Dose-Dense Temozolomide + Lapatinib for Recurrent Ependymoma

Study Description

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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 Design

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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

Arms and Interventions

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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

Outcome Measures

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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.

Eligibility Criteria

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

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 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.

Contacts and Locations

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Locations

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

Investigators

Principal Investigator:	Marta Penas-Prado, MD	M.D. Anderson Cancer Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

The University of Texas M.D.Anderson Cancer Center 

Responsible Party:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov 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
Last Update Posted:	October 22, 2015
Last Verified:	March 2015

Keywords provided by National Institutes of Health Clinical Center (CC):

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

Additional relevant MeSH terms:

Neoplasms; Brain Neoplasms; Spinal Cord Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Spinal Cord Diseases	Ependymoma; Central Nervous System Diseases; Nervous System Diseases; Glioma; Temozolomide; Dacarbazine; Lapatinib; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors