A Study Of Oral GW572016 In Advanced Or Metastatic Non-Small Cell Lung Cancer
Condition: Lung Cancer, Non-Small Cell
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: GW572016 (lapatinib)
Intervention description: tyrosine kinase inhibitor
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: EGFR; ErbB1; ErbB2; metastatic; lapatinib; Her-2/neu; protein kinase inhibitor; BAC; GW572016; Advanced; NSCLC

Summary:

      This study was designed to evaluate and compare the efficacy of two dose schedules of an oral
      investigational drug for the treatment of advanced or metastatic non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent;

          -  Subjects must have histologically confirmed advanced (incurable stage IIIB or IV
             according to the International Staging System, [Mountain, 1997] Non-Small Cell Lung
             Cancer (NSCLC) at primary diagnosis or relapsed after curative-intent surgery. Only
             patients with either (1) the histological subtypes of adenocarcinoma with BAC
             (Bronchioloalveolar) features or pure BAC (as defined by the 1999 World Health
             Organization criteria) or, (2) never smokers (i.e. smoked <100 cigarettes in lifetime)
             with any histology of NSCLC (squamous, adenocarcinoma, lifetime) with any histology of
             NSCLC (squamous, adenocarcinoma,

          -  Patients can have had a maximum of 1 prior systemic therapy (chemotherapy or biologic
             therapy) for NSCLC that ended at least 3 weeks prior to enrollment. Patients that have
             had adjuvant cytotoxic chemotherapy that ended at least 3 months prior to enrollment
             are eligible. Prior surgery and radiotherapy are permitted. Patients should recover
             from acute side effects of radiation before enrollment (3-4 weeks). Concurrent
             radiotherapy is prohibited;

          -  Archived tumor tissue available for evaluation of genetic and intra-tumoral protein or
             mRNA expression levels of relevant biomarkers. A minimum of 10 slides of archived
             tumor tissue is required; however, 15 slides should be sent, if available. For
             patients diagnosed on the basis of pleural effusions, efforts should be made to
             provide as many slides as possible made with cells obtained from pleural aspirates.
             Results of biomarkers will not be used to determine subject eligibility for the study;

          -  Measurable lesion(s) according to RECIST (e.g., ≥15 mm with conventional techniques
             (medical photograph [skin or oral lesion], palpation, plain X-ray, CT, MRI, or ≥10 mm
             with spiral CT scan);

          -  At least 1 measurable lesion located outside of the prior radiation field or, if
             located within the prior field of irradiation, is increasing in size;

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;

          -  Life expectancy of ≥ 12 weeks;

          -  ≥ 18 years old;

          -  A female is eligible to enter and participate in this study if she is of: •
             Non-childbearing potential (i.e., women with functioning ovaries who have a current
             documented tubal ligation, women who had a hysterectomy, women who are
             post-menopausal, or women who have had both ovaries surgically removed); or •
             Childbearing potential (i.e., women with functioning ovaries and no documented
             impairment of oviductal or uterine function that would cause sterility). This category
             includes women with oligomenorrhea (even severe), women who are perimenopausal, and
             young women who have begun to menstruate. Women of childbearing potential must have a
             negative serum pregnancy test at screening, and agree to 1 of the following: a
             Complete abstinence from intercourse from 2 weeks prior to administration of the first
             dose of GW572016 until 28 days after the final dose of GW572016; or b Consistent and
             correct use of 1 of the following acceptable methods of birth control: 1. Male partner
             who is sterile prior to the female subject's entry into the study and is the sole
             sexual partner for that female subject; or 2. Implants of levonorgestrel 3. Injectable
             progestogen 4. Any intrauterine device (IUD) with a documented failure rate of less
             than 1% per year; or 5. Oral contraceptives (either combined or Progestogen only) 6.
             Barrier methods including diaphragm or condom with a spermicide

          -  Able to swallow and retain oral medication;

          -  Cardiac ejection fraction within the institutional range of normal as measured by
             echocardiogram. Subjects with known history of uncontrolled or symptomatic
             echocardiogram. Subjects with known history of uncontrolled or symptomatic angina,
             arrhythmias, or congestive heart failure are not eligible;

          -  Have adequate organ function as defined in Table 1 Baseline Laboratory Values for
             Inclusion;

          -  Subjects must complete all screening assessments as outlined in the protocol.

        Exclusion Criteria:

          -  Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel. Subjects with ulcerative colitis are also
             excluded;

          -  History of other malignancy. Subjects who have been disease-free for 5 years, or
             subjects with a history of completely resected non-melanoma skin cancer or
             successfully treated in situ carcinoma are eligible;

          -  Concurrent disease or condition that would make the subject inappropriate for study
             participation, or any serious medical disorder that would interfere with the subject's
             safety;

          -  Unresolved or unstable, serious toxicity from prior administration of another
             investigational drug;

          -  Active or uncontrolled infection;

          -  Dementia, altered mental status, or any psychiatric condition that would prohibit the
             understanding or rendering of informed consent;

          -  Uncontrolled angina, arrhythmias, or congestive heart failure. Patients whose symptoms
             are under control are eligible.

          -  Known history of or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis except for individuals who have previously treated CNS
             metastases, are asymptomatic, and have had no requirement for steroids or antiseizure
             medication for ≥ 3 months prior to study enrollment. Routine screening with CNS
             imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is
             required only if clinically indicated or if the subject has a history of CNS
             metastases;

          -  Concurrent cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy,
             biologic therapy, hormonal therapy, and tumor embolization).

          -  Concurrent treatment with an investigational agent or participation in another
             clinical trial

          -  Use of an investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of GW572016;

          -  Prior therapy with any ErbB1 and/or ErbB2 inhibitor;

          -  The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy
             to drugs chemically related to GW572016.

          -  Has taken/received the following inhibitors of CYP3A4 within the specified number of
             days prior to the first dose of study medication: Seven (7) days: antibiotics
             (clarithromycin, erythromycin, troleandomycin), antiretrovirals (delavirdine),
             protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir, amprenavir,
             lopinavir), systemic antifungals (itraconazole, ketoconazole, voriconazole,
             fluconazole (doses of 200 mg/day and above)), antidepressants (nefazodone,
             fluovoxamine), calcium channel blockers (verapamil, diltiazem), gastrointestinal
             (cimetidine, aprepitant), and grapefruit or its juice. Six (6) months: amiodarone.

          -  Has taken/received the following inducers of CYP3A4 within fourteen (14) days prior to
             the first dose of study medication: glucocorticoids (dexamethasone or dexamethasone
             equivalent dose > 1.5mg/day (see chart in Section 7.2 for conversion), anticonvulsants
             (phenytoin, carbamazepine, phenobarbital), efavirenz, nevirapine, antibiotics
             (rifampin (rifampicin), rifabutin, rifapentine), St. John's Wort and modafinil.