Clinical trial NCT00095940 (phase 1/phase 2, status: completed)
Conditions: recurrent childhood anaplastic astrocytoma, recurrent childhood brain stem glioma, recurrent childhood ependymoma, recurrent childhood giant cell glioblastoma, recurrent childhood glioblastoma, recurrent childhood gliosarcoma, recurrent childhood medulloblastoma, recurrent childhood oligodendroglioma
ICD codes: C84.67, C84.77, C84.7A, C84.60, C84.70, C84.62, C84.66, G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2
Drugs: lapatinib ditosylate
SMILES: CS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C1
Eligibility criteria:

        Inclusion Criteria:

          -  PHASE I TRIAL:

               -  All patients with recurrent or refractory malignant CNS tumors; a histological
                  diagnosis of malignant CNS tumor from either the initial presentation or at the
                  time of recurrence is required for all patients, but those with brain stem
                  gliomas

        MOLECULAR BIOLOGY TRIAL:

          -  Patients must have recurrent or refractory disease with a histological diagnosis from
             either the initial presentation or at the time of recurrence of one of the following:

               -  Recurrent or refractory medulloblastoma/PNET

               -  Recurrent or refractory high grade glioma, (anaplastic astrocytoma, glioblastoma
                  multiforme, gliosarcoma, anaplastic oligodendroglioma)

               -  Recurrent or refractory ependymoma

          -  Patients for whom surgical resection is clinically indicated and are amenable to
             receiving GW572016 for 7-14 days prior to their resection

        PHASE II TRIAL:

          -  Patients must have recurrent or refractory disease with a histological diagnosis from
             either the initial presentation or at the time of recurrence of one of the following:

               -  Recurrent or refractory medulloblastoma/PNET,

               -  Recurrent or refractory high grade glioma, (anaplastic astrocytoma, glioblastoma
                  multiforme, gliosarcoma, anaplastic oligodendroglioma)

               -  Recurrent or refractory ependymoma

          -  Patients must have measurable disease

               -  Patients with neurological deficits should have deficits that are stable for a
                  minimum of 1 week prior to registration

               -  Karnofsky performance scale (KPS for > 16 yrs of age) or Lansky performance score
                  (LPS for =< 16 years of age) >= 50 assessed within two weeks prior to
                  registration

               -  Evidence of recovery from prior chemotherapy; no myelosuppressive anticancer
                  chemotherapy within 3 weeks and no biological therapy or other
                  non-myelosuppressive investigational agent =< 7 days prior to study registration
                  (6 weeks if a nitrosourea or mitomycin C agent) prior to registration

               -  >= 3 months prior to registration for craniospinal irradiation (>= 18 Gy); >= 4
                  weeks for local radiation to primary tumor; and >= 2 weeks prior to registration
                  for focal irradiation to symptomatic metastatic sites

               -  >= 6 months prior to registration for allogeneic bone marrow transplants and >= 3
                  months prior to registration for autologous bone marrow/stem cell transplants

               -  Patients with seizure disorder may be enrolled if well controlled; patients
                  receiving enzyme inducing anticonvulsants are not eligible for this study;
                  patients must be off EIACD for at least 2 weeks prior to registration

               -  Patients who are receiving corticosteroids must be on a stable or decreasing dose
                  for at least 1 week prior to registration; patients enrolled in the molecular
                  biology and phase II components of the study will not be stratified based on
                  steroid use; however, use of steroids should be reported as a concomitant
                  medication in the database; in the phase I component of the study, patients on
                  corticosteroids will be eligible for stratum 2 of the study; patients with ACTH
                  deficiency who are on physiological replacement doses of hydrocortisone (or other
                  corticosteroid) will be eligible for stratum 1 of the study

               -  Off all colony forming growth factor(s) >= 2 weeks prior to registration (G-CSF,
                  GM-CSF, Erythropoietin)

               -  Patients must not have received:

          -  CYP3A4 inhibitors within seven (7) days prior to registration on protocol and for the
             duration of the study; however, amiodarone, another CYP3A4 inhibitor, should have been
             discontinued 6 months prior to registration and for the duration of the study

          -  CYP3A4 inducers within fourteen (14) days prior to registration and for the duration
             of the study

          -  Cimetidine within 48 hours prior to registration and for the duration of the study

               -  Patients must be in adequate general condition for study

               -  Absolute neutrophil count >= 1000/microliter

               -  Platelets >= 100,000/microliter (transfusion independent)

               -  Hemoglobin >= 8.0 g/dL (transfusion independent)

               -  Serum creatinine =< 1.5 times upper limit of institutional normal for age or GFR
                  >= 70 ml/min/1.73m^2

               -  Bilirubin =< 1.5 times upper limit of normal for age

               -  SGPT (ALT) < 2.5 x institutional upper limit of normal

               -  Albumin >= 2 g/dL

               -  No overt renal, hepatic, biliary, cardiac or pulmonary disease

               -  Adequate cardiac function, assessed within 2 weeks prior to registration, defined
                  as: shortening fraction of >= 27% by echocardiogram, or ejection fraction >= 50%
                  by gated radionuclide study

               -  Adequate pulmonary function, assessed within 2 weeks prior to registration,
                  defined as: no evidence of dyspnea at rest, no exercise intolerance, and a pulse
                  oximetry > 94% if there is clinical indication for determination

               -  Patients of childbearing or child fathering potential must be willing to use a
                  medically acceptable form of birth control, which includes abstinence, while
                  being treated on this study

               -  Signed informed consent according to institutional guidelines must be obtained

        Exclusion Criteria:

          -  Patients with any significant medical illnesses that, in the investigator's opinion,
             cannot be adequately controlled with appropriate therapy or would compromise the
             patient's ability to tolerate this therapy

          -  Patients with any disease that would obscure toxicity or dangerously alter drug
             metabolism

          -  Patients with uncontrolled infection