Clinical Trials /

Pemetrexed Disodium and Hsp90 Inhibitor AUY922 in Treating Patients With Previously Treated Stage IV Non-Small Cell Lung Cancer

NCT01784640

Description:

This phase I trial studies the side effects and the best dose of Hsp90 inhibitor AUY922 when given together with pemetrexed disodium in treating patients with previously treated stage IV non-small cell lung cancer. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cell, either by killing the cells or stopping them from dividing. Giving Hsp90 inhibitor AUY922 together with pemetrexed disodium may kill more tumor cells

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

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Pemetrexed Disodium</span> and <span class="go-doc-concept go-doc-intervention">Hsp90 Inhibitor AUY922</span> in Treating Patients With Previously Treated Stage IV Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: Pemetrexed Disodium and Hsp90 Inhibitor AUY922 in Treating Patients With Previously Treated Stage IV Non-Small Cell Lung Cancer
  • Official Title: A Phase IB Dose-Escalation Study of Pemetrexed and AUY922 in Previously-Treated Patients With Metastatic Non-Squamous, Non-Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT01784640

    ORG ID: L-05

    NCI ID: NCI-2013-00410

    Trial Conditions

    Recurrent Non-small Cell Lung Cancer

    Squamous Cell Lung Cancer

    Stage IV Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Hsp90 inhibitor AUY922 AUY922 Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium)
    pemetrexed disodium ALIMTA, LY231514, MTA Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium)

    Trial Purpose

    This phase I trial studies the side effects and the best dose of Hsp90 inhibitor AUY922 when
    given together with pemetrexed disodium in treating patients with previously treated stage
    IV non-small cell lung cancer. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by
    blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as
    pemetrexed disodium, work in different ways to stop the growth of tumor cell, either by
    killing the cells or stopping them from dividing. Giving Hsp90 inhibitor AUY922 together
    with pemetrexed disodium may kill more tumor cells

    Detailed Description

    PRIMARY OBJECTIVES:

    I. Evaluate the safety and tolerability of escalating doses of AUY922 (Hsp90 inhibitor
    AUY922) when given with pemetrexed (pemetrexed disodium) 500 mg/m^2 in participants with
    previously-treated stage IV non-squamous, non-small cell lung cancer (NSCLC).

    SECONDARY OBJECTIVES:

    I. Determine the objective tumor response rate as defined by Response Evaluation Criteria in
    Solid Tumors (RECIST) 1.1 criteria in participants with previously treated non-squamous
    NSCLC treated with pemetrexed and AUY922.

    II. Evaluate the pharmacokinetic profile of pemetrexed and AUY922. III. Evaluate toxicity,
    including visual toxicity, in participants treated with AUY922 and pemetrexed.

    IV. Analyze tumor-tissue biomarkers for potential correlation with response.

    OUTLINE: This is a dose-escalation study of Hsp90 inhibitor AUY922.

    Patients receive Hsp90 inhibitor AUY922 intravenously (IV) over 60 minutes weekly and
    pemetrexed disodium IV over 15 minutes every 3 weeks. Courses repeat every 21 days for 6
    months in the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up at 30 days.

    Trial Arms

    Name Type Description Interventions
    Treatment (Hsp90 inhibitor AUY922, pemetrexed disodium) Experimental Patients receive Hsp90 inhibitor AUY922 IV over 60 minutes weekly and pemetrexed disodium IV over 15 minutes every 3 weeks. Courses repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity. Hsp90 inhibitor AUY922, pemetrexed disodium

    Eligibility Criteria

    Inclusion Criteria:

    - Ability to understand the purpose and risks of the study and provide signed and dated
    informed consent and authorization to use protected health information (PHI) in
    accordance with national and local subject privacy regulations

    - Histologically- or cytologically-confirmed stage IV non-squamous, NSCLC who have
    progressed after at least one prior line of treatment; in the expansion phase,
    participants are only eligible if their molecular category has not been fully
    enrolled (10 participants with epidermal growth factor receptor (EGFR) mutations, 5
    participants with anaplastic lymphoma receptor tyrosine kinase (ALK) gene
    rearrangement, 5 participants with wild type v-Ki-ras2 Kirsten rat sarcoma viral
    oncogene homolog (KRAS), EGFR and ALK)

    - At least one measurable lesion as defined by modified RECIST version 1.1; previously
    irradiated lesions are not measurable unless the lesion is new or has demonstrated
    clear progression after radiation

    - Last chemotherapy or treatment with another systemic anti-cancer agent must have
    stopped >= 4 weeks prior to enrollment (or >= 5 half-lives for oral tyrosine-kinase
    inhibitors or 2 weeks for palliative radiotherapy); participants must have recovered
    (Common Terminology Criteria for Adverse Events [CTCAE] =< 1 or baseline) from acute
    toxicities of any previous therapy (with the exception of alopecia)

    - Eastern Cooperative Oncology Group (ECOG) performance status =< 2

    - Expected survival time of >= 3 months in the opinion of the investigator

    - Absolute neutrophil count (ANC) >=1.5 x 10^9/L

    - Hemoglobin (Hgb) >= 9 g/dl

    - Platelets (plt) >= 100 x 10^9/L

    - Potassium within normal limits

    - Total calcium (corrected for serum albumin) within normal limits or corrected with
    supplements

