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A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Brain Tumors, Spinal Cord Tumors

Thank you

Trial Information

A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma


The Study Drugs:

Temozolomide is designed to kill cancer cells by damaging DNA (the genetic material of
cells). This could cause the tumor cells to die.

Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking
proteins inside the cancer cell, called the Her2/neu receptor and the epidermal growth
factor receptor (EGFR).

Study Drug Administration:

If you are found to be eligible to take part in this study, every day, you will take
lapatinib by mouth once a day in the morning. You should take lapatinib 1 hour before or 1
hour after eating, with at least 1 cup (about 8 oz.) of water.

On Days 1-7 and 15-21 of each cycle, you will take temozolomide by mouth 1 time each day.
You will start to take a lower dose of temozolomide for the first 2 cycles, then take a
higher dose for Cycles 3 and beyond if you tolerate the treatment. It should be taken at
least 2 hours before and 2 hours after eating with 1 cup (about 8 oz.) of water.

You should swallow temozolomide and/or lapatinib whole, one right after the other, without
chewing either of the study drugs. If you vomit while taking temozolomide and lapatinib, you
cannot take more capsules before the next scheduled dose. You should report any missed
pills or trouble you have with taking the pills to your study doctor. Your study doctor
will give you a form (patient diary) to fill out to keep track of your treatment. You will
be asked to return your completed diary and pill bottles at each visit with your doctor.

Each study "cycle" is 28 days.

Study Visits:

Every 2 weeks, blood (about 2-3 teaspoons) will be drawn for routine tests and to check your
blood's ability to clot.

Every 8 weeks, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your vital signs.

- You will have a neurological exam.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you have experienced any
side effects.

- You will complete the quality of life questionnaire.

- You will have an MRI scan to check the status of the disease.

- You will have either a MUGA scan (if the doctor thinks it is needed) or an
echocardiogram.

Length of Study:

You will be on study treatment for up to 2 years. You will be taken off study treatment
early if the disease gets worse or you experience intolerable side effects.

After you are off study, you may be able to continue taking lapatinib for as long as the
doctor thinks it is in your best interest. Your doctor will discuss this with you.

End-of-Study Visit:

After you go off study treatment, you will have an end-of-study visit. At this visit, the
following tests and procedures will be performed:

- You will have a physical exam.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you have experienced any
side effects.

- You will have a neurological exam.

- Blood (about 3 teaspoons) will be drawn for routine tests and to check your blood's
ability to clot.

- You will complete the questionnaire.

- You will have an MRI scan to check the status of the disease.

- You will have either a MUGA scan (if the doctor thinks it is needed) or an
echocardiogram.

Long-Term Follow-up Visit:

If you go off treatment (having completed the maximum 24 months on study drug treatment) and
have stable disease or response, you will have an MRI scan to check the status of the
disease every 2 months for first year after you are off study, then every 3 months for the
second year, then every 4 months for the third year, and then every 6 months from then on.

If you continue taking lapatinib after you have completed up to 24 months on study
treatment, you will have a clinic visit and an MRI scan to check the status of the disease
every 2 months for as long as the doctor thinks it is needed. At the clinic visits, you
will be asked how you are doing.

If you went off study treatment because the disease got worse or you experienced intolerable
side effects, after the end-of-study visit, the study staff will call you every 3 months
from then on to check how you are doing. Each phone call will take about 5 minutes.

This is an investigational study. Temozolomide is FDA approved or commercially available
for the treatment of tumors of the nervous system. Lapatinib is FDA approved and
commercially available for the treatment of breast cancer. However, lapatinib is not FDA
approved for the treatment of brain tumors. The use of lapatinib with temozolomide in the
treatment of brain tumors and spinal tumors is investigational.

Up to 50 patients will take part in this multicenter study. Up to 30 will be enrolled at MD
Anderson.


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
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.

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to Progression

Outcome Time Frame:

Assessed every two months till disease progression

Safety Issue:

Yes

Principal Investigator

Mark R Gilbert, MD, BS

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

CERN08-02

NCT ID:

NCT00826241

Start Date:

January 2009

Completion Date:

Related Keywords:

  • Brain Tumors
  • Spinal Cord Tumors
  • Brain Tumor
  • Central Nervous System
  • CNS
  • Spinal Cord Tumor
  • Anaplastic Ependymoma
  • Supratentorial Ependymoma
  • Infratentorial Ependymoma
  • Spinal Cord Ependymoma
  • Lapatinib
  • GW572016
  • Temozolomide
  • Temodar
  • Brain Neoplasms
  • Ependymoma
  • Spinal Cord Neoplasms

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021
University of California, San FranciscoSan Francisco, California  94143
Dana Farber Cancer InstituteBoston, Massachusetts  02115
UT MD Anderson Cancer CenterHouston, Texas  77030
University of Wisconsin School of Medicine and Public HealthMadison, Wisconsin  53792-5666
University of Pittsburgh Medical Center - Hillman Cancer CenterPittsburgh, Pennsylvania  15232