Clinical Trials /

Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors

NCT02478320

Description:

The goal of this clinical research study is to learn if ilorasertib (ABT-348) can help to control CDKN2A-deficient cancer. CDKN2A deficiency is a type of mutation (a genetic change). The safety of this drug will also be studied.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Phase II Study of <span class="go-doc-concept go-doc-intervention">Ilorasertib</span> (ABT348) in Patients With <span class="go-doc-concept go-doc-biomarker">CDKN2A</span> <span class="go-doc-concept go-doc-keyword">Deficient</span> Solid Tumors

Title

  • Brief Title: Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors
  • Official Title: A Proof-of-Concept Study for Ilorasertib (ABT-348) Activity in Patients With CDKN2A-Deficient Advanced Solid Cancers: a Phase II Basket Trial
  • Clinical Trial IDs

    NCT ID: NCT02478320

    ORG ID: 2014-0920

    NCI ID: NCI-2015-01251

    Trial Conditions

    Advanced Cancers

    Trial Interventions

    Drug Synonyms Arms
    Ilorasertib ABT-348 Ilorasertib (ABT-348)

    Trial Purpose

    The goal of this clinical research study is to learn if ilorasertib (ABT-348) can help to
    control CDKN2A-deficient cancer. The safety of this drug will also be studied.

    Detailed Description

    Study Drug Administration:

    Each study cycle is 28 days. You will take ABT-348 by mouth 2 times each day on Days 1, 8,
    and 15 of each cycle. The first dose you take on these days is called Dose 1, and the second
    dose you take each day is called Dose 2.

    You will take Dose 1 (the earlier dose) of ABT-348 with 4 ounces (about cup) of water. You
    should fast (not eat or drink anything except water) for 8 hours before taking this dose.
    You need to fast before this dose because eating food may affect the levels of the study
    drug that is able to enter your system. You will be allowed to have a light snack 2 hours
    after Dose 1, and then you may eat anything you like 4 hours after the dose.

    You should take Dose 2 (the later dose) as close as possible to 6 hours after the first
    dose, but not less than 6 hours after the first dose. You do not need to fast before Dose 2.
    You may eat and drink normally around this dose.

    Study Visits:

    On Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2:

    - You will have a physical exam.

    - Blood (about 2 teaspoons) will be drawn for routine tests.

    - You will have an EKG (Days 1 and 15 only). After Cycle 3, you will have these EKGs
    repeated every 3 cycles (Cycles 6, 9, 12, and so on).

    On Day 1 of all cycles, urine will be collected for routine tests.

    Every 8 weeks, you will have a chest x-ray, bone scan, MRI/CT or PET/CT to check the status
    of the disease.

    You may be able to have some of these tests/procedures performed at a local lab, clinic, or
    doctor's office that is closer to your home. The results of these tests will be sent to the
    study doctor for review. The study doctor or research staff will discuss this option with
    you in more detail.

    Length of Study Drug Administration:

    You may continue taking the study drug for as long as the doctor thinks it is in your best
    interest. You will no longer be able to take the study drug if the disease gets worse, if
    intolerable side effects occur, or if you are unable to follow study directions.

    You participation on this study will be over after your last dose of study drug.

    This is an investigational study. ABT-348 is not FDA approved or commercially available. It
    is currently being used for research purposes only. The study doctor can explain how the
    study drug is designed to work.

    Up to 65 participants will be enrolled in this study. All will take part at MD Anderson.

    Trial Arms

    Name Type Description Interventions
    Ilorasertib (ABT-348) Experimental Ilorasertib 200 mg administered by mouth twice daily on Days 1, 8, and 15 of each 28-day cycle. Ilorasertib

    Eligibility Criteria

    Inclusion Criteria:

    1. Patients with histologically confirmed, advanced or metastatic cancer for which
    standard curative or palliative measures do not exist or are no longer effective.

    2. Patients must have CDKN2A-deficient tumor (deletion or mutation). Definition of
    CDKN2A deficient tumor: #1. CDKN2A deletion or mutation by any CLIA-certified
    sequencing #2. >/= 30% of tumor cells with (at least) hemizygous deletion by FISH.
    Status will be determined from archived tissue.

    3. Patients must have measurable disease by RECIST 1.1.

    4. Patients must be >/=18 years of age.

    5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.

    6. Subject has adequate renal function as demonstrated by serum creatinine value of </=
    1.5 times the upper limit of normal (ULN) and either an estimated creatinine
    clearance value of >/= 50 mL/min as determined by the Cockcroft-Gault formula or a
    creatinine clearance value of >/= 50 mL/min based on a 24 hour urine collection.

    7. Subject has adequate liver function as demonstrated by serum bilirubin </= 2 x ULN
    and AST and ALT </= 2.5 x ULN. For subjects with liver metastasis, adequate liver
    function is demonstrated by serum bilirubin </= 2 x ULN and AST/ALT </= 5.0 x ULN.

