Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Glioblastoma

Brain Neoplasms

Astrocytoma

Oligodendroglioma

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

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Anaplastic Oligoastrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Temozolomide

Motexafin gadolinium

Photosensitizing Agents

Motexafin Gadolinium Injection

The purpose of this study is to find out about the safety of adding the investigational drug motexafin gadolinium to a standard course of chemotherapy with temozolomide for patients with malignant glioma. Secondly, the study will determine how many patients will respond to this treatment.

A Study of Motexafin Gadolinium and Temozolomide for the Treatment of Malignant Gliomas

Phase I Trial of Motexafin Gadolinium (MGd) in Combination With Temozolomide for Treatment of Malignant Gliomas

Pharmacyclics LLC.

Symptoms and General Pathology

Recurrence

Gliosarcoma

Anticonvulsants

Patients who are not on enzyme inducing anti-epileptic drugs (EIAEDs) and are scheduled to undergo salvage surgical resection treated with preoperative AC480 at 300 mg BID followed by post-surgical AC480 at 300 mg BID.

Subjects will be initiated on AC480 300mg orally BID for 14 (+/-2 days) before surgery. After surgery, subjects will continue to be dosed with AC480 until either disease progression or intolerance, and will be evaluated every other cycle (i.e., every 4 weeks).

AC480

Annick Desjardins, MD, FRCPC

The primary objective is to evaluate the intratumoral and plasma pharmacokinetics of AC480 among patients who are candidates for a resection with a recurrent malignant glioma who are not on CYP-3A enzyme inducing anti-epileptic drugs (EIAEDS). Secondary objectives include the following: to evaluate the antiproliferative effect of AC480 by FDG-PET Scan; to evaluate the safety and tolerability of AC480; and, to describe 6-month progression-free survival (PFS) and radiographic response.

This is a single institution, open label, pharmacokinetic study of AC480 in patients with recurrent malignant glioma. The study will enroll 5 patients who are not on enzyme inducing anti-epileptic drugs (EIAEDs) and are scheduled to undergo salvage surgical resection for preoperative treatment with AC480 at 300 mg orally twice daily (BID) for 14 (plus or minus 2) days before surgery (Part I- Induction Therapy). After surgery (Part II- Maintenance Therapy), patients will continue to be dosed with AC480 until disease progression or intolerance, and will be evaluated after every other cycle (1 cycle is 28 days).

Plasma and tumoral pharmacokinetics, as well as FDG-PET data will be analyzed to determine the intratumoral and plasma levels of AC480 obtained and its antiproliferative activity. After recovery from surgery, all patients will resume AC480 at 300 mg orally BID until evidence of disease progression or toxicity (Part II: Maintenance Therapy). Those patients will be followed for determination of 6-month progression free survival. Patients will remain on treatment for as long as they have clinical benefit from the treatment. There will be no limit to the number of cycles of treatment a patient can receive providing they continue to benefit from and are not intolerant to AC480 administration.

The data collected in this study will be summarized in tables listing the mean, standard deviation, and number of patients for continuous data, or in tables listing count and percentage for categorical data, where appropriate. All patient data will be listed by patient or by parameter, all statistical analyses will be performed and all data appendices will be created by using the SAS system. Pharmacokinetic analysis will be made to determine if AC480 reaches the intracerebral tumor tissue. Comparisons will be made between the data obtained from the plasma of the same patients treated on AC480, including determination of the tumor-to-plasma ratio. The most common side effects of AC480 are generally mild to moderate in severity and include: nausea, vomiting, diarrhea, fatigue, cough, elevation of the liver enzymes, anemia, and rash.

Pharmacokinetics (PK) Study of AC480 for Recurrent Glioma

A Pharmacokinetic Study of AC480 Administered Twice Daily in Surgically Resectable Malignant Glioma Patients Not on Enzyme-Inducing Anticonvulsants

Ambit Biosciences Corporation

Annick Desjardins

Assist Professor of Medicine-Neurology

Meningioma

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Analgesics

Immunomodulating Agents

Interleukin-2

alloreactive CTL

The purpose of this research study to determine if treating recurrent malignant gliomas with another person's (donor) immune system cells known as aCTL cells, will be safe. This study will also try to determine if persons who receive aCTL's are more or less likely to survive their brain tumor than persons who had similar tumors in the past. Approximately 15 patients will be enrolled at UCLA.

