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Study Summary
No. CERN08-02:.......Brain; CNS......Mark R. Gilbert......Neuro Oncology
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Study Summary Title
Study Summary
Number:
CERN08-02
Study Title:A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma
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Physician New Patient Referral
Name:Mark R. GilbertPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Neuro OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2883
Contact us about clinical trials
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General Information
Disease Group:Brain
CNS
Supported By:Collaborative Ependymoma Research Network
Phase of Study:Phase IIReturn
Visit:
Every 8 weeks
Treatment
Agents:
Lapatinib
Temozolomide
Home Care:Patient will take temozolomide and lapatinib orally at home
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
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.
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Study Objectives / Outcomes
Primary Objective
  • To determine the efficacy of the combination of temozolomide and lapatinib in recurrent brain ependymoma and anaplastic ependymoma as measured by median progression-free survival.
Secondary Objectives
  • To determine the efficacy of the combination of lapatinib and temozolomide as measured by objective response in patients with measurable disease.
  • To determine the adverse event profile and tolerability of the combination of lapatinib and temozolomide in patients with recurrent ependymoma
  • To correlate response, either by objective response or progression-free survival at 12 months with EGFR expression, PTEN expression and MGMT gene promoter methylation status.
  • Determine the efficacy of the combination of lapatinib and temozolomide in spinal cord ependymoma as a component of a pilot study.
  • To evaluate longitudinal changes in symptom measures and determine the impact of the therapy on these parameters.
  • To measure symptom burden over the course of therapy to evaluate differences between patients individual symptom severity, overall mean symptom severity, and difference in scores on the interference items between responders and non-responders.
  • To describe the variability of symptom severity longitudinally over the treatment course and follow-up period.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:12/12/2008
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:50
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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 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) 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: SGPT [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 MDACC OMCR database prior to treatment with study drug.

15) Women of childbearing potential must have a negative beta-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 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 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 CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with 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 IV alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease).

14) Patients cannot be receiving EIAEDs nor any other 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.

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Links
Registration Number: NCT00826241
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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