Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Neuroepithelioma

All Drugs and Chemicals

Antibodies

Immunoglobulins

Mitogens

AMG 595

Immunoconjugates

Immunologic Factors

Pre-specified nominal doses are proposed in the dose exploration. Intermediate doses may also be used if required based on the CRM design.

Dose selected from Part 1 dose exploration

AMG 595 is an antibody drug conjugate that binds to EGFRvIII.

This is an open-label, sequential dose exploration study of single agent AMG 595 administered in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA). The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics (PK) of AMG 595, and also to evaluate the objective response rate in subjects receiving AMG 595. This study will be conducted in two parts. Part 1 will explore doses of AMG 595 in subjects with recurrent GBM and/or AA. Part 2 (dose expansion) will examine the MTD established in Part 1 in subjects with recurrent GBM.

This study of AMG 595 will be conducted in two parts: Part 1 (dose exploration) and Part 2 (dose expansion). Part 1 of the study is in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA), and Part 2 is examining the MTD in subjects with recurrent GBM. Approximately 30-40 subjects may be enrolled in Part 1, and up to 36 subjects may be enrolled in Part 2. The dose of AMG 595 utilized in Part 2 will be dependent upon data obtained in Part 1 of the study.

AMG 595 First-in-Human in Recurrent Gliomas

A Phase 1 First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 595 in Subjects With Recurrent Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)

Amgen

Ependymoma

Oligodendroglioma

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anaplastic Oligodendroglioma

Anaplastic Ependymoma

Photodynamic therapy using Photosan and LumaCare™ Lamp Model LC-122M

Jui-Chang Tsai, M.D. Ph.D.

Primary Objective:

* The primary objective is to evaluate the efficacy of photodynamic therapy in the treatment of malignant intracranial tumors.

Secondary Objective:

* The secondary objective is to evaluate the safety of photodynamic therapy in the treatment of malignant intracranial tumors.

After passing Photosan® allergic test, the patients will be injected intravenously with Photosan® (2mg/kg) during 15\~30 minutes, 48 hours prior to a standard craniotomy. Precautions are taken not to expose the patient in the operating room to direct room or operating light and to shield the skin of the flap during operation. Steroids are withdrawn 2-3 days prior to sensitization. After maximal resection, the surface of the tumor bed will be calculated and the generated cavity kept with a balloon containing intralipid (0.1%) or saline and/or artificial spinal fluid in it. A fiber with a spherical diffuser will be centered in the cavity and the surface irradiated with red (625\~635nm) Halogen light. The dose of light irradiation depends on individual condition of the patient, usually with an energy density of 100 J/cm2 at a power density of 500 mW/cm2 to 600 mW/cm2.

Photodynamic Therapy in the Treatment of Malignant Intracranial Tumors

Prospective, Open-labeled, Clinical Trial in Compassionate Use to Evaluate the Efficacy and Safety of Photodynamic Therapy in the Treatment of Malignant Intracranial Tumors

National Taiwan University Hospital

Antineoplastic Agents

Temozolomide

O(6)-benzylguanine

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Objectives of study are to define role of BG in restoring Temodar sensitivity in patients with Temodar-resistant malignant glioma and to further define the toxicity of combination therapy using Temodar + BG. 2 separate strata accrued independently of each other: Stratum 1-patients with glioblastoma multiforme (GBM). Stratum 2-patients with anaplastic glioma (AG).

BG at 120mg/m2 administered intravenously over 1 hour followed immediately by 48-hour infusion at 30mg/m2/24 hours. Temodar 472mg/m2 administered orally, in fasting state, within 60 minutes of end of the 1-hour administration of BG infusion. Treatment cycles may be repeated every 28 days following dose of Temodar from previous cycle.

Temodar and O6-Benzylguanine (BG)

David A. Reardon, MD

Objectives:

To define role of O6-Benzylguanine (BG) in restoring Temodar (temozolomide) sensitivity in patients with Temodar-resistant malignant glioma.

To further define toxicity of combo therapy using Temodar + BG.

2 separate strata accrued independently of each other: Stratum 1-patients with Glioblastoma Multiforme (GBM). Stratum 2-patients with Anaplastic Glioma \[anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed (AA and AO)\] .

