Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Brain Neoplasms

Ependymoma

Glioma, Subependymal

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Embryonal Tumor With Multilayered Rosettes

Subependymoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Bevacizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Lapatinib

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Bevacizumab 10 mg/kg given by vein over 90 minutes for first injection (30-60 minutes for subsequent doses) every 2 weeks while on study (2 times during each 4-week "study cycle"). Lapatinib Pills of 700 mg/m\^2/dose given orally 2 times each day.

10 mg/kg given by vein over 90 minutes for first injection (30-60 minutes for subsequent doses) every 2 weeks while on study (2 times during each 4-week "study cycle").

Pills of 700 mg/m\^2/dose given orally 2 times each day.

Michael E. Rytting, MD

The goal of this clinical research study is to learn if the combination of Avastin (bevacizumab) and Tykerb (lapatinib) can help to control ependymoma in pediatric patients. The safety of this drug combination will also be studied.

The Study Drugs:

Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent and/or slow down the growth of cancer cells.

Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive bevacizumab every 2 weeks while you are on study (2 times during each 4-week "study cycle"). The first time you receive the drug, it will be given by vein over 90 minutes. If this dose is well tolerated, you may receive future doses over 30 minutes.

You will take pills of lapatinib 2 times each day while you are on study. The pills should be taken at about the same time each day. You should not eat or drink anything except water for 1 hour before or 1 hour after you take the pills. If you miss a dose, do not take extra pills the next day to try and make up for the missed dose. You should report any missed pills or any trouble you may have with taking the pills to your study doctor.

You will be given a patient diary in which you must record what time you take lapatinib each time.

Study Visits:

At all study visits, you will be asked about any other drugs that you may be taking and about any side effects that you may be experiencing.

During Cycle 1 the following tests and procedures will be performed at least 1 time each week:

* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded.

Two (2) times each week during Cycle 1, blood (about 2-3 teaspoons) will be drawn for routine tests.

At the end of Cycle 1, urine will be collected for routine tests.

On Days 1 and 15 of Cycle 2, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded.
* Blood (about 2-3 teaspoons) will be drawn for routine tests.

At the end of Cycle 2, you will have an MRI scan of your head to check the status of the disease. If your doctor thinks it is needed, you will also have an MRI of your spine and a spinal tap to check your cerebrospinal fluid (CSF) for presence of disease.

On Day 1 of Cycle 3 and beyond, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded.
* Blood (about 2-3 teaspoons) and urine will be collected for routine tests.

Every 8 weeks, starting with the end of Cycle 4, while you are on study, the following tests and procedures will be performed:

* You will have an MRI scan of the brain to check the status of the disease.
* If your doctor thinks it is needed, you will have an MRI scan of the spine to check the status of the disease.
* If your doctor thinks it is needed, you will have a spinal tap to check your CSF for the presence of disease.

Every 12 weeks while you are on study, the following tests and procedures will be performed to check for possible side effects:

* You will have an echocardiogram or a multiple gated acquisition scan (MUGA) (if the study doctor thinks it is necessary) to test your heart function.
* You will have an x-ray of your right knee.
* If your doctor thinks it is needed, you will have an MRI scan of both knees.

Length of Study:

You will be on study for up to 2 years. You will be taken off study if the disease gets worse, if you experience intolerable side effects, or if the doctor thinks it is in your best interest.

End-of-Treatment Visit:

After you have finished receiving the study drugs, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* You will be asked about any other drugs that you may be taking and about any side effects that you may be experiencing.
* Your performance status will be recorded.
* Blood (about 2-3 teaspoons) will be collected for routine tests.
* You will have an echocardiogram or a MUGA scan (if the study doctor thinks it is necessary) to test your heart function.
* You will have an x-ray of your right knee.
* You will have MRI scans of the brain and spine to check the status of the disease.
* If your doctor thinks it is needed, you will have a spinal tap to check the status of the disease.

Long-Term Follow-up:

You will have a follow-up visit 30 days after you have finished receiving the study drugs. The following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* You will be asked about any other drugs that you may be taking and about any side effects that you may be experiencing.
* Your performance status will be recorded.
* Blood (about 2-3 teaspoons) will be collected for routine tests.

This is an investigational study. Bevacizumab is FDA approved and commercially available for the treatment of colon, rectum, lung and certain types of breast cancer. Lapatinib is FDA approved and commercially available for the treatment of certain types of breast cancer. The use of this drug combination in ependymomas in pediatric patients is investigational.

Up to 40 patients will take part in this multicenter study. Up to 6 patients will be enrolled at MD Anderson.

Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma

A Phase II Study of Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma

Objective response rate defined as number of participants out of total participants with complete response plus partial response (CR+PR) sustained for at least four weeks. Complete Response (CR) - Complete disappearance on magnetic resonance imaging (MRI) of all enhancing tumor and mass effect, on a stable or decreasing dose of corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination and must be sustained for at least 4 weeks. If cerebrospinal fluid (CSF) for presence of disease was positive it must become negative. Partial Response (PR) - Greater than or equal to 50% reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of corticosteroids, accompanied by stable or improving neurological examination and must be sustained for at least 4 weeks.

