritinib in Patients With Endothelial Growth Factor (EGFR) Mutant Non-small Cell Lung Cancer (NSCLC) After EGFR Tyrosine Kinase Inhibitor (TKI)

NCT02342353

Description:

The goal of the study is to find the best dose of pacritinib when given in combination with erlotinib.

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

Terminated

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Pacritinib</span> in Patients With Endothelial Growth Factor (<span class="go-doc-concept go-doc-biomarker">EGFR</span>) <span class="go-doc-concept go-doc-keyword">Mutant</span> Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> (NSCLC) After <span class="go-doc-concept go-doc-biomarker">EGFR</span> <span class="go-doc-concept go-doc-intervention">Tyrosine Kinase Inhibitor</span> (<span class="go-doc-concept go-doc-intervention">TKI</span>)

Title

  • Brief Title: Pacritinib in Patients With Endothelial Growth Factor (EGFR) Mutant Non-small Cell Lung Cancer (NSCLC) After EGFR Tyrosine Kinase Inhibitor (TKI)
  • Official Title: A Phase I/II Study of Pacritinib in Patients With EGFR Mutant NSCLC After EGFR TKI
  • Clinical Trial IDs

    NCT ID: NCT02342353

    ORG ID: 201503052

    Trial Conditions

    Nonsmall Cell Lung Cancer

    Non-Small Cell Lung Cancer

    Carcinoma, Non-Small-Cell Lung

    Trial Interventions

    Drug Synonyms Arms
    Pacritinib SB1518 Phase I (pacritinib and erlotinib), Phase II (pacritinib and erlotinib)
    Erlotinib Tarceva, OSI-774 Phase I (pacritinib and erlotinib), Phase II (pacritinib and erlotinib)

    Trial Purpose

    There are two parts to this study: the goal of the first part of the study is to find the
    best dose of pacritinib when given in combination with erlotinib. The goal of the second
    part of the study is to look at the response rate of pacritinib and erlotinib when given in
    combination.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Phase I (pacritinib and erlotinib) Experimental Pacritinib will be administered orally twice a day; dosing will depend on the dose level the patient is enrolled. Erlotinib will be taken by mouth on an outpatient basis daily at a dose of 150 mg. A 28-day interval is defined as a cycle Pacritinib, Erlotinib
    Phase II (pacritinib and erlotinib) Experimental Pacritinib will be administered orally twice a day; the dose used will be the dose determined to be the MTD in phase I. Erlotinib will be taken by mouth on an outpatient basis daily at a dose of 150 mg. A 28-day interval is defined as a cycle Pacritinib, Erlotinib

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed metastatic or unresectable locally advanced
    NSCLC with known sensitive EGFR mutations.

    - Disease progression following therapy with erlotinib, afatinib, or gefitinib

    - May have received one prior treatment with chemotherapy (excluding prior neoadjuvant
    or adjuvant chemotherapy or chemoradiotherapy with curative intent).

    - Measurable disease defined as lesions that can be accurately measured in at least one
    dimension (longest diameter to be recorded) as 10 mm with CT scan, as 20 mm by
    chest x-ray, or 10 mm with calipers by clinical exam.

    - At least 18 years of age.

    - ECOG performance status 1

    - Normal bone marrow and organ function as defined below:

    - Absolute neutrophil count 1,500/mcl

    - Platelets 100,000/mcl

    - Hemoglobin 9.0 g/dL

    - Total bilirubin 2.0 x IULN

    - AST (SGOT) / ALT (SGPT) 3.0 x IULN; if liver metastases, 5.0 x IULN

    - Serum creatinine 1.5 x ULN

    - Women of childbearing potential and men must agree to use adequate contraception
    (hormonal or barrier method of birth control, abstinence) prior to study entry and
    for the duration of study participation. Should a woman become pregnant or suspect
    she is pregnant while participating in this study, she must inform her treating
    physician immediately.

    - Able to swallow pills

    - Able to understand and willing to sign a Human Research Protection Office (HRPO)
    approved written informed consent document (or that of legally authorized
    representative, if applicable).

    Exclusion Criteria:

    - Known pre-existing interstitial lung disease.

    - Leptomeningeal carcinomatosis or other untreated or symptomatic central nervous
    system (CNS) metastases. Patients with asymptomatic CNS metastases, other than
    leptomeningeal disease, are eligible provided they have been clinically stable
    without requiring increase in steroid dose for at least 4 weeks.

    - A history of other malignancy 5 years previous with the exception of basal cell or
    squamous cell carcinoma of the skin which were treated with local resection only or
    carcinoma in situ of the cervix.

    - Currently receiving any other investigational agents.

    - A history of allergic reactions attributed to compounds of similar chemical or
    biologic composition to pacritinib or other agents used in the study.

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, or psychiatric illness/social situations that would limit compliance with
    study requirements.

    - Pregnant and/or breastfeeding: Patient must have a negative pregnancy test within 14
    days of study entry.

    - Known HIV-positivity on combination antiretroviral therapy because of the potential
    for pharmacokinetic interactions with pacritinib. In addition, these patients are at
    increased risk of lethal infections when treated with marrow-suppressive therapy.
    Appropriate studies will be undertaken in patients receiving combination
    antiretroviral therapy when indicated.

    - Use of potent cytochrome P450 3A4 (CYP3A4) inhibitor within one week of pacritinib
    initiation

    - Patients with CTCAE grade 2 cardiac arrhythmias may be considered for inclusion if
    the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety.
    Patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade
    3, corrected QT interval (QTc) prolongation >450ms, or other factors that increase
    the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as
    serum potassium <3.0mEq/L that is persistent and refractory to correction], or family
    history of long QT interval syndrome).

    - Any gastrointestinal (GI) or metabolic condition that could interfere with absorption
    of oral medication such as ongoing grade 3 or higher diarrhea, constipation, nausea,
    or vomiting.

    - Active viral hepatitis.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Dose-limiting toxicities and maximum tolerated dose (MTD) - Phase I only

    Response rate - Phase II only

    Secondary Outcome Measures

    Adverse events (toxicities)

    Disease control rate (DCR)

    Progression-free survival (PFS)

    Overall survival (OS)

    Trial Keywords