Cellular Immunotherapy Study for Brain Cancer

A Phase I Clinical Trial Evaluating Cellular Immunotherapy With Intratumoral Alloreactive Cytotoxic T Lymphocytes and Interleukin-2 for the Treatment of Recurrent Malignant Gliomas or Meningiomas

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Jonsson Comprehensive Cancer Center

Channel Blockers

Central Nervous System Depressants

Psychotropic Drugs

Fosphenytoin

Dasatinib

Phenytoin

Carbamazepine

Phenobarbital

Oxcarbazepine

Primidone

Subjects taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs).

Subjects NOT taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs).

Subjects taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs Phenytoin/Dilantin, Fosphenytoin/Cerebyx, Phenobarbital, Primidone/Mysoline, Oxcarbazepine/Trileptal, Carbamazepine/Tegretol).

enzyme-inducing anti-epileptic drugs

Subjects NOT taking EIAEDs (CYP-3A enzyme-inducing anti-epileptic drugs Phenytoin/Dilantin, Fosphenytoin/Cerebyx, Phenobarbital, Primidone/Mysoline, Oxcarbazepine/Trileptal, Carbamazepine/Tegretol).

Annick Desjardins, MD

The primary objective of this study is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of dasatinib when combined with protracted, daily temozolomide (TMZ). Secondary objectives are: To further evaluate the safety and tolerability of dasatinib plus protracted, daily TMZ; 2. To evaluate the pharmacokinetics of dasatinib when administered with protracted, daily TMZ among recurrent malignant glioma patients who are on and not on CYP-3A enzyme inducing anti-epileptic drugs (EIAEDs); 3. To evaluate for anti-tumor activity with this regimen in this patient population.

This is an open-label, single center, one-arm phase I dose-escalation study of dasatinib plus protracted , daily TMZ administered orally on a continuous daily dosing schedule among adult patients with recurrent or relapsing malignant glioma. The study format includes a classical "3+3" dose escalation design to determine the MTD and DLT of dasatinib plus protracted, daily TMZ among recurrent malignant glioma patients. Patients will be stratified based on whether they are receiving EIAED and each stratum will independently dose escalate. Additionally, the study will characterize the safety, tolerability, biologic activity, and pharmacokinetic profile of dasatinib when used in combination with protracted, daily TMZ.

Patients will start treatment on day 1 of cycle 1 with dasatinib. For patients undergoing dasatinib pharmacokinetic (PK) analysis, dasatinib will be administered alone until initial PK assessments are collected. Protracted TMZ will be initiated after initial dasatinib PK assessments are collected and will continue to be administered with dasatinib on a continuous daily dosing schedule. The initial dasatinib PK assessments will be collected over 24 hours between days 3-7 of cycle 1. Patients not undergoing dasatinib PK collections will begin both dasatinib and protracted, daily TMZ together on day 1, cycle 1.

The protracted, daily TMZ dose will be 50 mg/m² daily for all patients. The dose level of dasatinib will be increased in successive cohorts. Cohorts of 3-6 patients will accrue at each dose level until MTD is defined. Each cohort will consist of a minimum of 3 newly enrolled patients. Intra-patient dose escalation is not permitted. It is estimated that this study will enroll a minimum of 30 patients (up to 4 dose levels/stratum; 3 patients/dose level for levels 1-3 and 6 patients at level 4) and a maximum of 48 patients (6 patients/dose level; 4 dose levels/stratum). Cohorts may be expanded at any dose level for further elaboration of safety and pharmacokinetic parameters as required.

The primary safety and efficacy analysis will be conducted on all patient data at the time all patients who are still receiving study drug will have completed at least 4 cycles of treatment. The additional data for any patients continuing to receive study drug past this time, as allowed by the protocol, will be further summarized in a report once these patients either completed or discontinued the study. Prior to the primary analysis, an additional safety report may be prepared.

The most common side effects include vomiting, diarrhea, anorexia (loss of appetite), fluid retention, fatigue, headache, rash, hypocalcemia (low calcium level), and decreases in blood counts. Other possible side effects may include nausea, joint pain, muscle aches, generalized pain, abdominal pain, and fever. Rare side effects may include QTc prolongation (heart beat changes), pulmonary edema (fluid around the lungs), difficulty breathing, cough, hemorrhage, gastrointestinal bleeding, pneumonia, cardiac effusion (fluid in the sac surrounding the heart), and cardiac failure. Temodar has been well tolerated by both adults and children with the most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea and vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, hepatotoxicity, anorexia, fatigue and hyperglycemia. As in the case with many anti-cancer drugs, Temodar may be carcinogenic. Rats given Temodar have developed breast cancer.

