Clinical Trials /

Pembrolizumab and Imatinib in Patients With Locally Advanced/Metastatic Melanoma With c-KIT Mutation/Amplification

NCT02812693

Description:

This phase I/II trial studies the side effects and how well pembrolizumab and imatinib mesylate work in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and imatinib mesylate may work better in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body.

Related Conditions:
  • Melanoma
Recruiting Status:

Withdrawn

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Pembrolizumab</span> and <span class="go-doc-concept go-doc-intervention">Imatinib</span> in Patients With Locally Advanced/Metastatic <span class="go-doc-concept go-doc-disease">Melanoma</span> With c-<span class="go-doc-concept go-doc-biomarker">KIT</span> <span class="go-doc-concept go-doc-keyword">Mutation</span>/<span class="go-doc-concept go-doc-keyword">Amplification</span>

Title

  • Brief Title: Pembrolizumab and Imatinib in Patients With Locally Advanced/Metastatic Melanoma With c-KIT Mutation/Amplification
  • Official Title: A Phase 1/2 Trial of Pembrolizumab in Combination With Imatinib in Patients With Locally Advanced or Metastatic Melanoma With c-KIT Mutation or Amplification
  • Clinical Trial IDs

    NCT ID: NCT02812693

    ORG ID: OSU-15280

    NCI ID: NCI-2016-00864

    Trial Conditions

    Stage IIIA Skin Melanoma

    Stage IIIB Skin Melanoma

    Stage IIIC Skin Melanoma

    Stage IV Skin Melanoma

    Trial Interventions

    Drug Synonyms Arms
    Imatinib Mesylate CGP 57148, CGP57148B, Gleevec, Glivec, STI 571, STI-571, STI571 Treatment (pembrolizumab, imatinib)

    Trial Purpose

    This phase I/II trial studies the side effects and how well pembrolizumab and imatinib
    mesylate work in treating patients with melanoma with c-KIT mutation or amplification that
    has spread to nearby tissue or other places in the body. Monoclonal antibodies, such as
    pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Imatinib
    mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell
    growth. Giving pembrolizumab and imatinib mesylate may work better in treating patients with
    melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other
    places in the body.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To assess the best overall response rate (BORR = complete response + partial response) of
    the combination of pembrolizumab and imatinib for treatment of melanomas harboring c-Kit
    mutation or amplification.

    II. To evaluate the safety and adverse effect profile of the combination of pembrolizumab
    and imatinib in patients with melanomas harboring c-KIT aberrations (mutations or
    amplifications).

    SECONDARY OBJECTIVES:

    I. To assess the median time to progression (TTP), progression free survival (PFS), and
    overall survival (OS).

    TERTIARY OBJECTIVES:

    I. Assessment of programmed cell death ligand (PD-L)1 expression in melanoma patients with
    c-KIT aberrations before and after combined therapy.

    OUTLINE:

    Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and imatinib
    mesylate orally (PO) once daily (QD) on days 1-21. Courses repeat every 3 weeks in the
    absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up at 30 days and every 9 weeks
    for 1 year, and then every 12 weeks thereafter.

    Trial Arms

    Name Type Description Interventions
    Treatment (pembrolizumab, imatinib) Experimental Patients receive pembrolizumab IV over 30 minutes on day 1 and imatinib mesylate orally PO QD on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Imatinib Mesylate

    Eligibility Criteria

    Inclusion Criteria:

    - Patient must have histologically or cytologically confirmed diagnosis of stage III
    melanoma inoperable/not amenable to local treatment or stage IV melanoma.

    - Patient must have either mutation or amplification of c-KIT gene tested by
    commercially available molecular or gene sequencing techniques

    - Be willing and able to provide written informed consent/assent for the trial

    - Have measurable disease based on Response Evaluation Criteria in Solid Tumors
    (RECIST) 1.1

    - Be willing to provide tissue from a newly obtained core or excisional biopsy of a
    tumor lesion; newly-obtained is defined as a specimen obtained up to 6 weeks (42
    days) prior to initiation of treatment on day 1; subjects for whom newly-obtained
    samples cannot be provided (e.g. inaccessible or subject safety concern) may submit
    an archived specimen only upon agreement from the sponsor

    - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
    performance scale

    - Absolute neutrophil count (ANC) >= 1,500 /mcL

    - Platelets >= 100,000 / mcL

    - Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)
    dependency (within 7 days of assessment)

    - Serum creatinine =< 1.5 X upper limit of normal (ULN) or measured or calculated
    creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
    creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine
    levels > 1.5 X institutional ULN

    - Serum total bilirubin =< 1.5 X ULN or direct bilirubin =< ULN for subjects with total
    bilirubin levels > 1.5 ULN

    - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
    alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5
    X ULN OR =< 5 X ULN for subjects with liver metastases

    - Albumin >= 2.5 mg/dL

    - International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
    subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
    time (PTT) is within therapeutic range of intended use of anticoagulants

    - Activated Partial Thromboplastin Time (aPTT) =< 1.5 X ULN unless subject is receiving
    anticoagulant therapy as long as PT or PTT is within therapeutic range of intended
    use of anticoagulants

    - Female subject of childbearing potential must have a negative urine or serum
    pregnancy within 72 hours prior to receiving the first dose of study medication; if
    the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
    will be required

    - Female subjects of childbearing potential must be willing to use 2 methods of birth
    control or be surgically sterile, or abstain from heterosexual activity for the
    course of the study through 120 days after the last dose of study medication;
    subjects of childbearing potential are those who have not been surgically sterilized
    or have not been free from menses for > 1 year

    - Male subjects must agree to use an adequate method of contraception starting with the
    first dose of study therapy through 120 days after the last dose of study therapy

    Exclusion Criteria:

    - Is currently participating and receiving study therapy or has participated in a study
    of an investigational agent and received study therapy or used an investigational
    device within 4 weeks of the first dose of treatment

    - Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within
    7 days prior to the first dose of trial treatment; individuals who are receiving
    systemic steroid therapy at a stable dose less than or equal to 10mg of prednisone
    per day or its equivalent will be permitted to participate

    - Has a known history of active TB (bacillus tuberculosis)

    - Hypersensitivity to pembrolizumab, imatinib, or any of its excipients

    - Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
    day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events
    due to agents administered more than 4 weeks earlier

    - Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
    within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at
    baseline) from adverse events due to a previously administered agent

    - Note: subjects with =< grade 2 neuropathy and/or alopecia are an exception to
    this criterion and may qualify for the study

    - Note: if subject received major surgery, they must have recovered adequately
    from the toxicity and/or complications from the intervention prior to starting
    therapy

    - Has a known additional malignancy that is progressing or requires active treatment;
    exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
    skin that has undergone potentially curative therapy or in situ cervical cancer

    - Has known active central nervous system (CNS) metastases and/or carcinomatous
    meningitis; subjects with previously treated brain metastases may participate
    provided they are stable (without evidence of progression by imaging for at least
    four weeks prior to the first dose of trial treatment and any neurologic symptoms
    have returned to baseline), have no evidence of new or enlarging brain metastases,
    and are not using steroids at a dose exceeding 10mg of prednisone per day or its
    equivalent for at least 7 days prior to trial treatment; this exception does not
    include carcinomatous meningitis, which is excluded regardless of clinical stability

    - Has active autoimmune disease that has required systemic treatment in the past 2
    years (i.e. with use of disease modifying agents, corticosteroids exceeding 10 mg
    prednisone per day or its equivalent, or immunosuppressive drugs); replacement
    therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy
    for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
    treatment

    - Has known history of, or any evidence of, active, non-infectious pneumonitis

    - Has an active infection requiring systemic therapy

    - Has a history or current evidence of any condition, therapy, or laboratory
    abnormality that might confound the results of the trial, interfere with the
    subject's participation for the full duration of the trial, or is not in the best
    interest of the subject to participate, in the opinion of the treating investigator

    - Has decompensated congestive heart failure as defined by New York Heart Association
    (NYHA) functional classification III or IV

    - Has known psychiatric or substance abuse disorders that would interfere with
    cooperation with the requirements of the trial

    - Is pregnant or breastfeeding, or expecting to conceive or father children within the
    projected duration of the trial, starting with the pre-screening or screening visit
    through 120 days after the last dose of trial treatment

    - Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or
    anti-PD-L2 agent

    - Has received prior therapy with imatinib or another tyrosine kinase inhibitor

    - Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

    - Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
    hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
    detected)

    - Has received a live vaccine within 30 days of planned start of study therapy

    - Note: seasonal influenza vaccines for injection are generally inactivated flu
    vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)
    are live attenuated vaccines, and are not allowed

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    BORR

    Secondary Outcome Measures

    Change in PD-1 and PDL-1 expression levels

    Incidence of adverse events assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    OS

    PFS

    TTP

    Trial Keywords