Clinical Trials /

Molecularly Targeted Therapy in Treating Patients With BRAF Wild-type Melanoma That is Metastatic

NCT02094872

Description:

This phase II trial studies how well molecularly targeted therapy works in treating patients with melanoma that has spread to other parts of the body. Patients must have received or do not qualify for prior immunotherapy. Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Molecularly targeted therapy works by treating patients with substances that kill cancer cells by targeting key molecules involved in cancer cell growth.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Molecularly Targeted Therapy</span> in Treating Patients With <span class="go-doc-concept go-doc-biomarker">BRAF</span> Wild-type <span class="go-doc-concept go-doc-disease">Melanoma</span> That is Metastatic

Title

  • Brief Title: Molecularly Targeted Therapy in Treating Patients With BRAF Wild-type Melanoma That is Metastatic
  • Official Title: Stand Up to Cancer Consortium Genomics-Enabled Medicine for Melanoma (G.E.M.M.): Using Molecularly-Guided Therapy for Patients With BRAF Wild-Type (BRAFwt) Metastatic Melanoma
  • Clinical Trial IDs

    NCT ID: NCT02094872

    ORG ID: HIC # 1408014446

    NCI ID: NCI-2014-00670

    Trial Conditions

    Recurrent Melanoma

    Stage IIIA Melanoma

    Stage IIIB Melanoma

    Stage IIIC Melanoma

    Stage IV Melanoma

    Trial Interventions

    Drug Synonyms Arms
    molecularly targeted therapy Doxorubicin, Rubex Arm I (molecularly targeted therapy)

    Trial Purpose

    This randomized phase II trial studies how well molecularly targeted therapy works in
    treating patients with melanoma that has spread to other parts of the body. Patients must
    have received or do not qualify for prior immunotherapy. Targeted therapy is a type of
    treatment that uses drugs or other substances to identify and attack specific types of
    cancer cells with less harm to normal cells. Molecularly targeted therapy works by treating
    patients with substances that kill cancer cells by targeting key molecules involved in
    cancer cell growth.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the difference in best overall response rate (BORR) between patients treated
    with personalized targeted treatment vs. those treated with physician's choice of standard
    therapy.

    SECONDARY OBJECTIVES:

    I. To evaluate the safety of performing individualized drug therapy (including novel agents
    and commercially-available agents) in the context of a personalized medicine clinical trial.

    II. To continually assess the process of enrolling and treating patients to a personalized
    medicine clinical trial by acquiring blood and tissue, genetically characterizing v-raf
    murine sarcoma viral oncogene homolog B (BRAF) wild type (wt) metastatic melanoma tumors,
    identifying a list of potential driver mutations, and treating each patient within a 5-week
    time frame.

    III. To determine the difference in progression free survival (PFS) between patients treated
    with personalized targeted treatment vs. those treated with physician's choice therapy.

    IV. To determine the BORR in specific target-drug matchings (those more frequent).

    V. To iteratively refine and standardize a set of statistical and informatics methodologies
    for matching treatments to the patient's tumor, based on their molecular profile.

    OUTLINE: Patients are randomized to 1 of 2 treatment arms.

    ARM I: Patients undergo collection of tissue and blood samples for deoxyribonucleic acid
    (DNA) and ribonucleic acid (RNA) analysis via sequencing. Based on the results of the DNA
    and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the
    absence of disease progression or unacceptable toxicity.

    ARM II: Patients undergo collection of tissue and blood samples for DNA and RNA analysis via
    sequencing. Patients receive physician's choice standard of care therapy. Treatment
    continues in the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up for 1 year.

