Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Neoplasm Metastasis

Seizures

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Neoplasms

Neurologic Manifestations

Brain Diseases

Central Nervous System Diseases

Anticonvulsants

Nootropic Agents

All Drugs and Chemicals

Levetiracetam

levetiracetam

quality-of-life assessment

Jeffrey J. Raizer, MD

RATIONALE: Anticonvulsant drugs, such as levetiracetam, may help control seizures caused by brain metastases.

PURPOSE: This clinical trial is studying the side effects and how well levetiracetam works in treating patients with seizures caused by brain metastases.

OBJECTIVES:

* Determine the optimal dose of levetiracetam required to control seizures from brain metastases in patients with solid tumors.
* Determine the frequency of side effects and tolerability of this drug when used to control seizures in these patients.
* Determine any improvement in antiepileptic drug-associated symptoms in these patients.

OUTLINE: This is a pilot study. Patients are stratified according to baseline seizures (yes vs no) and/or baseline antiepileptic drugs (AEDs) (yes vs no). Patients are assigned to 1 of 3 treatment groups.

* Group I (patients with no active baseline seizures): Patients receive oral levetiracetam twice daily beginning on day 1.
* Group II (patients requiring IV AEDs for baseline seizure control): Patients receive oral levetiracetam (instead of their current anticonvulsant therapy) twice daily beginning on day 1, after their presenting condition has stabilized.
* Group III (patients with active seizures controlled by other concurrent anticonvulsant monotherapy): Patients receive oral levetiracetam (instead of their current anticonvulsant therapy) twice daily beginning on day 1. Treatment with the other anticonvulsant drug is tapered beginning on day 3 as directed by the treating physician.

In all groups, treatment continues for up to 6 months in the absence of uncontrolled seizures or unacceptable toxicities.

During study therapy, patients maintain a seizure log that tracks frequency and type of seizures. Any patient who experiences a breakthrough seizure or multiple auras receives increasing doses of oral levetiracetam until the maximum dose is reached. Patients who continue to have seizures at the maximum dose level receive a second antiseizure medication at the discretion of the treating physician.

Quality of life is assessed by the Fundamental Assessment of Cancer Treatment-Brain questionnaire at baseline and at 2 months.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Levetiracetam in Treating Patients With Seizures Caused by Brain Metastases

A Pilot Study of the Efficacy of Levetiracetam in Patients With Seizures From Brain Metastases

National Cancer Institute (NCI)

Northwestern University

Musculoskeletal Diseases

Rare Diseases

Glioma

Glioblastoma

Astrocytoma

Meningioma

Oligodendroglioma

Medulloblastoma

Pinealoma

Ependymoma

Craniopharyngioma

Adamantinoma

Gliosarcoma

Solitary Fibrous Tumors

Hemangiopericytoma

Choroid Plexus Neoplasms

Glioma, Subependymal

Germ Cells Tumors

Pineocytoma

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Pineoblastoma

Pilocytic Astrocytoma

Anaplastic Ependymoma

Embryonal Tumor With Multilayered Rosettes

Subependymoma

Myxopapillary Ependymoma

Herbal and Botanical

Donepezil

Cholinesterase Inhibitors

Enzyme Inhibitors

Cholinergic Agents

Neurotransmitter Agents

Ginkgo

EGb761

donepezil hydrochloride

cognitive assessment

Edward G. Shaw, MD

RATIONALE: Donepezil and EGb761 may be effective in improving neurocognitive function (such as thinking, attention, concentration, and memory) and may improve quality of life in patients who have undergone radiation therapy to the brain.

PURPOSE: This phase II trial is studying how well donepezil or EGb761 works in improving neurocognitive function in patients who have undergone radiation therapy for primary brain tumor or brain metastases.

OBJECTIVES:

Primary

* Determine the effect of donepezil or EGb761 on neurocognitive function in patients who underwent radiotherapy for a primary brain tumor or brain metastases at least 6 months before study registration.

