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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 : Completed
First Posted : January 22, 2009
Results First Posted : March 22, 2019
Last Update Posted : March 22, 2019
CERN Foundation - Collaborative Ependymoma Research Network
Information provided by (Responsible Party):
Mark Gilbert, M.D., 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: N/A
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
Actual Study Start Date : January 2009
Actual Primary Completion Date : July 31, 2018
Actual Study Completion Date : July 31, 2018

Arm Intervention/treatment
Experimental: Temozolomide + Lapatinib
Temozolomide starting dose 125 mg/m^2 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/m^2 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, up to 4 years ]
    Time to progression defined as progressive disease, toxicity at a level of severity that precludes the patient continuing on the protocol, or death. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Secondary Outcome Measures :
  1. Number of Participants With an Overall Response (Complete Response or Partial Response) Assessed by the MacDonald Criteria [ Time Frame: 4 weeks ]
    Anti-tumor activity as determined by the overall response (Complete response (CR) or partial response (PR)) was assessed by the MacDonald criteria. Complete response is complete resolution of all lesions. The patient cannot be on any corticosteroids with the exception of adrenal replacement doses. Partial response is ≥50% reduction in the sum of products of all measurable lesions over baseline sum observed using the same techniques as baseline. The patient must be on a stable or decreased dose of corticosteroids to be evaluable for response.

  2. Number of Participants With Serious and Non-Serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) [ Time Frame: Date treatment consent signed to date off study, approximately 111 months and 26 days ]
    Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

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.

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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 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.

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

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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
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Principal Investigator: Marta Penas-Prado, MD M.D. Anderson Cancer Center
  Study Documents (Full-Text)

Documents provided by Mark Gilbert, M.D., National Institutes of Health Clinical Center (CC):
Informed Consent Form  [PDF] July 21, 2017

Additional Information:
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Responsible Party: Mark Gilbert, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC) Identifier: NCT00826241    
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
Results First Posted: March 22, 2019
Last Update Posted: March 22, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mark Gilbert, M.D., 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:
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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