Clinical Trials /

AUY922 for Advanced ALK-positive NSCLC

NCT01752400

Description:

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause and if the drug is effective for treating your type of cancer. It also means that the FDA has not yet approved the drug for your type of cancer or for any use outside of research studies. It has been found that some people with NSCLC have a change (mutation) in a certain gene called the ALK gene. This mutated gene helps cancer cells grow. There is a drug (crizotinib) that has been approved by the FDA for the treatment of people with NSCLC who have mutations in the ALK gene. Most people respond to crizotinib initially. Over time, however, patients may stop responding (become resistant) to crizotinib because of additional changes in the ALK gene that makes crizotinib ineffective. AUY922 is an investigational drug that may stop cancer cells from growing abnormally. This drug has been used in other research studies. Information from those other research studies suggests that AUY922 may be effective in killing cancer cells that have become resistant to drugs like crizotinib. Only participants with changes in the ALK gene will be allowed to participate in this study. The purpose of this study is to test the safety of AUY922 and determine how well AUY922 treats participants with advanced, ALK-positive NSCLC.

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

Completed

Phase:

Phase 2

Trial Eligibility

Document

AUY922 for Advanced <span class="go-doc-concept go-doc-biomarker">ALK</span>-positive NSCLC

Title

  • Brief Title: AUY922 for Advanced ALK-positive NSCLC
  • Official Title: A Phase II Open-Label Trial of AUY922, an HSP90 Inhibitor, in Patients With ALK-Rearranged Advanced Non-Small Cell Lung Cancer and Acquired Resistance to Prior ALK Tyrosine Kinase Inhibition
  • Clinical Trial IDs

    NCT ID: NCT01752400

    ORG ID: 12-458

    Trial Conditions

    Non Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    AUY922 AUY922

    Trial Purpose

    This research study is a Phase II clinical trial, which tests the safety and effectiveness
    of an investigational drug to learn whether the drug works in treating a specific cancer.
    "Investigational" means that the drug is being studied and that research doctors are trying
    to find out more about it-such as the safest dose to use, the side effects it may cause and
    if the drug is effective for treating your type of cancer. It also means that the FDA has
    not yet approved the drug for your type of cancer or for any use outside of research
    studies.

    It has been found that some people with NSCLC have a change (mutation) in a certain gene
    called the ALK gene. This mutated gene helps cancer cells grow. There is a drug (crizotinib)
    that has been approved by the FDA for the treatment of people with NSCLC who have mutations
    in the ALK gene. Most people respond to crizotinib initially. Over time, however, patients
    may stop responding (become resistant) to crizotinib because of additional changes in the
    ALK gene that makes crizotinib ineffective.

    AUY922 is an investigational drug that may stop cancer cells from growing abnormally. This
    drug has been used in other research studies. Information from those other research studies
    suggests that AUY922 may be effective in killing cancer cells that have become resistant to
    drugs like crizotinib. Only participants with changes in the ALK gene will be allowed to
    participate in this study.

    The purpose of this study is to test the safety of AUY922 and determine how well AUY922
    treats participants with advanced, ALK-positive NSCLC.

    Detailed Description

    If you agree to participate in this research study, you will be asked to undergo some
    screening tests or procedures to find out if you can be in the research study. Many of these
    tests and procedures are likely to be part of regular cancer care and may be done even if it
    turns out that you do not take part in the research study. If you have had some of these
    tests or procedures recently, they may or may not have to be repeated. These test include a
    medical history, physical exam, performance status, assessment of tumor, EKG, echocardiogram
    or multigated acquisition scan, eye exam, blood draw, blood pregnancy test, urine tset and
    collection of a piece of stored tumor tissue. If these tests show you are eligible to
    participate in the research study, you will begin the study treatment. If you do not meet
    the eligibility criteria, you will not be able to participate in this research study.

    Study treatment is given in 21 day cycles. AUY922 is given by IV (into a vein). This is
    called an infusion. You will receive an infusion of AUY922 jon days 1,8 and 15 of each cycle
    (once per week). The infusion will take about 60 minutes.

    A schedule of clinic visits for the study is summarized below. At every visit, you should
    tell the study staff how you are feeling and whether your health has changed. you may have
    other lab tests done as part of the the care of your cancer in addition to those listed
    below.

    Cycle 1, Day 1: physical examination, performance status, EKG, Blood draw and routine urine
    tests.

