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Infections

Rare Diseases

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Glioblastoma

Glioma

Brain Neoplasms

Virus Diseases

Astrocytoma

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Disease Attributes

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

Antineoplastic Agents

Immunomodulating Agents

Interleukin-12

single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

A single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

M032 (NSC 733972)

James M. Markert, MD

To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simplex Virus-1 in patients who would not be eligible for surgical resection of recurrent glioma To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simples Virus-1 in patients who would benefit from surgical resection of recurrent glioma

M032 is a second-generation oncolytic herpes simplex virus (oHSV) that is conditionally replication competent; that is, similar to G207, a first generation oHSV, it can replicate in tumor cells, but not in normal cells, thus killing the tumor cells directly through this process. Replication of M032 in the tumor itself not only kills the infected tumor cells, but causes the tumor cell to act as a factory to produce new virus. These virus particles are released as the tumor cell dies, and can then proceed to infect other tumor cells in the vicinity, and continue the process of tumor kill. In addition to this direct oncolytic activity, the virus carries a therapeutic payload--acting as a gene therapy vector, too--and causes the tumor cell to synthesize and secrete an immunity-stimulating protein called Interleukin-12 (IL-12) before it is killed. This IL-12 is released and promotes an immune response against surviving tumor cells, which increases the antitumor effect of the therapy. The IL-12 that is expressed can also produce an anti-angiogenic effect, by interfering with the production of new tumor blood vessels necessary to allow tumor growth. Anti-angiogenic therapies potentially starve the tumor of necessary oxygen and nutrients. Thus, the M032 oHSV produces three different potential mechanisms for antitumor effects. The virus has also been genetically-engineered to minimize the production of any toxic effects for the patient receiving the therapy.

Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma

A Phase 1 Study of M032 (NSC 733972), a Genetically Engineered HSV-1 Expressing IL-12, in Patients With Recurrent/Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma, or Gliosarcoma

National Cancer Institute (NCI)

University of Alabama at Birmingham

Principal Investigator

Participants were administered 10\^5 single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

10^5 Single Dose of HSV-1 (M032)

Participants were administered 10\^6 single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

10^6 Single Dose of HSV-1 (M032)

Participants were administered 10\^7 single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

10^7 Single Dose of HSV-1 (M032)

Participants were administered 10\^7.5 single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

10^7.5 Single Dose of HSV-1 (M032)

Participants were administered 10\^8 single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

10^8 Single Dose of HSV-1 (M032)

Participants were administered 10\^8.5 single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

10^8.5 Single Dose of HSV-1 (M032)

Participants were administered 10\^9 single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

10^9 Single Dose of HSV-1 (M032)

Participants who consented, but became ineligible prior to receiving M032

Screen Fails

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

James Markert, MD

Participants were administered 10\^5, 10\^6, 10\^7, 10\^7.5, 10\^8, 10\^8.5, or 10\^9 pfu of single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

Single Dose of HSV-1 (M032)

Maximum Tolerated Dose (MTD) of M032

Time to Progression Assessment

The Time of Survival Assessment

The Time of Biologic Assessment

Participants that consented to the study, but ended up becoming ineligible before they were given M032

Overall Study

Parvoviridae Infections

H-1PV administered at three increasing doses either intratumorally or intravenously and then 10 days after the first administration intracerebrally (into the walls of tumor resection cavity).

H-1PV

Andreas Unterberg, Prof. Dr.

Bernard Huber, Dr.

Investigation on safety, tolerability and efficacy of H-1 parvovirus (H-1PV) in subjects suffering from glioblastoma multiforme.

Investigation on safety, tolerability and efficacy of H-1 parvovirus (H-1PV) in subjects suffering from glioblastoma multiforme.

H-1PV will primarily be administered either intratumoral or intravenously. Ten days thereafter a complete or a subtotal tumor resection with a subsequent administration of H-1PV into the walls of the resection cavity will be carried out.

Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme.

Phase I/IIa Study of Intratumoral/Intracerebral or Intravenous/Intracerebral Administration of Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme.

Parameters for assessment of safety and tolerability:

* physical/neurological examinations (pathological findings as quality and quantity)
* adverse events (quality and quantity per dose level)
* vital signs, ECG, laboratory parameters (pathological findings as quality and quantity, for laboratory parameters: descriptive statistics)
* viral shedding and viral specific antibodies (quantity depicted over time)

Parameters for evaluation of efficacy:

* Progression free survival (PFS) based on modified RECIST-criteria depicted as Kaplan-Meier curve
* Overall survival (OS) depicted as Kaplan-Meier curve

Oryx GmbH & Co. KG

Antisickling Agents

Anticonvulsants

Amino Acids

Hydroxyurea

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Grade II Oligodendroglioma or oligoastrocytomas

Imatinib administered orally on daily. Imatinib is local irritant \& must be taken in sitting position; mini of 2hrs should be allowed between last drug intake \& going to bed. Imatinib doses 400mg/600mg administered once daily, whereas daily doses of 800mg/\> administered as equally divided dose taken twice day. Dose for imatinib: Pts not receiving p450-inducing antiepileptic drugs: 400 mg/day. Pts receiving p450-inducing antiepileptic drugs: 500 mg twice day. It is recommended that pts take their prescribed imatinib mesylate at same time that they take their prescribed hydroxyurea, however, 30-60min interval between agents is acceptable if required for practical/other compliance issues.

Hydroxyurea administered orally twice day. Dosing will begin on day 1 of cycle 1 \& continue daily. Drug is approximately 80 percent bioavailable. Dose will be 500mg twice day for all pts.

Imatinib Mesylate & Hydroxyurea

Annick Desjardins, MD, FRCPC

Primary objective:

* To evaluate activity of imatinib mesylate and hydroxyurea among patients with progressive/recurrent grade II low-grade glioma (LGG) as measured by 12-month progression free survival

Secondary objectives:

* To evaluate progression-free survival (PFS), overall survival and objective response rate among patients with progressive/recurrent grade II LGG treated with imatinib mesylate plus hydroxyurea
* To assess safety and tolerability of imatinib mesylate + hydroxyurea in this population

This is an open-label, single stage, uncontrolled, non-randomized Phase II study of continuous, daily doses of imatinib mesylate \& hydroxyurea in adult patients with progressive/recurrent Grade II low-grade glioma (LGG). The treatment cycle is defined as imatinib mesylate \& hydroxyurea administered daily for 28 days for purpose of scheduling evaluations. All patients who receive 1 or more doses of either imatinib mesylate or hydroxyurea will be evaluable for toxicity, whereas all patients who receive a minimum of 14 consecutive days of study regimen will be evaluable for response. Patients who discontinue therapy prior to receiving 14 consecutive days of study regimen will be regarded as ineligible for evaluation of response and will be replaced.

Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG)

Phase II Study of Imatinib Mesylate Plus Hydroxyurea in the Treatment of Patients With Recurrent / Progressive Grade II Low-Grade Glioma

Percentage of participants surviving twelve months from the start of cycle 1 without progression of disease. PFS was defined as the time from the cycle 1 start date to the date of the first documented progression according to modified Macdonald criteria, or to death due to any cause.

Time in weeks from the start of cycle 1 to the date of first progression according to modified Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

Time in weeks from the start of cycle 1 to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.

Number of participants with an objective response (complete response or partial response) based on modified Macdonald criteria.

The number of patients experiencing any serious adverse event or other (non-serious) adverse event during the study participation.

Novartis Pharmaceuticals

Duke University

All adverse events were gathered for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.