CERN Foundation - Collaborative Ependymoma Research Network

M.D. Anderson Cancer Center

Bevacizumab 10 mg/kg intravenous over 90 minutes for first injection (30-60 minutes for subsequent doses) every 2 weeks while on study (2 times during each 4-week "study cycle"). Lapatinib 700 mg/m\^2/dose given orally 2 times each day.

Bevacizumab + Lapatinib

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

MD Anderson Multicenter coordinating for Collaborative Ependymoma Research Network Study (CERN)

Of the total, 22 participants were eligible and only 20 evaluable for response.

Objective Response Rate

Overall Study

Skin and Connective Tissue Diseases

Glioblastoma

Meningioma

Astrocytoma

Oligodendroglioma

Gliosarcoma

Solitary Fibrous Tumors

Hemangiopericytoma

Neoplasms, Fibrous Tissue

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Brain Tumor, Adult

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Anaplastic Ependymoma

Anti-Infective Agents

Analgesics

Aldesleukin

Immunomodulating Agents

Glucocorticoids

Interleukin-2

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Patients receive intratumoral GRm13Z40-2 therapeutic allogeneic lymphocytes over 10 minutes on days 1 and 3 and intratumoral aldesleukin over 3 hours on days 2-5 (days 1-5 in week 2). Treatment repeats every week for 2 courses in the absence of disease progression or unacceptable toxicity.

therapeutic allogeneic lymphocytes

aldesleukin

laboratory biomarker analysis

positron emission tomography

Behnam Badie

RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Donor T cells that are treated in the laboratory may be effective treatment for malignant glioma. Aldesleukin may stimulate the white blood cells to kill tumor cells. Combining different types of biological therapies may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best way to give therapeutic donor lymphocytes together with aldesleukin in treating patients with stage III or stage IV malignant glioma.

PRIMARY OBJECTIVES:

I. To assess the safety of GRm13Z40-2 CTL CNS loco-regional cellular immunotherapy in research participants with recurrent or refractory/ progressive malignant glioma (WHO Grades 3 or 4).

II. To assess the safety of convection enhanced delivery (CED) of recombinant human Interleukin-2 (rhuIL-2) used in conjunction with GRm13Z40-2 CTL adoptive transfer.

SECONDARY OBJECTIVES:

I. To investigate the ability of 9-(4-fluoro-3-hydroxy-methyl-butyl) guanine (18FHBG) positron emission tomography PET to image GRm13Z40-2 CTL's in research participants.

II. To study the impact of concurrent dexamethasone administration on the tempo and magnitude of T cell allograft rejection responses in treated research participants by tracking the frequency of anti-GRm13Z40-2 immune responses in serially acquired peripheral blood samples.

III. To evaluate ganciclovir administration for ablating transferred GRm13Z40-2 in vivo should significant graft-mediated toxicities be encountered.

OUTLINE: Patients receive GRm13Z40-2 therapeutic allogeneic lymphocytes intratumorally (IT) over 10 minutes on days 1 and 3 and aldesleukin IT over 3 hours on days 2-5 (days 1-5 in week 2). Treatment repeats every week for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually for at least 15 years.

Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

City of Hope Medical Center

Medulloblastoma

Neuroblastoma

Rhabdoid Tumor

Neuroectodermal Tumors, Primitive, Peripheral

Eflornithine

Antiprotozoal Agents

Antiparasitic Agents

Ornithine

In this study subjects without CNS disease will receive oral difluoromethylornithine (DFMO) at a dose of 500 to 1000 mg/m2 BID

Subjects with CNS disease will receive a dose of 2500 mg/m2/dose BID in order to facilitate crossing into the CNS.

eflornithine HCl

Genevieve Bergendahl, MSN

Suzanne Treadway

Valerie Brown, MD

Giselle Sholler, MD

To provide DFMO in an expanded use setting to subjects with relapsed rare tumors with increased LIN28 expression or MYCN amplification or up regulation of ornithine decarboxylase.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma	NCT00883688	Brain Cancer Pediatric Cance...	Bevacizumab Lapatinib	- 21 Years	M.D. Anderson Cancer Center
Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2	NCT01082926	Anaplastic Astr... Anaplastic Epen... Anaplastic Meni... Anaplastic Olig... Brain Stem Glio... Ependymoblastom... Giant Cell Glio... Glioblastoma Gliosarcoma Grade III Menin... Meningeal Heman... Mixed Glioma Pineal Gland As... Brain Tumor	therapeutic all... aldesleukin laboratory biom... positron emissi...	18 Years - 70 Years	City of Hope Medical Center
An Intermediate Expanded Use Trial of DFMO	NCT03581240	Neuroblastoma Medulloblastoma Typical Teratoi... Embryonal Tumor... Ependymoblastom... Medulloepitheli...	eflornithine HC...	0 Years - 30 Years	Milton S. Hershey Medical Center
An Intermediate Expanded Use Trial of DFMO	NCT03581240	Neuroblastoma Medulloblastoma Typical Teratoi... Embryonal Tumor... Ependymoblastom... Medulloepitheli...	eflornithine HC...	0 Years - 30 Years	Milton S. Hershey Medical Center

Spots Global Cancer Trial Database for ependymoblastoma