Clinical Trials /

Expanded Treatment Protocol With LDK378 in ALK(+) NSCLC

NCT01947608

Description:

Novartis-sponsored, open-label, multi-center, interventional ETP to provide LDK378 to patients with ALK (+)NSCLC, who have been pre-treated with an ALK inhibitor; except in countries where ALK inhibitors are not approved or available. The protocol will further evaluate the safety of LDK378 in patients with ALK(+) NSCLC.

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

Available

Trial Eligibility

Document

Expanded Treatment Protocol With <span class="go-doc-concept go-doc-intervention">LDK378</span> in <span class="go-doc-concept go-doc-biomarker">ALK</span>(+) NSCLC

Title

  • Brief Title: Expanded Treatment Protocol With LDK378 in ALK(+) NSCLC
  • Official Title: An Open-label, Multi-center, Expanded Treatment Protocol (ETP) of Oral LDK378 in Adult Patients With Non-small Cell Lung Cancer (NSCLC) Characterized by ALK Positivity
  • Clinical Trial IDs

    NCT ID: NCT01947608

    ORG ID: CLDK378A2402

    Trial Conditions

    Non-small Cell Lung Cancer (NSCLC)

    Trial Interventions

    Drug Synonyms Arms
    LDK378

    Trial Purpose

    Novartis-sponsored, open-label, multi-center, interventional ETP to provide LDK378 to
    patients with ALK (+)NSCLC, who have been pre-treated with an ALK inhibitor; except in
    countries where ALK inhibitors are not approved or available. The protocol will further
    evaluate the safety of LDK378 in patients with ALK(+) NSCLC.

    Detailed Description

    Trial Arms

    Name Type Description Interventions

    Eligibility Criteria

    Inclusion Criteria (patients eligible for inclusion in this early treatment protocol have
    to meet all of the following criteria):

    1. Histologically or cytologically confirmed diagnosis of NSCLC that demonstrates ALK
    positivity as assessed by approved FISH test (Abbott Molecular Inc), using Vysis
    breakapart probes (defined as 15% or more positive tumor cells); or the Ventana IHC
    test. If documentation of ALK positivity is not available, the test to confirm ALK
    positivity must be performed according to the above criterion, using a new tumor
    biopsy obtained prior to the first dose of ETP treatment (LDK378).

    2. Stage IIIB or IV NSCLC patient with documented disease progression at enrollment, and
    who does not qualify or have access to LDK378 through a clinical trial.

    3. Age 18 years or older at the time of informed consent.

    4. WHO performance status 0-3.

    5. Patients who have been pre-treated with an ALK inhibitor for locally advanced or
    metastatic NSCLC. Patients may be enrolled without prior exposure to an ALK
    inhibitor in countries where ALK inhibitors are not approved or available. Exposure
    to prior chemotherapy is not required.

    6. Patients must have recovered from all toxicities related to prior anticancer
    therapies to grade 2 (CTCAE v 4.03), provided that concomitant medication is given
    prior to initiation of treatment with LDK378. Exception to this criterion: patients
    with any grade of alopecia are allowed to enter the treatment.

    7. The following laboratory criteria have been met:

    - Absolute neutrophil count (ANC) 1.5 x 109/L

    - Hemoglobin (Hgb) 8 g/dL

    - Platelets 75 x 109/L

    - Serum total bilirubin 1.5 x upper limit of normal (ULN), except for patients
    with Gilbert's syndrome who may be included if total bilirubin 3.0 x ULN and
    direct bilirubin 1.5 x ULN

    - Aspartate transaminase (AST) < 3.0 x ULN, except for patients with liver
    metastasis, who are only included if AST < 5 x ULN; alanine transaminase (ALT) <
    3.0 x ULN, except for patients with liver metastasis, who are only included if
    ALT < 5 x ULN.

    - Calculated or measured creatinine clearance (CrCL) 30 mL/min

    8. Patient must have the following laboratory values or have the following laboratory
    values corrected with supplements to be within normal limits at screening:

    - Potassium LLN

    - Magnesium LLN

    - Phosphorus LLN

    - Total calcium (corrected for serum albumin) LLN

    9. Written informed consent for the ETP protocol must be obtained prior to any screening
    procedures. If consent cannot be expressed in writing, it must be formally documented
    and witnessed, ideally via an independent trusted witness.

    10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
    tests and other ETP procedures.

    Exclusion Criteria (patients eligible for this ETP must not meet any of the following
    criteria):

    1. Patients with known hypersensitivity to any of the excipients of LDK378
    (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and
    magnesium stearate).

    2. Patients with symptomatic CNS metastases who are neurologically unstable or have
    required increasing doses of steroids within the 1 week prior to ETP entry to manage
    CNS symptoms.