Oligodendroglioma

Age Continuous

12-month Progression Free Survival (PFS)

Median Progression-free Survival

Median overall survival was not estimable for either arm as not enough events of death occurred

Median Overall Survival (OS)

Objective Response Rate

Experienced any Serious Adverse Event

Experienced any (non-serious) Adverse Event

Safety and Tolerability of Gleevec + Hydroxyurea in Patients With Low-grade Gliomas

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

All patients will receive Border Zone Stereotactic Radiosurgery (BZ-SRS) and additionally receive bevacizumab (10 mg/kg) one day before and then at day 14 followed by 10 mg/kg/day every 14 days until progression.

One to 14 days before BZ- SRS procedure, patients at centers with MRS experience will undergo standard brain MRI /MRS

Patients will receive bevacizumab (10 mg/kg) one day before and then at day 14 followed by10 mg/kg/day every 14 days until progression.

Magnetic Resonance Spectroscopy (MRS)

The 'border zone' of the tumor will be targeted by SRS in a single session.

Border Zone Stereotactic Radiosurgery (BZ-SRS)

Ajay Niranjan, MD

This is a phase II study on the usage of stereotactic Gamma Knife radiosurgery as a boost to the tumor bed border zone in conjunction with the usage of bevacizumab.

Glioblastoma Multiforme (GBM) is the most common primary brain tumor in adults. Unfortunately, despite aggressive surgery, radiation therapy (RT) and chemotherapy, the prognosis for this disease is poor. It is our hypothesis that GBM is a "local" disease wherein treatment failure is due to failure to eradicate tumor cells in the pathways along which the tumor eventually spreads (the "border zone").

The investigators hypothesize that treatment volume escalation will be successful at improving overall survival in patients with GBM when appropriate targeting and precision dose delivery is performed in a single treatment session. The 'border zone' of the tumor will be targeted for SRS (defined as a combination of the MRI volume of gadolinium enhancement plus up to 2 cm of the surrounding T2 volume). This represents the volume of tumor infiltrated white matter and is the route of GBM spread. Bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), has been used with safety and clinical success with concomitant chemotherapy in solid tumors, including GBM.

The investigators further hypothesize that a combined approach of SRS with this VEGF inhibitor will be an effective strategy for GBM because bevacizumab will maximize the effects of radiation in the treated volume and potentially reduce radiation toxicity in the adjacent brain.

Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme

Multicenter Phase II Study of Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Multiforme

The number of months that a patient remains alive from the day first gamma knife surgery until the date of death or end of data collection for survival.

The proportion of patients who did not experience disease progression per RANO as of 6 months from the date of radiosurgery. RANO (Response Assessment in Neuro-Oncology) Response Criteria for Progression using imaging features: 25% or more increase in enhancing lesions despite stable or increasing steroid dose increase (significant) in non-enhancing FLAIR/T2W lesions, not attributable to other non-tumor causes any new lesions clinical features clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease). Proportion of patients for PFS = number of patients without disease at 6 months post radiosurgery / total number of patients.

The proportion of patients who remained alive as of 6 months from the date of radiosurgery. Proportion of patients for OS = number of patients alive at 6 months post radiosurgery / total number of patients.

The number of patients experiencing a CNS toxicity type occurring within 3 months of gamma knife surgery, as measured by RTOG/EORTC Acute Radiation Morbidity Scoring and the NCI CTCAE v4.0 for late toxicity.

Proportion of patients with a best response of CR, PR, SD, PD: number of patients with CR, PR, SD or PD / total number of patients evaluable for response to treatment of border zone Stereotactic Radiosurgery (BZ-SRS) with bevacizumab.

Improvement of border zone target selection and detection of therapeutic response of the derived treatment volumes between MRI and MRI+MRS (Magnetic Resonance Spectroscopy).

This is presented as the number of patients for whom the derived treatment was changed as a result of the utilization of MRS.

The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment. This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. Score range from 0 to 100; the lower the Karnofsky score, the worse the survival for most serious illnesses. A score of 100 would indicate 'Normal no complaints; no evidence of disease.' A score of 50 indicates 'Requires considerable assistance and frequent medical care.' A score of 0-10 would indicate 'Moribund; fatal processes progressing rapidly' and 'Death'.

