Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer
Condition: KRAS Gene Mutation; Recurrent Lung Non-Small Cell Carcinoma; Stage IV Lung Non-Small Cell Cancer AJCC v7
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Docetaxel; Laboratory Biomarker Analysis; Trametinib
Intervention description: Given IV; Correlative studies; Given PO
Intervention MeSH terms: Docetaxel; Trametinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  DISEASE RELATED CRITERIA: Patients must have pathologically confirmed KRAS mutation
             (at codon 12, 13 and 61) 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 Act (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,
             leptomeningeal carcinomatosis or spinal cord compression 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 2 days 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;
             treatment with an immune therapy or targeted therapy for advanced disease will be
             considered a separate regimen and will count toward the prior regimens; maintenance
             therapy will not be counted as a separate regimen; 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 recurrence 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 any chemotherapy,
             biologic agent, or any investigational agent within 14 days prior to registration.
             Patients must have recovered from any adverse events to Common Terminology Criteria
             for Adverse Events (CTCAE) grade 0-1 prior to registration

          -  PRIOR/CONCURRENT THERAPY CRITERIA: Prior treatment with an anti-PD-1 or anti-PDL1 is
             not required

          -  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 =< CTCAE 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 7 days must have
             elapsed since last radiation treatment; patients must have recovered from any adverse
             events from prior radiation therapy to =< 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; biopsies and central
             IV access placement are not considered major surgery

          -  PRIOR/CONCURRENT THERAPY CRITERIA: Because the composition, pharmacokinetics (PK), and
             metabolism of many herbal supplements are unknown, the concurrent use of all herbal
             supplements is prohibited during the study (including but not limited to St. John's
             wort, kava, ephedra [ma huang], ginko biloba, dehydroepiandrosterone [DHEA], yohimbe,
             saw palmetto, or ginseng)

          -  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 or that
             may alter absorption such as malabsorption syndromes or gastric resection

          -  CLINICAL/LABORATORY CRITERIA: Patient must not have prior history of interstitial lung
             disease or pneumonitis

          -  CLINICAL/LABORATORY CRITERIA: Patients must not have history of significant co-morbid
             illness inclusive of but not restricted to New York Heart Association class II,
             congestive cardiac failure, uncontrolled hypertension, history of myocardial
             infarction, unstable angina, coronary angioplasty, stenting 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 (using the Bazett's formula) on electrocardiogram (ECG) performed within 42 days
             prior to registration; history or evidence of current clinically significant
             uncontrolled arrhythmias are not eligible; however, patients with controlled atrial
             fibrillation for > 30 days prior to randomization are eligible; patients must not have
             atrial fibrillation > grade 2 on the screening ECG; patients with CTCAE grade 1-2
             atrial fibrillation on their screening ECG must have a second ECG performed prior to
             registration and more than 30 days from the screening ECG (either before or after)
             with the most recent ECG showing stable or improving grade of atrial fibrillation

          -  CLINICAL/LABORATORY CRITERIA: Patients must have a left ventricular ejection fraction
             (LVEF) >= institutional lower limit of normal (ILLN) by echocardiography (ECHO) or
             multi-gated acquisition scan (MUGA) within 42 days prior to registration

          -  CLINICAL/LABORATORY CRITERIA: Patients must not have untreated or unresolved
             retinopathy or have a history (or current evidence) of retinal vein occlusion
             determined by an ophthalmology exam within 42 days prior to registration

          -  CLINICAL/LABORATORY CRITERIA: Patients must not have an immediate or delayed
             hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib,
             or excipients, or to dimethyl sulfoxide (DMSO) or other agents used in the study

          -  CLINICAL/LABORATORY CRITERIA: Patients must not have a known history of active
             hepatitis B or C infection (defined as presence of hepatitis [Hep] B surface antigen
             [sAg] and/or Hep B deoxyribonucleic acid [DNA] and/or Hep C ribonucleic acid [RNA]);
             patients must not have a known history of 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 due to the risk
             of fetal or nursing infant harm; women/men of reproductive potential must have agreed
             to use an effective contraceptive method (hormonal or barrier method of birth control;
             abstinence) prior to study entry, during the study participation and for 4 months
             after the last dose of the drug; 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 optional participation in
             banking of specimens for future research

          -  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