Dose-Dense Temozolomide + Lapatinib for Recurrent Ependymoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00826241
Recruitment Status : Unknown
Verified March 2015 by National Institutes of Health Clinical Center (CC).
Recruitment status was:  Active, not recruiting
First Posted : January 22, 2009
Last Update Posted : October 22, 2015
CERN Foundation - Collaborative Ependymoma Research Network
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC)

Brief 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.

Condition or disease Intervention/treatment Phase
Brain Tumors Spinal Cord Tumors Drug: Temozolomide Drug: Lapatinib Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma
Study Start Date : January 2009
Estimated Primary Completion Date : January 2017

Arm Intervention/treatment
Experimental: Temozolomide + Lapatinib
Temozolomide starting dose 125 mg/m2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth.
Drug: Temozolomide
Starting dose 125 mg/m2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle.
Other Name: Temodar

Drug: Lapatinib
Starting dose 1250 mg daily by mouth.
Other Name: GW572016

Primary Outcome Measures :
  1. Time to Progression [ Time Frame: Assessed every two months till disease progression ]
    Time to progression defined as progressive disease, toxicity at a level of severity that precludes the patient continuing on the protocol, or death.

Secondary Outcome Measures :
  1. Anti-Tumor Activity [ Time Frame: 4 weeks ]
    Anti-tumor activity determined by the overall response complete response of partial response (CR or PR) rate. MacDonald criteria used to determine overall response.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00826241

United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Institutes of Health Clinical Center (CC)
CERN Foundation - Collaborative Ependymoma Research Network
Principal Investigator: Marta Penas-Prado, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) Identifier: NCT00826241     History of Changes
Other Study ID Numbers: 999916005
NCI-2012-02131 ( Other Identifier: NCI )
16-C-N005 ( Other Identifier: NIH )
First Posted: January 22, 2009    Key Record Dates
Last Update Posted: October 22, 2015
Last Verified: March 2015

Keywords provided by National Institutes of Health Clinical Center (CC):
Brain Tumor
Central Nervous System
Spinal Cord Tumor
Anaplastic Ependymoma
Supratentorial Ependymoma
Infratentorial Ependymoma
Spinal Cord Ependymoma

Additional relevant MeSH terms:
Brain Neoplasms
Spinal Cord Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Spinal Cord Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors