Clinical Trials /

Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer

NCT02642042

Description:

This phase II trial studies how well trametinib and docetaxel work in treating patients with stage IV KRAS mutation positive non-small cell lung cancer or cancer that has come back. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trametinib with docetaxel may work better in treating non-small cell lung cancer.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Trametinib</span> and Docetaxel in Treating Patients With Recurrent or Stage IV Non-small Cell Lung Cancer

Title

  • Brief Title: Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV Non-small Cell Lung Cancer
  • Official Title: A Phase II Trial of Trametinib With Docetaxel in Patients With KRAS Mutation Positive Non-small Cell Lung Cancer (NSCLC) and Progressive Disease Following One or Two Prior Systemic Therapies
  • Clinical Trial IDs

    NCT ID: NCT02642042

    ORG ID: NCI-2015-02250

    NCI ID: NCI-2015-02250

    Trial Conditions

    Recurrent Non-Small Cell Lung Carcinoma

    Stage IV Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Docetaxel Docecad, RP56976, Taxotere, Taxotere Injection Concentrate Treatment (trametinib, docetaxel)
    Trametinib GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist Treatment (trametinib, docetaxel)

    Trial Purpose

    This phase II trial studies how well trametinib and docetaxel work in treating patients with
    stage IV non-small cell lung cancer or cancer that has come back. Trametinib may stop the
    growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in
    chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells,
    either by killing the cells, by stopping them from dividing, or by stopping them from
    spreading. Giving trametinib with docetaxel may work better in treating non-small cell lung
    cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To evaluate the response rate (confirmed and unconfirmed) to trametinib plus docetaxel in
    the entire study population of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation
    positive non-small cell lung cancer (NSCLC) patients following one or two prior systemic
    therapies.

    SECONDARY OBJECTIVES:

    I. To evaluate if trametinib plus docetaxel is consistent with promise of activity measured
    by the response rate in G12C KRAS mutation positive NSCLC patients following one or two
    prior systemic therapies.

    II. To assess the response rate of this combination in non-G12C KRAS mutation positive NSCLC
    patients.

    III. To assess progression-free survival within the G12C and non-G12C KRAS positive
    subgroups and the entire study population.

    IV. To evaluate the toxicity of the regimen. V. To assess overall survival within G12C
    positive patients, non-G12C positive patients, and the entire study population.

    VI. To evaluate the response rates in the presence of comutations p53 and LKB1. VII. To bank
    specimens for future research.

    TERTIARY OBJECTIVES:

    I. To evaluate the response rates in the presence of comutations p53 and LKB1. II. To bank
    specimens for future research.

    OUTLINE:

    Patients receive trametinib orally (PO) on days 1-21. Patients also receive docetaxel
    intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease
    progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up every 6 months for 3 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (trametinib, docetaxel) Experimental Patients receive trametinib PO on days 1-21. Patients also receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Docetaxel, Trametinib

    Eligibility Criteria

    Inclusion Criteria:

    - DISEASE RELATED CRITERIA: Patients must have pathologically confirmed KRAS mutation
    positive non-small cell lung cancer (NSCLC) that is stage IV or recurrent; the
    specific subtype of KRAS mutation must be known; KRAS mutation testing must have been
    performed in a Clinical Laboratory Improvement Amendments (CLIA) certified
    laboratory; CLIA certified commercially available tests are acceptable

    - DISEASE RELATED CRITERIA: Patients must have measurable disease documented by
    computed tomography (CT) or magnetic resonance imaging (MRI) within 28 days prior to
    registration; the CT from a combined positron emission tomography (PET)/CT may be
    used only if it is of diagnostic quality; non-measurable disease must be assessed
    within 42 days prior to registration; all known sites of disease must be assessed and
    documented on the baseline tumor assessment form (Response Evaluation Criteria in
    Solid Tumors [RECIST 1.1])

    - DISEASE RELATED CRITERIA: Patients must not have known brain metastases unless: (1)
    metastases have been locally treated (including stereotactic body radiation therapy
    [SBRT], whole brain radiotherapy [WBRT], and surgical resection) and have remained
    clinically controlled and asymptomatic for at least 14 days following treatment and
    prior to registration, AND (2) patient has no residual neurological dysfunction and
    has been off corticosteroids for at least 24 hours prior to registration

    - PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have documented progressive cancer
    following at least one but no more than two prior regimens of systemic therapy for
    lung cancer, one of which must have been platinum based combination chemotherapy.
    Patients must not have received any chemotherapy drug within three weeks prior to
    registration. Patients must not have received any biologic agent within two weeks
    prior to registration

    - PRIOR/CONCURRENT THERAPY CRITERIA: Adjuvant chemotherapy or chemotherapy administered
    as part of concurrent chemotherapy and radiation therapy for the treatment of lung
    cancer will not count as a prior regimen of systemic therapy as long as recurrent of
    patient's lung cancer occurred more than 12 months after the last day of chemotherapy

    - PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have received prior docetaxel;
    patients must not have received therapy with a drug known to be either a
    mitogen-activated protein kinase (MEK) inhibitor or a phosphatidylinositol 3 kinase
    (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of
    rapamycin (mTOR) pathway inhibitor

    - PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have recovered from any adverse
    effects from prior therapy (except alopecia) to =< grade 1 prior to registration

    - PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have had prior radiation therapy as
    long as it has not affected greater than 25% of the bone marrow and at least one
    measurable lesion is outside the area of prior radiation; at least one week must have
    elapsed since last radiation treatment; patients must have recovered from any adverse
    events from prior radiation therapy to =< Common Terminology Criteria For Adverse
    Events (CTCAE) grade 1

    - PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have had a major surgery within
    28 days prior to registration; patients must have recovered from any adverse effects
    of prior surgery to the satisfaction of the treating physician

    - CLINICAL/LABORATORY CRITERIA: Patients must have Zubrod performance status of 0-2

    - CLINICAL/LABORATORY CRITERIA: Absolute neutrophil count (ANC) >= 1500/mcL; these
    results must be obtained within 28 days prior to registration

    - CLINICAL/LABORATORY CRITERIA: Platelet count >= 100,000/mcL; these results must be
    obtained within 28 days prior to registration

    - CLINICAL/LABORATORY CRITERIA: Hemoglobin >= 9 grams/dl; these results must be
    obtained within 28 days prior to registration

    - CLINICAL/LABORATORY CRITERIA: Total bilirubin =< 1.5 x institutional upper limit of
    normal (IULN); these results must be obtained within 28 days prior to registration

    - CLINICAL/LABORATORY CRITERIA: Aspartate aminotransferase (AST) and alanine
    aminotransferase (ALT) =< 2.5 x IULN (or =< 5 x IULN for patients with known liver
    metastases); these results must be obtained within 28 days prior to registration

    - CLINICAL/LABORATORY CRITERIA: Serum creatinine =< 1.5 x IULN OR measured or
    calculated creatinine clearance >= 40 mL/min; this result must have been obtained
    within 28 days prior to registration

    - CLINICAL/LABORATORY CRITERIA: Patients must be able to swallow oral medications and
    must not have a gastro-intestinal disorder with diarrhea as a major symptom

    - CLINICAL/LABORATORY CRITERIA: Patients must not have history of significant co-morbid
    illness inclusive of but not restricted to uncontrolled congestive cardiac failure,
    uncontrolled hypertension, history of myocardial infarction or cerebrovascular
    accident within 6 months prior to registration or any other illness that in the
    assessment of the treating physician would compromise the ability of the patient to
    participate in this study

    - CLINICAL/LABORATORY CRITERIA: Patients must have corrected QT (QTc) interval =< 480
    msec on electrocardiogram performed within 42 days prior to registration

    - CLINICAL/LABORATORY CRITERIA: Patients must not have untreated or unresolved
    retinopathy

    - CLINICAL/LABORATORY CRITERIA: Patients must not have a known history of active
    hepatitis B infection (defined as presence of hepatitis [Hep] B surface antigen [sAg]
    and/or Hep B deoxyribonucleic acid [DNA]), active hepatitis C infection (defined as
    presence of Hep C ribonucleic acid [RNA]), or human immunodeficiency virus (HIV)
    seropositivity

    - CLINICAL/LABORATORY CRITERIA: No other prior malignancy is allowed except for the
    following: adequately treated basal cell or squamous cell skin cancer, in situ
    cervical cancer, adequately treated stage I or II cancer from which the patient is
    currently in complete remission, or any other cancer from which the patient has been
    disease free for three years; patients with localized prostate cancer who are being
    followed by an active surveillance program are also eligible

    - CLINICAL/LABORATORY CRITERIA: Patients must not be pregnant or nursing; women/men of
    reproductive potential must have agreed to use an effective contraceptive method; a
    woman is considered to be of "reproductive potential" if she has had menses at any
    time in the preceding 12 consecutive months; in addition to routine contraceptive
    methods, "effective contraception" also includes heterosexual celibacy and surgery
    intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined
    as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at
    any point a previously celibate patient chooses to become heterosexually active
    during the time period for use of contraceptive measures outlined in the protocol,
    he/she is responsible for beginning contraceptive measures

    - SPECIMEN SUBMISSION CRITERIA: Patients must be offered participation in translational
    medicine studies and banking

    - REGULATORY CRITERIA: Patients must be informed of the investigational nature of this
    study and must sign and give written informed consent in accordance with
    institutional and federal guidelines

    - REGULATORY CRITERIA: As a part of the Oncology Patient Enrollment Network (OPEN)
    registration process the treating institution's identity is provided in order to
    ensure that the current (within 365 days) date of institutional review board approval
    for this study has been entered in the system

    Minimum Eligible Age: N/A

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Response rate (confirmed and unconfirmed complete and partial responses) in all KRAS mutant patients (both those with G12C mutations and those with non-G12C mutations)

    Secondary Outcome Measures

    Incidence of toxicity graded according to the National Cancer Institute CTCAE version 4.0

    Overall survival

    Progression free survival

    Response rate in patients with a G12C mutation

    Trial Keywords