    8. Subject has adequate bone marrow as demonstrated by absolute neutrophil count (ANC)
    >/= 1,500/mm3 (1.5 x 10^9/L); Platelets >/= 100,000/mm2 (100 x 10^9/L); Hemoglobin
    >/= 9.0 g/dL (1.4 mmol/L).

    9. Subject has QTc interval < 500 msec on baseline electrocardiogram.

    10. The subject has a documented Left Ventricular Ejection Fraction > 50%.

    11. Women of child-bearing potential and men must agree to use adequate contraception
    (one of the following listed below) prior to the study entry, for the duration of
    study participation and up to 3 months following completion of therapy. Women of
    child-bearing potential must have a negative pregnancy test within 7 days prior to
    initiation of treatment and/or post menopausal women must be amenorrheic for at least
    12 months to be considered of non-childbearing potential. -Total abstinence from
    sexual intercourse (minimum one complete menstrual cycle) -Vasectomized male subjects
    or vasectomized partner of female subjects -Intrauterine device -Double-barrier
    method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal
    jellies or cream) -Additionally, male subjects (including those who are vasectomized)
    whose partners are pregnant or might be pregnant must agree to use condoms for the
    duration of the study and for 3 months following completion of therapy.

    12. Ability to understand and willingness to sign informed consent form prior to
    initiation of the study and any study procedures.

    13. Signed informed consent approved by the Institutional Review Board prior to patient
    entry

    Exclusion Criteria:

    1. Patients with CDKN2A wild type by a CLIA-certified laboratory

    2. Subject has known active CNS involvement. The subject has untreated brain or
    meningeal metastases. CT scans are not required to rule out brain or meningeal
    metastases unless there is a clinical suspicion of central nervous system disease.
    Subjects with treated brain metastases that are radiographically or clinically stable
    for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage
    in the brain lesion(s) are eligible, providing that they are asymptomatic, and do not
    require corticosteroids (must have discontinued steroids at least 1 week prior to
    study drug administration).

    3. Subject has received anti-cancer therapy including chemotherapy, immunotherapy,
    radiotherapy, hormonal, biologic or any investigational therapy within a period of 21
    days or 5 half-lives (whichever is shorter) prior to Study Day 1.

    4. Subject has unresolved toxicities from prior anti-cancer therapy, defined as any
    Common Terminology Criteria for Adverse Events (NCI CTCAE v 4.0) grade 2 or higher
    clinically significant toxicity (excluding alopecia).

    5. Subject has had major surgery within 28 days prior to Study Day 1.

    6. Subject currently exhibits symptomatic or persistent, uncontrolled hypertension
    defined as diastolic blood pressure > 90 mmHg or systolic blood pressure > 140 mmHg.
    Subjects may be re-screened if blood pressure is shown to be controlled with or
    without intervention.

    7. Subject has proteinuria defined by the National Cancer Institute Common Terminology
    Criteria for Adverse Events (NCI CTCAE v 4.0) grade > 1 at baseline as measured by a
    urine dipstick (2+ or greater) and confirmed by a 24 hour urine collection (>/= 1
    g/24 hrs). Subjects may be re-screened if proteinuria is shown to be controlled with
    or without intervention.

    8. Subject is receiving therapeutic anticoagulation therapy. Low dose anti-coagulation
    (e.g., low dose heparin or warfarin) for catheter prophylaxis will be permitted. Use
    of Aspirin for treatment of Atrial Fibrillation will also be permitted.

    9. Patients with another primary malignancy within 3 years prior to starting study
    treatment with the exception of adequately treated basal cell carcinoma, squamous
    cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the
    uterine cervix.

    10. Clinically significant uncontrolled condition(s) including but not limited to: Active
    uncontrolled infection, Symptomatic congestive heart failure, Unstable angina
    pectoris or cardiac arrhythmia (subjects with stable atrial fibrillation are not
    excluded), History of adrenal insufficiency.

    11. Psychiatric illness/social situation that would limit compliance with study
    requirements.

    12. Subject has a known infection with HIV, Hepatitis B or Hepatitis C.

    13. Subject has poorly controlled diabetes mellitus defined as HbA1c > 7%; subjects with
    a history of transient glucose intolerance due to corticosteroid administration are
    allowed in this study if all other inclusion/exclusion criteria are met.

    14. Any medical condition which in the opinion of the study investigator places the
    subject at an unacceptably high risk for toxicities.

    15. Subject is unable to swallow or absorb oral tablets normally

    16. Female subject who is lactating or pregnant.

    17. Subject takes CYP3A Inhibitors/Inducers within 7 days prior to the study drug
    administration.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Response Rate of Ilorasertib (ABT-348) in Participants with Cancers Harboring CDKN2A Deletion or Mutation as Tumor Response

    Secondary Outcome Measures

    Trial Keywords

    Advanced Cancers

    CDKN2A-Deficient Advanced Solid Cancers

    Advanced or metastatic cancer.

    Ilorasertib

    ABT-348