    3. Prior therapy with LDK378.

    4. The patient is less than 5 half-lives from prior ALK inhibitor or targeted therapy
    (for adequate wash-out) without recovery from treatment toxicities to grade 1 or to
    their pretreatment levels.

    5. Chemotherapy or an investigational therapy 3 weeks prior to starting the LDK378
    treatment who have not recovered from side effects of such treatment toxicities to
    grade 2 or to their pre- treatment toxicities levels, with the exception of liver and
    cardiac functions which must be grade 1.

    6. Patients who have received thoracic radiotherapy to lung fields 4 weeks prior to
    starting the study treatment or patients who have not recovered from
    radiotherapy-related toxicities. For all other anatomic sites (including
    radiotherapy to thoracic vertebrae and ribs) radiotherapy 2 weeks prior to starting
    the LDK378 treatment or have not recovered from radiotherapy-related toxicities.
    Palliative radiotherapy for bone lesions 2 weeks prior to starting LDK378 treatment
    is allowed.

    7. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks
    prior (2 weeks for resection of brain metastases) to starting LDK378 treatment or who
    have not recovered from side effects of such procedures. Video-assisted thoracic
    surgery (VATS) and mediastinoscopy will not be counted as major surgery, and patients
    can be enrolled in the ETP 2 weeks after the procedure.

    8. Presence or history of a malignant disease other than NSCLC that has been diagnosed
    and/or required therapy within the past 3 years. Exceptions to this exclusion include
    the following: completely resected basal cell and squamous cell skin cancers, and
    completely resected carcinoma in situ of any type.

    9. Patients with known history of extensive disseminated bilateral interstitial fibrosis
    or interstitial lung disease, including a history of pneumonitis, hypersensitivity
    pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically
    significant radiation pneumonitis (i.e. affecting activities of daily living or
    requiring therapeutic intervention).

    10. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac
    event (within 6 months), such as:

    - unstable angina within 6 months prior to screening;

    - myocardial infarction within 6 months prior to screening;

    - history of documented congestive heart failure (New York Heart Association
    functional classification III-IV);

    - uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) 160 mm Hg
    and/or Diastolic Blood Pressure (DBP) 100 mm Hg, with or without
    antihypertensive medication -

    - initiation or adjustment of antihypertensive medication(s) is allowed prior to
    screening;

    - ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled
    with medication;

    - other cardiac arrhythmia not controlled with medication;

    - corrected QTc > 450 msec using Fridericia correction on the screening ECG

    11. Impaired GI function or GI disease that may alter absorption of LDK378 or inability
    to swallow up to five LDK378 capsules daily

    12. Ongoing GI adverse events > grade 2 (e.g. nausea, vomiting, or diarrhea) at the start
    of the ETP.

    13. Receiving medications that meet one of the following criteria and that cannot be
    discontinued at least 1 week prior to the start of treatment with LDK378 and for the
    duration of the ETP participation (see Appendix 1: Tables 14-1, Table 14-2, Table
    14-3, and Table 14-4):

    - Medication with a known risk of prolonging the QT interval or inducing Torsades
    de Pointes (please refer to
    http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm)

    - Strong inhibitors or strong inducers of CYP3A4/5 (please refer to
    http://medicine.iupui.edu/flockhart/table.htm or
    http://www.druginteractioninfo.org)

    - Medications with a low therapeutic index that are primarily metabolized by
    CYP3A4/5, CYP2C8 and/or CYP2C9 (please refer to
    http://medicine.iupui.edu/flockhart/table.htm or
    http://www.druginteractioninfo.org)

    - Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived
    anti-coagulant. Anticoagulants not derived from warfarin are allowed (eg,
    dabigatran, rivaroxaban, apixaban).

    - Unstable or increasing doses of corticosteroids

    - enzyme-inducing anticonvulsive agents

    - herbal supplements

    14. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
    female after conception and until the termination of gestation, confirmed by a
    positive hCG laboratory test.

    15. Women of child-bearing potential, defined as all women physiologically capable of
    becoming pregnant, unless they are using highly effective methods of contraception
    during dosing and for 3 months after the last dose of study treatment.

    In case of use of oral contraception, women should have been stable on the same pill
    for a minimum of 3 months before taking study treatment.

    Women are considered post-menopausal and not of child bearing potential if they have
    had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
    profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical
    bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six
    weeks prior to screening. In the case of oophorectomy alone, only when the
    reproductive status of the woman has been confirmed by follow up hormone level
    assessment is she considered not of child bearing potential.

    16. Sexually active males unless they use a condom during intercourse while taking drug
    and for 3 months after the last dose of study treatment. Male patients for 3 months
    should not father a child in this period. A condom is required to be used also by
    vasectomized men in order to prevent delivery of the drug via seminal fluid.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Secondary Outcome Measures

    Trial Keywords