Clinical Trials /

Trial of Ruxolitinib and Erlotinib in Patients With EGFR-mutant Lung Adenocarcinoma With Acquired Resistance to Erlotinib

NCT02155465

Description:

This is a phase 2 study. The goal of this study is to find out what effects, good and/or bad, taking erlotinib and ruxolitinib has on the patients and on lung cancer. Erlotinib and ruxolitinib are FDA approved for other indications, but the use of erlotinib and ruxolitinib together has not been studied before and is not FDA-approved.

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

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Trial of <span class="go-doc-concept go-doc-intervention">Ruxolitinib</span> and <span class="go-doc-concept go-doc-intervention">Erlotinib</span> in Patients With <span class="go-doc-concept go-doc-biomarker">EGFR</span>-<span class="go-doc-concept go-doc-keyword">mutant</span> Lung Adenocarcinoma With Acquired Resistance to <span class="go-doc-concept go-doc-intervention">Erlotinib</span>

Title

  • Brief Title: Trial of Ruxolitinib and Erlotinib in Patients With EGFR-mutant Lung Adenocarcinoma With Acquired Resistance to Erlotinib
  • Official Title: A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients With EGFR-mutant Lung Adenocarcinoma With Acquired Resistance to Erlotinib
  • Clinical Trial IDs

    NCT ID: NCT02155465

    ORG ID: 14-043

    Trial Conditions

    Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Ruxolitinib Ruxolitinib and Erlotinib
    Erlotinib Ruxolitinib and Erlotinib

    Trial Purpose

    This is a phase 2 study. The goal of this study is to find out what effects, good and/or
    bad, taking erlotinib and ruxolitinib has on the patients and on lung cancer. Erlotinib and
    ruxolitinib are FDA approved for other indications, but the use of erlotinib and ruxolitinib
    together has not been studied before and is not FDA-approved.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Ruxolitinib and Erlotinib Experimental Phase I The study will follow a standard 3+3 dose escalation trial design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (21 days) before a dose escalation decision is made. Phase II Once the MTD has been determined, patients will be enrolled in the phase 2 portion of the single-arm, two-stage, open-label study to determine efficacy of erlotinib and ruxolitinib. Patients will receive erlotinib and ruxolitinib at the MTD established in the phase I portion. The patient take their previous dose of erlotinib if it is less than 150mg daily. Ruxolitinib, Erlotinib

    Eligibility Criteria

    Inclusion Criteria:

    - Pathologic evidence of advanced (non-operable or metastatic) biopsy-proven stage IV
    or recurrent lung cancer reviewed at MSKCC.

    - a documented somatic activating mutation in EGFR (including but not limited to Exon
    19 deletion or L858R)

    - Radiographic progression during treatment with erlotinib. Prior chemotherapy regimens
    are permitted.

    - Received erlotinib or other EGFR TK treatment for at least 2 weeks prior to
    enrollment

    - Measurable (RECIST 1.1) indicator lesion not previously irradiated

    - Must have undergone biopsy after development of acquired resistance to erlotinib
    (which is performed as standard of care) with adequate tissue to determine EGFR T790M
    and tumor histology. Slides from an outside institution may be used.

    - KPS 70%

    - Age>18 years old

    - Patients must have adequate organ function:

    - AST, ALT, Alk phos 3.0 x ULN

    - Total bilirubin 2.0 x ULN

    - Creatinine <2.0 X upper limit of normal and/or a creatinine clearance 60ml/min

    - Absolute neutrophil count (ANC) 1,000 cells/mm.

    - Platelet count 100,000/mm

    - Hemoglobin 9.0g/dL.

    Exclusion Criteria:

    - Concurrent therapy with a potent CYP3A4 inducer or inhibitor. Subjects may enter
    screening when therapy with the potent inhibitor or inducer is completed and may
    begin study treatment after 1 week or 5 half-lives, whichever is longer.

    - Patients with symptomatic brain metastasis requiring escalating doses of steroids.

    - Any type of systemic therapy (chemotherapy or experimental drugs) within 3 weeks of
    starting treatment on protocol except for erlotinib or other EGFR TKI.

    - Any radiation within 2 weeks prior to starting treatment on protocol

    - Patients with grade 2 or greater diarrhea despite maximal medical management due to
    medications or a medical condition such as Crohn's disease, malabsorption.

    - Inadequate recovery from any toxicities related to prior treatment (to Grade 1 or
    baseline).

    - Pregnant or lactating women

    - Patients who have received prior treatment with JAK inhibitor

    - Previously or current malignancies at other sites within the last 2 years, with the
    exception of adequately treated in situ carcinoma of the cervix, basal or squamous
    cell carcinoma of the skin, prostate cancer that does not require active treatment
    per National Comprehensive Cancer Network (NCCN) guidelines, superficial bladder
    cancer or other noninvasive indolent or stage 1 malignancy without sponsor approval.

    - Clinically significant cardiac disease including unstable angina, acute myocardial
    infarction within 6 months from Day 1 of study drug administration, New York Heart
    Association Class III or IV congestive heart failure, or symptomatic arrythmias
    requiring therapy,

    - Chronic or current active infections requiring systemic antibiotics, antifungals or
    antiviral therapy.

    - Known human immunodeficiency virus infection, or hepatitis B virus (HBV) viremia or
    hepatitis C virus (HCV) viremia. Screening for the study does not require assessment
    for these infections if not already known.

    - Any other condition that, in the opinion of the Investigator, may compromise the
    safety, compliance of the patient, or would preclude the patient from successful
    completion of the study.

    Minimum Eligible Age: 19 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    maximally tolerated dose (MTD) (Phase I)

    Assess overall response rate (Phase I)

    Secondary Outcome Measures

    toxicity profile (Phase I)

    survival (Phase II)

    Trial Keywords

    Ruxolitinib

    Erlotinib

    EGFR-mutant

    14-043