Secondary

* Determine the toxicity of these drugs in these patients.
* Determine the quality of life of patients treated with these drugs.
* Quantify the extent of radiation-induced white matter disease and temporal lobe atrophy in patients treated with these drugs.

OUTLINE: This is an open-label, multicenter study.

* Group 1 (closed to accrual 10/09/03): Patients receive oral donepezil once daily for 24 weeks.
* Group 2: Patients receive oral EGb761 three times daily for 24 weeks. In both groups (group 1 closed to accrual 10/09/03), treatment continues in the absence of unacceptable toxicity.

In both groups (group 1 closed to accrual 10/09/03), quality of life and neurocognitive assessment is performed at baseline and at weeks 6 (group 1 only), 12, 24, and 30.

Patients are followed at 6 weeks.

PROJECTED ACCRUAL: A total of 70 patients (35 per treatment group) will be accrued for this study within 9.5 months. (Group 1 closed to accrual 10/09/03)

Phase II Studies Of Donepezil And Ginkgo Biloba In Irradiated Brain Tumor

Donepezil and EGb761 in Improving Neurocognitive Function in Patients Who Have Previously Undergone Radiation Therapy for Primary Brain Tumor or Brain Metastases

Wake Forest University Health Sciences

Respiratory Tract (Lung and Bronchial) Diseases

Small Cell Lung Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

cilengitide

pharmacological study

radiation therapy

Christian Manegold, MD

RATIONALE: Cilengitide may stop the growth of brain metastases by blocking blood flow to the tumor. Radiation therapy uses high energy X-rays to kill tumor cells. Giving cilengitide together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of cilengitide when given together with whole-brain radiation therapy in treating patients with brain metastases from lung cancer.

OBJECTIVES:

* Primary

  * To assess the safety and tolerability of daily cilengitide by determining its dose-limiting toxicity and maximum-tolerated dose when combined with concomitant fractionated whole-brain radiation therapy in patients with brain metastases from lung cancer.
* Secondary

  * To collect evidence of the best overall response rate, overall survival, brain-specific progression-free survival, and tumor-specific progression-free survival of these patients.
  * To collect evidence of changes in functional MRI imaging studies at 6 and 12 weeks after initiation of therapy.
  * To collect evidence of early response by functional MRI (ASL technique) on days 1, 4, and 12, immediately before and after the administration of cilengitide.
  * To collect evidence of changes in neurological and neurocognitive function tests at 6 and 12 weeks after initiation of therapy.
  * To further evaluate the safety and toxicity of the combination of cilengitide and whole-brain radiation therapy.
  * To further evaluate the pharmacokinetics of cilengitide administered daily.

OUTLINE:

Patients receive oral cilengitide once daily and undergo whole-brain radiotherapy on the same days. Treatment continues for 2 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection on days 1, 4, 5, and 12 for pharmacokinetic studies.

After completion of study treatment, patients are followed for 10 weeks.

Cilengitide and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases From Lung Cancer

Cilengitide (EMD121974) in Combination With Whole Brain Radiotherapy in Patients With Brain Metastases From Lung Cancer - a Single-center, Open-label Phase I Study

(i) Any grade III-IV non-hematological toxicity as defined by CTCAE, version 3.0, with the exclusion ofalopecia, nausea, vomiting, and fever that can be rapidly contolled with appropriate measures; (ii) absolute neutrophil count (ANC)\<0.5x10'/L lasting for \>7days; (iii) febrile neutropenia defined as ANC \<1.0x10'/L and fever \>38.5°C; (iv) platelets \<25x10'/L or thrombocytopenic bleeding requiring transfusion; and (v) severe hypotension requiring dopamine administration.

5 planned steps to be tested: 100, 250, 500, 750, to 1000mg; the highest dose at which one or no DLT will have been observed among 6 patients

Every recurrence within the brain or death is an event, Kaplan-Meier (KM)

Every tumor related event or death will be counted, Kaplan-Meier (KM)

blood volume changes during functional MRI

(ASL technique) on day 1,4 and 12, immediately before and after the administration of cilengitide.