Ph. I Dasatinib/Protracted Temozolomide in Recurrent Malignant Glioma

Phase I Study of Dasatinib Plus Protracted Temozolomide in Recurrent Malignant Glioma

Bristol-Myers Squibb

Capecitabine

Antimetabolites

Capecitabine (1,000-1,250 mg/m2) taken by mouth twice daily for 14 out of 21 consecutive days until progression or unacceptable toxicity.

1,000-1,250 mg/m2 taken by mouth twice daily for 14 out of 21 consecutive days until progression or unacceptable toxicity.

Erin Dunbar, MD

The purpose of this study is to determine if capecitabine is effective in the treatment of high grade gliomas that have returned after completing treatment.

High grade gliomas (HGGs) represent a heterogenous group of primary brain tumors that share WHO grade III or IV classification (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma, and glioblastoma multiforme). Despite the upfront use of surgery, radiation, and chemotherapy, high grade gliomas uniformly result in recurrence and death. Palliative chemotherapy offers an improvement in time to progression, symptom control, quality of life, and potential survival; however, no established chemotherapy regimen for recurrence exists and new treatments are needed. Oral capecitabine is a rationale strategy for therapeutic palliation of recurrent high grade gliomas given its oral administration, its well-known kinetics and toxicities, its non-competitive toxicities to other high grade glioma treatments, its well established management algorithms, its established evidence of entry into the central nervous system, and its evidence of safety and efficacy in malignancies in the central nervous system.

Study of Capecitabine to Treat Recurrent High Grade Gliomas

Pilot Study to Determine Therapeutic Response of Oral Capecitabine (Xeloda) in Recurrent High Grade Gliomas (HGGs) by Establishing the Radiographic Response Rate Using Modified Macdonald Criteria

Gadolinium-contrasted MRIs were used to assess radiographic response every 2 cycles (\~6 weeks). Tumor progression was defined by increasing tumor size, new areas of tumor, or unequivocal neurologic deterioration.

University of Florida

Capecitabine (1,000-1,250 mg/m2) was taken by mouth twice daily for 14 out of 21 consecutive days until disease progression or unacceptable toxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Motexafin Gadolinium and Temozolomide for the Treatment of Malignant Gliomas	NCT00080054	Glioma Glioblastoma Astrocytoma Oligodendroglio... Brain Neoplasm	Motexafin Gadol...	18 Years -	Pharmacyclics LLC.
Pharmacokinetics (PK) Study of AC480 for Recurrent Glioma	NCT00979173	Glioma	AC480	18 Years -	Duke University
Cellular Immunotherapy Study for Brain Cancer	NCT01144247	Gliomas Anaplastic Astr... Anaplastic Olig... Anaplastic Mixe... Glioblastoma Mu... Malignant Menin...	alloreactive CT...	18 Years -	Jonsson Comprehensive Cancer Center
Cellular Immunotherapy Study for Brain Cancer	NCT01144247	Gliomas Anaplastic Astr... Anaplastic Olig... Anaplastic Mixe... Glioblastoma Mu... Malignant Menin...	alloreactive CT...	18 Years -	Jonsson Comprehensive Cancer Center
Ph. I Dasatinib/Protracted Temozolomide in Recurrent Malignant Glioma	NCT00734864	Glioblastoma Mu... Gliosarcoma Anaplastic Astr... Anaplastic Olig... Glioma	enzyme-inducing... enzyme-inducing...	18 Years -	Duke University
Ph. I Dasatinib/Protracted Temozolomide in Recurrent Malignant Glioma	NCT00734864	Glioblastoma Mu... Gliosarcoma Anaplastic Astr... Anaplastic Olig... Glioma	enzyme-inducing... enzyme-inducing...	18 Years -	Duke University
Study of Capecitabine to Treat Recurrent High Grade Gliomas	NCT00717197	Malignant Gliom...	Capecitabine	18 Years -	University of Florida
Pharmacokinetics (PK) Study of AC480 for Recurrent Glioma	NCT00979173	Glioma	AC480	18 Years -	Duke University
Ph. I Dasatinib/Protracted Temozolomide in Recurrent Malignant Glioma	NCT00734864	Glioblastoma Mu... Gliosarcoma Anaplastic Astr... Anaplastic Olig... Glioma	enzyme-inducing... enzyme-inducing...	18 Years -	Duke University

Spots Global Cancer Trial Database for anaplastic mixed glioma