BG at 120mg/m2 administered intravenously over 1 hour followed immediately by 48-hour infusion at 30mg/m2/24hrs. Temozolomide 472mg/m2 administered orally, in fasting state, within 60 minutes of end of the 1-hour administration of BG infusion. Treatment cycles may be repeated every 28 days following dose of Temodar from previous cycle.

Temodar has been well tolerated by both adults and children with 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. Hypersensitivity reactions have not yet been noted with Temodar. As in the case with many anti-cancer drugs, Temodar may be carcinogenic. BG toxicities include agitation, lethargy, nausea, vomiting, rapid heart rate, elevated liver functions, \& leukemia; but, not with BG as single agent. Transient lymphopenia has been seen with BG as single agent.

Ph. II Temozolomide + O6-BG in Treatment of Pts w Temozolomide-Resistant Malignant Glioma

Phase II Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Temodar-Resistant Malignant Glioma

Keryx / AOI Pharmaceuticals, Inc.

National Institutes of Health (NIH)

Duke University

Bevacizumab

Etirinotecan pegol

Lawrence Recht, MD

High Grade Gliomas, including anaplastic astrocytomas, anaplastic oligodendrogliomas and glioblastomas (GBM), are the most common and most aggressive primary brain tumors. Prognosis for patients with high-grade gliomas remains poor. The estimated median survival for patients with GBM is between 12 to 18 months. Recurrence after initial therapy with temozolomide and radiation is nearly universal. Since May 2009, the majority of patients in the US with an initial recurrence of high-grade glioma receive bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), which is thought to prevent angiogenesis in these highly vascular tumors. BEV has response rates from 32-62% and has improved overall median survival in patients with recurrent high-grade gliomas1. However, the response is short lived, and nearly 100% of patients eventually progress despite bevacizumab. No chemotherapeutic agent administered following progression through bevacizumab has made a significant impact on survival. Patients progress to death within 1-5 months after resistance develops. Therefore, patients with high-grade gliomas who have progressed through bevacizumab represent a population in dire need of a feasible and tolerable treatment.

NKTR-102 is a topoisomerase I inhibitor polymer conjugate that was engineered by attaching irinotecan molecules to a polyethylene glycol (PEG) polymer using a biodegradable linker. Irinotecan released from NKTR-102 following administration is further metabolized to the active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN38), that causes DNA damage through inhibition of topoisomerase. The goal in designing NKTR-102 was to attenuate or eliminate some of the limiting side effects of irinotecan while improving efficacy by modifying the distribution of the agent within the body. The size and structure of NKTR-102 results in marked alteration in pharmacokinetic (PK) profile for the SN38 derived from NKTR-102 compared to that following irinotecan: the maximal plasma concentration (Cmax) is reduced 5- to 10-fold and the half-life (t1/2 ) of SN38 is increased from 2 days to approximately 50 days. This altered profile leads to constant exposure of the tumor to the active drug. In addition, the large NKTR-102 molecule does not freely pass out of intact vasculature, which may account for relatively higher concentrations of the compound and the active metabolites in tumor tissues in in vivo models, where the local vasculature may be relatively more permeable. A 145 mg/m2 dose of NKTR-102, the dose intended for use in this phase II clinical trial (and being used in the phase III clinical program), results in approximately the same plasma exposure to SN38 as a 350 mg/m2 dose of irinotecan, but exposure is protracted, resulting in continuous exposure between dosing cycles and lower Cmax. NKTR-102 was therefore developed as a new chemotherapeutic agent that may improve the clinical outcomes of patients.

Phase II NKTR-102 In Bevacizumab-Resistant High Grade Glioma

A Phase II, Single Arm, Open Label Study Of NKTR-102 In Bevacizumab-Resistant High Grade Glioma

Will be described using Kaplan-Meier estimates. The PFS probability at 6 weeks (PFS-6week) will be estimated with an 80% power and 95% confidence intervals (80% in accord with the planned alpha level, 95% for comparability with other studies, confidence intervals based on the Greenwood formula for the variance of a survival probability).

Will be described using Kaplan-Meier estimates.