    Trial Arms

    Name Type Description Interventions
    Arm I (molecularly targeted therapy) Experimental Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. molecularly targeted therapy
    Arm II (standard of care therapy) Active Comparator Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Patients receive physician's choice standard of care therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

    Inclusion Criteria:

    - Patient with metastatic or locally advanced and unresectable BRAF wild-type melanoma
    who have either progressed following previous treatment of immunotherapy, or are not
    eligible for immunotherapy; pts. are defined as "BRAF wild-type" if they test
    negative for V600 mutations based on a Clinical Laboratory Improvement Amendments
    (CLIA) certified assay

    - Patients must have tumor accessible by interventional radiology or surgical
    intervention and suitable for biopsy (BX) with 5-6 passes of a 16 or 18 gauge needle
    for core BX (defined as at least 1 cm^3 tumor/50 mg accessible for BX), and must
    agree to undergo up to two surgical resections/biopsies to collect tumor for research
    purposes; the first of these biopsies will occur at the beginning of the study, prior
    to genetic analysis and Rx; the second BX will be performed at the time of DZ
    progression/end of study should funding be available

    - Patients must have measurable DZ (per Response Evaluation Criteria in Solid Tumors
    [RECIST] version 1.1 [v1.1] criteria), defined as at least one lesion that can be
    accurately measured in at least one dimension (longest diameter to be recorded for
    non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional
    techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic
    resonance imaging (MRI), or a subcutaneous or superficial lesion that can be measured
    with calipers by clinical exam; for lymph nodes, the short axis must be >= 15 mm

    - Previous therapies: prior radiation therapies, immunotherapies, and investigational
    therapies are allowed as follows.

    - Radiation: prior radiation therapy (RT) is allowed with the following
    conditions:

    - Patients who have received minimal RT (=< 5% of their total marrow volume)
    must have completed it >= 2 weeks prior to the initiation of study Rx

    - Patients who have received RT that constituted > 5% but < 50% of their
    total marrow volume must have completed it >= 4 weeks prior to the
    initiation of study treatment

    - Patients who have received prior radiation to 50% or more of their total
    marrow volume will be excluded

    - Patients may be biopsied while undergoing RT as long as BX site is not in
    the radiation portal; however, they still have to wait the required amount
    of time from radiation to treatment even though the tumor board may have
    already occurred and a treatment plan assigned

    - Other therapies: prior investigational or targeted therapies and immunotherapies
    may be allowed following discussion with the PI (PI); if the PI deems the prior
    treatment acceptable, patients must not have received these therapies for 28
    days or five half-lives of the drug (whichever is lesser) prior to the
    initiation of study treatment and must have full recovery from any acute effects
    of these therapies; prior therapy with mitogen-activated protein kinase (MEK)
    inhibitors will not be allowed

    - Patients with chronic grade 1 or 2 toxicity may be eligible at the discretion of the
    PI if the condition has been stable, and not worsening, for at least 30 days; pts.
    with ongoing alopecia of any grade will be eligible

    - Patient must have a life expectancy of >= 3 months, as estimated by the treating
    oncologist

    - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =<
    2

    - Hemoglobin >= 9 g/dL

    - Leukocytes >= 3,000/microliter (mcL)

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

    - Platelets (PLT) >= 100,000/mcL

    - Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN); if liver
    metastases are present, =< 5 x ULN

    - Alanine aminotransferase (ALT) =< 2.5 x ULN; if liver metastases are present, =< 5 x
    ULN

    - Bilirubin =< 1.5 x ULN

    - Creatinine =< 1.5 x ULN OR calculated or measured creatinine clearance >= 50
    mL/min/1.73 m^2 for pts. with creatinine above institutional normal

    - If available, pt. must agree to provide archival tissue for research purposes (either
    archival paraffin tissue block or 10 unstained slides of a primary or metastatic
    melanoma lesion) prior to enrollment; samples should be shipped within 1 month after
    enrollment

    - Patient agrees to having a blood sample (a minimum of 10 mL, with 20 mL preferred)
    drawn and analyzed to compare their normal genetic profile to that of their tumor
    sample

    - Patient must be able to tolerate oral medication

    - Women of child-bearing potential and men must agree to use 2 forms of adequate
    contraception (hormonal or barrier method of birth control; abstinence) for the
    duration of study participation, and for four months following completion of study
    therapy; should a woman become pregnant or suspect she is pregnant while
    participating in this study, she should inform her treating physician immediately;
    women who become pregnant must immediately discontinue Rx with any study therapy;
    male pts. should avoid impregnating a female partner; male pts., even if surgically
    sterilized, (i.e. post-vasectomy) must agree to one of the following: practice
    effective barrier contraception during the entire study Rx period and through 4
    months after the last dose of study drug, or completely abstain from sexual
    intercourse

    - Patient must have the ability to understand and the willingness to sign a written
    informed consent document

    - Patient must be willing and able to comply with the protocol for the duration of the
    study, including attending scheduled visits, examinations, the BX procedure, and
    having their tumor and blood molecularly characterized

    - Patient understands if he or she is randomized to receive molecularly guided
    treatment, they must meet all inclusion and exclusion criteria in the drug specific
    appendix for which they were randomized

    Exclusion Criteria:

    - Patients with peripheral neuropathy >= grade 2 are not permitted unless discussed
    with the PI and only in unique circumstances (i.e. unilateral neuropathy due to
    trauma)

    - Patient has DZ that tests positive for BRAF V600 mutations based on the results of a
    CLIA certified assay

    - Patients with active infection at time of BX

    - Patients with any evidence of severe or uncontrolled systemic DZ(s) including known
    cases of hepatitis B or C or human immunodeficiency virus (HIV); screening for
    chronic conditions is not required, although pts. known to have such conditions at
    screening should not be included

    - Any patient requiring chronic maintenance of red blood cell, white blood cell or
    granulocyte counts through the use of blood transfusions or growth factor support
    (e.g. Neulasta, Neupogen)

    - Patients with a prior history of seizures within the past year unrelated to brain
    metastases

    - Patients with known active progressive brain metastases; pts. with prior treated
    brain metastases are allowed, providing that they were not accompanied by seizures
    within the past year and that a baseline brain MRI scan prior to study entry
    demonstrates no current evidence of active brain metastases; all pts. with prior
    treated brain metastases must be stable for > 1 months after treatment and off
    steroid treatment prior to study enrollment

    - Patients receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or
    hormonal other than for replacement) except for medications that are prescribed for
    supportive care but may potentially have an anti-cancer effect (i.e. megestrol
    acetate, bisphosphonates); these medications must have been started >= month prior to
    enrollment on this study; pts. may be on low molecular weight heparin or direct
    factor Xa inhibitors

    - Patients with any clinically significant medical condition which, in the opinion of
    the investigator, makes it undesirable for the pt. to participate in the study or
    which could jeopardize compliance with protocol requirements including, but not
    limited to: ongoing or active infection, significant uncontrolled hypertension, or
    severe psychiatric illness/social situations

    - Patients with preexisting cardiac conditions, including uncontrolled or symptomatic
    angina, arrhythmias, or congestive heart failure will not be eligible

    - Patients with left ventricular ejection fraction (LVEF) < 45% will not be eligible

    - Patients with either of the following within 6 months before the first dose of study
    treatment:

    - Stroke (including transient ischemic attack [TIA], or other ischemic event)

    - Myocardial infarction

    - Patients with acute gastrointestinal bleeding within 1 month of study entry

    - Patients who have, at screening, corrected QT interval using Fridericia's formula
    (QTcF) >= 450 msec for males and QTcF >= 470 for females

    - Patients with a co-morbid condition(s) that, in the opinion of the investigator,
    prevents safe surgery/BX procedure

    - Patients with malabsorption syndrome or other condition that would interfere with
    intestinal absorption or ability to swallow oral medication

    - Pregnant or nursing women; breastfeeding must be discontinued prior to Rx

    - Patients who have received organ transplant

    - Patients who have had major surgery within 14 days of study enrollment

    - Patients diagnosed or treated for another malignancy within 3 years of enrollment,
    with the exception of complete resection of basal cell carcinoma or squamous cell
    carcinoma of the skin, or an in situ malignancy

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    BORR

    Secondary Outcome Measures

    PFS

    Trial Keywords