Dose-Dense Temozolomide + Lapatinib for Recurrent Ependymoma
Condition: Brain Tumors; Spinal Cord Tumors
MeSH terms: Neoplasms; Brain Neoplasms; Ependymoma; Spinal Cord Neoplasms
Intervention: Temozolomide; Lapatinib
Intervention description: Starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle.; Starting dose 1250 mg daily by mouth.
Intervention MeSH terms: Temozolomide; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Brain Tumor; Central Nervous System; CNS; Spinal Cord Tumor; Anaplastic Ependymoma; Supratentorial Ependymoma; Infratentorial Ependymoma; Spinal Cord Ependymoma; Lapatinib; GW572016; Temozolomide; Temodar

Summary:

      The goal of this clinical research study is to learn if lapatinib when given in combination
      with temozolomide can help to control ependymoma that has come back after treatment. The
      safety of this combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically proven ependymoma or anaplastic ependymoma. There must be pathologic or
             imaging confirmation of tumor progression or regrowth. The patients histologic
             diagnosis must be confirmed on Central Pathology Review prior to registration Step 2.

          2. History and physical examination, including neurologic examination, within 2 weeks
             prior to registration.

          3. Patients must be able to undergo brain or spine magnetic resonance imaging (MRI) scans
             with intravenous gadolinium, based on tumor location(s) within 14 days prior to
             registration.

          4. Patients must be on a steroid dose that has been stable or decreasing for at least 5
             days. If the steroid dose is increased between the date of imaging and registration, a
             new baseline MRI is required.

          5. Karnofsky performance status >/= 70

          6. Age >/= 18

          7. Complete blood count (CBC)/differential obtained within 14 days prior to registration,
             with adequate bone marrow function defined as follows: 1) Absolute neutrophil count
             (ANC) >/= 1,500/mm^3. 2) Platelets >/= 100,000 cells/mm^3. 3) Hemoglobin >/= 10.0
             gm/dL (Note: The use of transfusion or other intervention to achieve Hgb >/= 10.0 is
             acceptable). 4) White blood cell count (WBC) >/= 3,000/mcL.

          8. Adequate liver function within 14 days prior to registration, defined as follows:
             serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] < 2.5
             times the upper limit of normal, Bilirubin </= 1.6 mg/dL

          9. Adequate renal function within 14 days prior to registration, defined as follows:
             Creatinine < 1.7 mg/dL

         10. Patients must have recovered from the toxic effects of prior therapy, and there must
             be a minimum time of: 1) 28 days from the administration of any investigational agent.
             2) 28 days from administration of prior cytotoxic therapy with the following
             exceptions: (a) 14 days from administration of vincristine. (b) 42 days from
             administration of nitrosoureas. (c) 21 days from administration of procarbazine.

         11. ( 11. continued) 3) 7 days from administration of non-cytotoxic agents [e.g.,
             interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not
             count)]. 4) 28 days from prior radiation therapy.

         12. Patients must have recovered from the effects of surgery and a minimum of 14 days must
             have elapsed from the day of surgery to the day of registration. For core or needle
             biopsy, a minimum of 7 days must have elapsed prior to registration.

         13. Residual disease following resection of recurrent tumor is not mandated for
             eligibility into the study. To best assess the extent of residual disease
             post-operatively, an MRI should be done no later than 96 hours in the immediate
             postoperative period or at least 4 weeks postoperatively, within 14 days prior to
             registration. If the " within 96-hour of surgery " scan is more than 14 days before
             registration, the scan needs to be repeated.

         14. Patients must sign study-specific informed consent and authorization for the release
             of their protected health information prior to registration. Patients must be
             registered in the MD Anderson Cancer Center Office of Multicenter Clinical Research
             (MDACC OMCR) database prior to treatment with study drug.

         15. Women of childbearing potential must have a negative beta-human chorionic gonadotropin
             (HCG) pregnancy test documented within 14 days prior to registration.

         16. Women of childbearing potential and male participants must practice adequate
             contraception

         17. All patients must have an left ventricular ejection fraction (LVEF) measurement of at
             least 50% by Echo or MUGA (if clinically indicated) within 14 days prior to
             registration. The method used for LVEF assessment in an individual subject must be the
             same throughout the trial.

        Exclusion Criteria:

          1. Prior invasive malignancy that is not the ependymoma (except non-melanomatous skin
             cancer or carcinoma in situ of the cervix) unless the patient has been disease free
             and off therapy for that disease for a minimum of 3 years

          2. Transmural myocardial infarction or unstable angina within 3 months prior to study
             registration

          3. Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations
             of >/= 2 mm using the analysis of an electrocardiography (EKG) performed within 14
             days prior to registration

          4. New York Heart Association grade II or greater congestive heart failure requiring
             hospitalization within 12 months prior to registration

          5. History of stroke or transient ischemic attack within 3 months prior to registration.

          6. Inadequately controlled hypertension (systolic blood pressure > 140 mm Hg and/or
             diastolic blood pressure > 90 mm Hg despite antihypertensive medication)

          7. History of cerebral vascular accident (CVA) within 3 months prior to registration

          8. Serious and inadequately controlled cardiac arrhythmia

          9. Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)

         10. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of
             registration

         11. Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease
             Control and Prevention (CDC) definition; note, however, that HIV testing is not
             required for entry into this protocol. The need to exclude patients with acquired
             immunodeficiency syndrome (AIDS) from this protocol is necessary because the
             treatments involved in this protocol may be significantly immunosuppressive.

         12. Pregnant or nursing women because of concern of fetal/infant exposure to these agents

         13. Any condition that impairs ability to swallow pills (e.g., gastrointestinal tract
             disease resulting in an inability to take oral medication or a requirement for
             intravenous (IV) alimentation, prior surgical procedures affecting absorption, active
             peptic ulcer disease).

         14. Patients cannot be receiving enzyme-inducing anti-epileptic Drugs (EIAEDs) nor any
             other Image result for CYP3A4 Cytochrome P450 3A4 (CYP3A4) inducers such as rifampin
             or St. John's wort beginning at least 14 days prior to registration Step 2.

         15. Patients cannot be receiving CYP3A4 inhibitors beginning at least 7 days prior to
             registration Step 2.

         16. Patients must not have current active hepatic or biliary disease (with exception of
             patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver
             disease per investigator assessment).

         17. Patients cannot be receiving HAART (Highly Active Anti-Retroviral Therapy) therapy.