Nektar Therapeutics

Lawrence Recht

Professor of Neurology and Neurological Sciences

Drug: Etirinotecan Pegol

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Lawrence Recht, MD, Professor of Neurology

Progression Free Survival, Assessed by Revised Assessment in Neuro-oncology (RANO) Criteria

Survival From the Time of First NKTR-102 Dose for Patients With BEV-resistant Glioma Receiving NKTR-102 to Date of Death

Overall Survival From Time of Diagnosis

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Gland and Hormone Related Diseases

Musculoskeletal Diseases

Eye Diseases

Meningioma

Lymphoma

Pituitary Diseases

Germinoma

Pituitary Neoplasms

Craniopharyngioma

Adamantinoma

Chordoma

Optic Nerve Glioma

Disease Attributes

Lymphosarcoma

Germ Cells Tumors

Central Nervous System Germinoma

Primary Central Nervous System Lymphoma

Pilocytic Astrocytoma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Pharmaceutical Solutions

Dermatologic Agents

Central Nervous System Depressants

Immunomodulating Agents

Dihematoporphyrin Ether

Trioxsalen

Hematoporphyrin Derivative

Ether

Photosensitizing Agents

Photofrin photodynamic therapy. Drug - 2.5 mg/kg, light - 240 mJ/cm2.

The subjects will receive a dose of 2.5 mg/kg of Photofrin intravenously 24 hours before planned surgical resection. Tumor resection will be carried out in the standard fashion in order to achieve the maximum tumor resection compatible with preservation of neurological function. After resection, Intralipid will be infused into the craniotomy and kept for approximately 45 min, while PDT will be performed. The illumination time will be calculated from the power density (mW) emitted by the laser and the radius (r) of the cavity to deliver a total light dose of 240 J/cm2 at a using the following formula:

Treatment Time (sec) = Light dose (J/cm2) x Cavity surface (cm2) x 1000 Power density (mW) Cavity Surface (cm2) = 4 x 3.14 x r2 The optical fiber will be placed in the center of the surgical cavity and photoillumination will commence. After PDT, the Intralipid solution will be removed and the wound will be closed. The subject will be sent to the intensive care area for recovery.

Photofrin photodynamic therapy.

Harry T Whelan, MD

This study will be aimed at investigating the effectiveness of a treatment for brain tumors called Photodynamic Therapy, or PDT. Briefly, a subject will receive a light-sensitive drug, called Photofrin®, the day before a tumor removal surgery. The next day, after the tumor is removed, red light from a laser will be shone into the tumor cavity through a light-diffusing sphere. This light will activate the photosensitizer, and possibly kill any tumor cells that may be left.

We plan to measure how long the subject may go without a new tumor regrowth, and overall how long subjects survive. We will compare these results to typical results to see if we are seeing any improvements.

Objective: To define the antitumor activity of Photofrin® and laser light activation within the confines of a Phase II study.

Photodynamic therapy (PDT) is a well-known treatment for other type of tumors; however it is an experimental treatment for brain tumors. There is much we do not know about the effectiveness of PDT in patients with brain tumors. The purpose of this study is to define the antitumor activity of Photofrin® and laser light activation. Photofrin® is a photosensitizing drug (a dye that is activated by light) used in PDT. We want to test the activity of PDT and to see what are the effects (good and bad) on you and your brain tumor. We also want to learn if this treatment will cause brain tumors to shrink and whether it will help patients with brain tumors to live longer.

PDT is a cancer treatment that involves giving a photosensitive dye (Photofrin®), into your vein through a tube (called an IV). This dye will go inside of the cancer cells more than it will go inside the normal, healthy cells. PDT using Photofrin® is an approved treatment in patients with certain types of cancer such as lung, and esophageal (from the mouth to the stomach) cancers.

Everyone in this study will receive Photofrin® (porfimer sodium) for injection (Pinnacle Biologics, Inc., Bannockburn, IL, USA), and be treated with red light emitted by a red laser. The light will be sent from the laser to the surface of the brain where the tumor is located using a light transmitting fiber. The fiber will have a knob at the end that spreads the light out evenly in all directions.

Previous studies have shown that patients with malignant brain tumors called gliomas had a good response to PDT. The patients in these studies lived longer than they were expected to live. In one study of adults with brain tumors in Australia, patients given PDT had greatly improved survival rates. Fifty seven percent (57%) of the patients with gliomas called anaplastic astrocytoma survived for 36 months. Thirty seven percent (37%) of the patients with gliomas called glioblastoma multiforme survived for 36 months. Froedtert Hospital, in Milwaukee WI, has been involved in PDT studies in adults in the past. This current study is is being done in a very similar way to the study done in Australia, and will use increased Photofrin®) and light doses than our previous study.

Photodynamic Therapy (PDT) For Recurrent High Grade Gliomas

A Phase II Study of Photodynamic Therapy (PDT) With Photofrin® (IND 104,613) For Recurrent High Grade Gliomas in Adults

Relapse free survival is the proportion of subjects who have gone six months since PDT without the disease getting worse.

To obtain preliminary data toward determining whether this combination results in higher remission rate when compared to historical data.

To further explore and report progression-free survival and overall survival for three years post PDT treatment.

To measure complete response, partial response, stable disease or progressive disease using the response assessment for Neuro-Oncology (RANO) criteria with the follow-up medical imaging, which specifically incorporates volumetric measurements of brain tumor enhancement and clinical measures of neurological decline and to compare these outcomes to historical controls.

Pinnacle Biologics Inc.

Bleser Professor of Neurology

Photofrin photodynamic therapy. Drug - 2.5 mg/kg, light - 240 mJ/cm2.

Photofrin photodynamic therapy.: The subjects will receive a dose of 2.5 mg/kg of Photofrin intravenously 24 hours before planned surgical resection. Tumor resection will be carried out in the standard fashion in order to achieve the maximum tumor resection compatible with preservation of neurological function. After resection, Intralipid will be infused into the craniotomy and kept for approximately 45 min, while PDT will be performed. The illumination time will be calculated from the power density (mW) emitted by the laser and the radius (r) of the cavity to deliver a total light dose of 240 J/cm2 at a using the following formula:

Treatment Time (sec) = Light dose (J/cm2) x Cavity surface (cm2) x 1000 Power density (mW) Cavity Surface (cm2) = 4 x 3.14 x r2 The optical fiber will be placed in the center of the surgical cavity and photoillumination will commence.

Photofrin Photodynamic Therapy.

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Early termination with only one participant enrolled.

Dr. Harry T. Whelan

Six Month Relapse-free Survival (RFS).

Study closed before three year period was completed. Only one participant was enrolled.

Remission Rate.

Progression-free Survival and Overall Survival.

Participant lost to followup before secondary outcome was assessed.

Tumor Response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AMG 595 First-in-Human in Recurrent Gliomas	NCT01475006	Advanced Malign... Anaplastic Astr... Glioblastoma Mu...	AMG 595	18 Years -	Amgen
Photodynamic Therapy in the Treatment of Malignant Intracranial Tumors	NCT00243490	Malignant Intra... Glioblastoma Mu... Anaplastic Astr... Anaplastic Olig... Anaplastic Epen...	Photodynamic th...	20 Years - 75 Years	National Taiwan University Hospital
Ph. II Temozolomide + O6-BG in Treatment of Pts w Temozolomide-Resistant Malignant Glioma	NCT00613093	Glioblastoma Mu... Anaplastic Glio...	Temodar and O6-...	18 Years -	Duke University
AMG 595 First-in-Human in Recurrent Gliomas	NCT01475006	Advanced Malign... Anaplastic Astr... Glioblastoma Mu...	AMG 595	18 Years -	Amgen
Photodynamic Therapy in the Treatment of Malignant Intracranial Tumors	NCT00243490	Malignant Intra... Glioblastoma Mu... Anaplastic Astr... Anaplastic Olig... Anaplastic Epen...	Photodynamic th...	20 Years - 75 Years	National Taiwan University Hospital
Phase II NKTR-102 In Bevacizumab-Resistant High Grade Glioma	NCT01663012	Anaplastic Astr... Anaplastic Olig... Glioblastomas (...	Etirinotecan pe...	18 Years -	Stanford University
Photodynamic Therapy (PDT) For Recurrent High Grade Gliomas	NCT01966809	Brain Tumor, Re...	Photofrin photo...	18 Years -	Medical College of Wisconsin

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