Intelligence was measured with a multiple-choice test of vocabulary knowledge.

Memory was tested by aims of "Medical College of Georgia Complex Figures"

Memory was tested by aims of "Rea Auditory Verbal Learning Test - German Version"

Perception was assessed by the "Digit Symbol Substitution Test"

Attention was tested by "Divided Attention"

"Functional Assessment of Cancer Therapy - Fatigue Subscale" measured in points (range 0-52)

"Hospital Anxiety and Depression Scale - German Version"

"Barthel Activities of Daily Living Index" measured in points (range 0-100)

"lnstrumental Activities of Daily Living Scale" measured in points (range 0-8)

Heidelberg University

Universitätsmedizin Mannheim

Prof. Christian Manegold

Carcinoma

Tetrahydrouridine

Antimetabolites

The study's starting dose of CldC is 50 mg/m2/day. The dose of CldC will be escalated / de-escalated for patients. Patients will receive CldC+H4U on 3 days (Wed, Thr, Fri) in week 1, which precedes the initiation of radiation therapy. Patients will receive H4U and CldC IV by bolus infusion. Treatment with CldC+H4U will then continue for 5 days (Mon-Fri) during each of weeks 2 and 3, and will be accompanied by radiation therapy at 3 Gy/fraction initiated 3-4 h after bolus infusion of CldC+H4U. Treatment with CldC+H4U and radiation will then stop at the end of week 3.

Cytochlor

A fixed dose of H4U at 720 mg/m2/day will be used, regardless of the dose of CldC administered. H4U will be delivered by an IV bolus infusion over a period of 5 minutes, followed 5 minutes later by an IV bolus infusion of CldC. Patients will receive CldC+H4U on 3 days (Wed, Thr, Fri) in week 1, which precedes the initiation of radiation therapy. Patients will receive H4U and CldC IV by bolus infusion. Treatment with CldC+H4U will then continue for 5 days (Mon-Fri) during each of weeks 2 and 3, and will be accompanied by radiation therapy at 3 Gy/fraction initiated 3-4 h after bolus infusion of CldC+H4U. Treatment with CldC+H4U and radiation will then stop at the end of week 3.

One treatment of 3 Gy will be given daily 5 days per week (10 fractions) for a total of 30 Gy over two weeks.

Radiation Therapy

Fazilat Ishkanian, MD

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as cytochlor and tetrahydrouridine, may make tumor cells more sensitive to radiation therapy.

PURPOSE: This phase I trial is studying the side effects and best dose of cytochlor when given together with tetrahydrouridine and external-beam radiation therapy in treating patients with cancer that has spread to the brain.

OBJECTIVES:

Primary

* Establish the safety and toxicity profile of cytochlor and H4U when given in combination with external-beam radiotherapy for 2 weeks after treatment with the drugs alone in the previous week.

Secondary

* Determine the effectiveness of H4U to inhibit systemic cytidine deaminase (CD) during the course of treatment with cytochlor and H4U.
* Perform detailed pharmacokinetic studies to determine the levels of cytochlor and its metabolites in serum and in urine in weeks 1, 2, and 3 during treatment.

OUTLINE: This is a dose-escalation study of cytochlor.

Patients receive cytochlor IV and tetrahydrouridine (H4U) IV over 5 minutes on 3 days in week 1 and on days 1-5 in weeks 2 and 3. Patients also undergo external-beam radiotherapy 5 days a week in weeks 2 and 3 initiated 3-4 hours after infusions of cytochlor and H4U. Treatment may repeat in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed monthly for 3 months, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then yearly thereafter.