    - Magnesium within lower limits or corrected with supplements

    - Phosphorus within lower limits or corrected with supplements

    - Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and
    alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 1.5 x
    upper limit of normal (ULN)

    - AST/SGOT and ALT/SGPT =< 2.5 x upper limit of normal (ULN) if liver metastases are
    present

    - Serum bilirubin =< 1.5 x ULN

    - Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 ml/min

    - Negative serum or urine pregnancy test; the serum pregnancy test must be obtained
    prior to the first administration of AUY922 (=< 14 days prior to dosing) in all
    pre-menopausal women and women < 2 years after the onset of menopause

    - Ability to provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample
    containing representative tumor tissue from a previously obtained biopsy/resection
    that meets specific tissue sample requirements at screening

    Exclusion Criteria:

    - Unresolved diarrhea >= CTCAE (v4.0) grade 1

    - Pregnant or lactating women

    - Fertile women of childbearing potential (WCBP) not using (or refusing to use)
    adequate methods of contraception as agreed on between her and the consenting
    investigator; male participants not using (or refusing to use) a condom during
    intercourse

    - History of another primary cancer within 3 years prior to enrollment with the
    exception of curatively treated skin cancer (other than melanoma) or curatively
    treated cervical carcinoma in-situ

    - History of central nervous system (CNS) metastasis; Note: participants without
    clinical signs and symptoms of CNS involvement are not required to have magnetic
    resonance imaging (MRI) of the brain; (exception: participants with treated brain
    metastases who are asymptomatic, not currently on steroid therapy, and clinically
    stable for >= 2 weeks will be eligible for protocol participation)

    - Prior treatment with pemetrexed

    - Prior anti-neoplastic treatment with any heat shock protein 90 (HSP90) or histone
    deacetylase (HDAC) inhibitor compound

    - Participants who have undergone any major surgery =< 2 weeks prior to starting study
    drug or who have not recovered from side effects of such therapy

    - Last chemotherapy or treatment with another systemic anti-cancer agent must have
    stopped >= 4 weeks prior to enrollment (or >= 5 half-lives for oral tyrosine-kinase
    inhibitors); participants with EGFR mutations and ALK gene rearrangement who have not
    received a tyrosine kinase inhibitor targeting their molecular abnormality (e.g.,
    erlotinib or crizotinib respectively); participants must have recovered (CTCAE =< 1)
    from acute toxicities of any previous therapy (with the exception of alopecia)

    - Participants who have concurrent or uncontrolled illness that the investigator feels
    will impede study participation including, but not limited to:

    - Acute or chronic liver disease

    - Acute or chronic renal disease

    - Active or ongoing infection

    - Psychiatric illness/social situations that would limit compliance with study
    requirements

    - Participants with known disorders due to a deficiency in bilirubin glucuronidation
    (e.g. Gilbert's syndrome)

    - Intolerance of Vitamin B12, folic acid or dexamethasone

    - Participants with following cardiac criteria:

    - History of long QT syndrome

    - QTcF >= 450 ms during screening electrocardiogram (ECG)

    - History of clinically manifest ischemic heart disease including myocardial
    infarction, stable or unstable angina pectoris, coronary arteriography or
    cardiac stress testing/imaging with findings consistent with infarction or
    clinically significant coronary occlusion 6 months prior to study start

    - History of heart failure or left ventricular (LV) dysfunction (LV ejection
    fraction [EF] =< 45%) by multi gated acquisition scan (MUGA) or echocardiogram
    (ECHO)

    - Clinically significant ECG abnormalities including one or more of the following:
    left bundle branch block (LBBB), right bundle branch block (RBBB) with left
    anterior hemiblock (LAHB); ST segment elevations or depressions > 1mm, or 2nd
    (Mobitz II) or 3rd degree atrioventricular block (AV) block

    - History and presence of atrial fibrillation, atrial flutter or ventricular
    arrhythmias including ventricular tachycardia or Torsades de pointes

    - Other clinically significant heart disease (e.g. congestive heart failure,
    uncontrolled hypertension, history of labile hypertension, or history of poor
    compliance with a hypertensive regimen)

    - Clinically significant resting bradycardia (< 50 beats per minute)

    - Participants who are currently receiving treatment with any medication which has
    a relative risk or prolonging the QTcF interval or inducing Torsades de pointes
    (as listed in protocol) and cannot be switched or discontinued to an alternative
    drug prior to commencing AUY922 dosing

    - Participants who are on a cardiac pacemaker

    - Participants unwilling or unable to comply with the protocol

    - Participants known to be human immunodeficiency virus (HIV) positive; testing is not
    required in the absence of clinical signs and symptoms suggesting HIV infection

    - Any systemic anti-cancer treatment out of allowed timelines

    - Concurrent cytotoxic or immunosuppressive therapy for non-malignant disease (e.g.,
    for rheumatoid arthritis or lupus)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of adverse events (AEs) as assessed by National Cancer Institute (NCI) CTCAE version 4.0

    Secondary Outcome Measures

    Tumor response rate according to RECIST version 1.1

    Trial Keywords