    Cycle 1, Day 2: EKG

    Cycle 1, Day 3: EKG

    Cycle 1, Day 8: measurement of weight and vital signs, performance status, EKG, questions
    about side effects you may have and medications you are taking

    Cycle 1, Day 15: physical exam, performance status, EKG, blood draw, questions about side
    effects you may have and medications you are taking.

    Note that in Cycle 1 you will need to stay at (or return to) the clinic for the last EKG
    following the Day 1 AUY922 infusion, and come to the clinic on Days 2 and 3 for EKGs

    Cycle 2 and beyond, Day 1: physical exam, performance status, EKG, blood draw, questions
    about side effects you may have and medications you are taking, routine urine test

    Cycle 2 and beyond, Day 8: measurement of weight and vital signs, performance status, EKG,
    questions about side effects and medications

    Cycle 2 and beyond, Day 15: physical exam, vital signs, performance status, EKG, blood draw,
    questions about side effects and medications

    Additional EKGs may be done at any time if your study doctor thinks it is necessary. A blood
    test to measure the amount of cardiac enzymes in your blood may be done whenever abnormal
    findings such as heart rhythm changes are suspected or seen on the EKG. CT or MRI scans will
    be done to measure your disease about every 6 weeks. A blood pregnancy test, for women who
    can become pregnant, will be performed every 6 weeks or at any point in which pregnancy is
    suspected. A standard eye exam will be done on Cycle 3, Day 1. Additional eye exams will be
    done if you experience any eye-related symptoms, such as changes in vision.

    Within 1 week after your last dose of the study drug AUY922, you will be asked to return to
    the clinic for an End of Treatment Visit. At this visit the following will be done: physical
    examination, performance status, ECG, ECHO or MUGA scan, blood draw, urine test, eye exam,
    questions about side effects you may have and medications you are taking.

    You will be asked to return to the clinic about 3 weeks after the End of Treatment Visit
    (about 4 weeks after the last dose of AUY922) so we can follow-up on any side effects you
    may still be experiencing after stopping AUY922.

    If you decide to stop study treatment for a reason other than progression of your disease,
    you will be asked to have follow-up CT scans or MRIs every 12 weeks to continue to monitor
    the status of your cancer. If your tumors get worse, you will not need to have any further
    CT scans (or MRIs) as part of the study.

    If your disease does progress, we would like to contact you by telephone about every 3
    months to check on your status. This will be done until after the last participant stops
    study treatment, or for as long as you allow us to contact you. Keeping in touch with you
    and checking on your condition helps us look at the long term effects of the research.

    You can continue to receive AUY922 for as long as your cancer does not progress and you do
    not experience unacceptable side effects.

    Trial Arms

    Name Type Description Interventions
    AUY922 Experimental Via intravenous infusion on Days 1, 8 and 15 of each 21 day cycle (once per week). Infusion lasts approximately 60 minutes AUY922

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed advanced NSCLC

    - Tumor characterized by abnormalities in ALK

    - Required to provide archival tissue in the form of 5 formalin fixed paraffin embedded
    sections

    - Have acquired resistance to treatment with an ALK-TKI

    - At least one measurable lesion as defined by RECIST criteria

    - Life expectancy of at least 12 weeks

    Exclusion Criteria:

    - Pregnant or breastfeeding

    - Discontinued ALK TKI more than four weeks prior to enrollment

    - Unresolved diarrhea greater than or equal to CTCAE grade 1

    - Not willing to use double barrier methods of contraception

    - Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound

    - Have received cytoxic chemotherapy in the intervening period since discontinuation of
    an ALK-TKI

    - Have undergone major surgery within 2 weeks prior to starting study drug

    - Any concurrent or uncontrolled illness

    - Any known disorders due to a deficiency in bilirubin glucuronidation

    - Taking therapeutic doses of warfarin

    - Any serious cardiac disorders or abnormalities

    - Concurrent malignancies or invasive cancers diagnosed within the past 2 years except
    for adequately treated basal cell cancer of the skin or in situ cancers

    - Known to be HIV positive

    - Known hypersensitivity to any of the study drugs or their excipients

    - Participation in another clinical study within 30 days before the first study
    treatment

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective Response Rate

    Secondary Outcome Measures

    Progression-free survival

    Disease control rate

    Number of patients who develop adverse events on AUY922

    Number of patients with concurrent KRAS mutations

    ALK translocation variant type

    ALK mutation status

    Overall survival

    Trial Keywords

    Advanced