Cytochlor, Tetrahydrouridine, and External-Beam Radiation Therapy in Treating Patients With Cancer That Has Spread to the Brain

Translational Phase I Trial of Escalating Doses of 5-Chloro-2'-Deoxycytidine (CldC) With a Fixed Dose of Tetrahydrouridine Combined With External Brain Radiation for Metastatic Carcinoma to the Brain

Baseline Levels of CD will be obtained by assaying CD in serum prior to initiation of treatment on Wednesday of week 1. Follow-up assays of CD in serum will be made on the Fridays of weeks 1 to 3 after each day's treatment with CldC + H4U. In weeks 2 and 3 this will take place prior to RT

Brian Lally

Assistant Professor of Clinical

Anti-Infective Agents

Antineoplastic Agents

Thalidomide

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Angiogenesis Inhibitors

Growth Inhibitors

temozolomide

thalidomide

Volker W. Stieber, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining whole-brain radiation therapy with thalidomide and temozolomide may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining whole-brain radiation therapy with thalidomide and temozolomide in treating patients who have newly diagnosed brain metastases.

OBJECTIVES:

* Determine the overall median survival time of patients with newly diagnosed brain metastases treated with whole-brain radiotherapy in combination with thalidomide and temozolomide.
* Determine the radiographic response rate, median time to tumor progression, and median time to neurologic response and progression in patients treated with this regimen.
* Determine the cause of death of patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.
* Assess quality of life of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients undergo radiotherapy daily 5 days a week for 3 weeks. Beginning on the day before the first radiation treatment, patients receive oral thalidomide once daily and oral temozolomide once daily for 21 days. Patients continue to receive thalidomide daily for up to 2 years in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 1 and 3 months after completing radiotherapy, and then every 3 months thereafter.

Patients are followed at 1 and 3 months and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study within 10 months.

Radiation Therapy Plus Thalidomide and Temozolomide in Treating Patients With Newly Diagnosed Brain Metastases

A Phase II Study Of Whole-Brain Radiation Therapy With Thalidomide And Temozolomide In Patients With Newly Diagnosed Brain Metastases

Henry S. Friedman, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have brain metastases.

OBJECTIVES:

* Determine the activity of temozolomide in patients with brain metastases.
* Determine the toxicity of this treatment in these patients.

OUTLINE: Patients are stratified according to type of primary cancer (lung carcinoma vs breast carcinoma vs malignant melanoma vs renal cell carcinoma vs colorectal carcinoma vs other).

Patients receive oral temozolomide daily on days 1-7 and 15-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 180 patients (30 per stratum) will be accrued for this study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Levetiracetam in Treating Patients With Seizures Caused by Brain Metastases	NCT00415376	Brain and Centr... Seizure Unspecified Adu...	levetiracetam quality-of-life...	18 Years -	Northwestern University
Phase II Studies Of Donepezil And Ginkgo Biloba In Irradiated Brain Tumor	NCT00070161	Brain and Centr... Radiation Toxic...	EGb761 donepezil hydro... cognitive asses...	18 Years - 120 Years	Wake Forest University Health Sciences
Cilengitide and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases From Lung Cancer	NCT00884598	Brain and Centr... Lung Cancer	cilengitide pharmacological... radiation thera...	18 Years -	Universitätsmedizin Mannheim
Cytochlor, Tetrahydrouridine, and External-Beam Radiation Therapy in Treating Patients With Cancer That Has Spread to the Brain	NCT00521183	Brain and Centr...	Cytochlor Tetrahydrouridi... Radiation Thera...	21 Years -	University of Miami
Radiation Therapy Plus Thalidomide and Temozolomide in Treating Patients With Newly Diagnosed Brain Metastases	NCT00049361	Brain and Centr... Unspecified Adu...	temozolomide thalidomide radiation thera...	18 Years - 120 Years	Wake Forest University Health Sciences
Radiation Therapy Plus Thalidomide and Temozolomide in Treating Patients With Newly Diagnosed Brain Metastases	NCT00049361	Brain and Centr... Unspecified Adu...	temozolomide thalidomide radiation thera...	18 Years - 120 Years	Wake Forest University Health Sciences
Temozolomide in Treating Patients With Brain Metastases	NCT00005954	Brain and Centr...	temozolomide	18 Years -	Duke University

Spots Global Cancer Trial Database for adult tumors metastatic to brain