The Barthel Index consists items assessing the ability to achieve certain activities without assistance. It evaluates the ability of feeding, moving from wheelchair to bed and returning, doing personal toilet, getting on and off toilet,bathing self, walking on level surface, ascending and descending stairs, dressing, controlling bowels and controlling bladder. Scoring ranged from 0 (completely dependent) to 20 (completely independent) for this assessment. A maximal score of 20 indicating that a patient is fully independent in physical functioning, and a lowest score of 0 representing a totally dependent bed-ridden state.

An assessment comprised of 20 statements for which the participant is asked to indicate how often they have felt a certain way during the past week. SCORING: zero for answers of Rarely or none of the time (less than 1 day), 1 for answers of Some or a little of the time (1-2 days), 2 for answers of Occasionally or a moderate amount of time (3-4 days) the third column, 3 for answers of Most or all of the time (5-7 days). The scoring of positive items is reversed. Possible range of scores is zero to 60, with the higher scores indicating the presence of more depression symptomatology.

The FACT-G is a patient rated, 27-item compilation of general questions divided into 4 primary Quality of Life (QOL) sub-scales: physical well-being (PWB; 7-items, score range 0-28), social/family well-being (SWB; 7-items, score range 0-28), emotional well-being (EWB; 6-items, score range 0-24), and functional well-being (FWB; 7-items, score range 0-28). This tool represents the generic core questionnaire that are utilized in combination with cancer site-specific questionnaires, (FBrain, in this study) Overall score and four subscale scores with ranges and distributions that are sample-specific can be calculated.FACT-G is scored by summing the individual scale scores; higher scores indicate better quality of life. FACT-G uses 5-point rating scale ranging from (0) = Not at all; (1) = A little bit; (2) = Somewhat; (3) = Quite a bit; to (4) = Very much.The FACT-G total score is the sum of the four subscale scores (if least 80% completed) and has a possible range of 0-108 points.

The FACT-BrSI subscale, brain tumor specific version (2007), is a 15-item, patient completed, questionnaire.This brain subscale is used along with the core (general) questionnaire (FACT-G) that includes 27 items. Patients rate all items using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Overall, higher ratings suggest higher quality of life (QOL). The FACT BrSI has a range of 0-60, where a higher score indicates less symptomatology.

Genentech, Inc.

Ajay Niranjan

Professor

All patients received Border Zone Stereotactic Radiosurgery (BZ-SRS) and additionally received bevacizumab (10 mg/kg) one day before and then at day 14 followed by 10 mg/kg/day every 14 days until disease progression. One to 14 days before BZ- SRS procedure, patients at centers with MRS experience will undergo standard brain MRI /MRS. Patients will have MRS Magnetic Resonance Spectroscopy (MRS)prior to BZ-SRS. Border Zone Stereotactic Radiosurgery (BZ-SRS): The 'border zone' of the tumor will be targeted by SRS in a single session.

BZ-SRS With Bevacizumab

Patients with recurrent or Progressive Glioblastoma Multiforme who underwent treatment of border Zone Stereotactic Radiosurgery (BZ-SRS) with bevacizumab (10 mg/kg).

Barbara Stadterman

Overall Survival (OS)

Death or disease progression ≤ 6mons of treatment

Alive or stable disease ≥ 6 months of treatment

6-month Progression-free Survival

Death within 6 months of treatment

Alive after 6 months of treatment

6-month Overall Survival

Muscle Weakness Lower Limb

Fatigue and Dehydration

Spinal Fracture and Pain

CNS Toxicity

Complete Response

Partial Response

Stable Disease

Progressed Disease

Tumor Response

Participants who received MRS (Magnetic Resonance Spectroscopy) scans prior to radiosurgery.

Potential Value of Magnetic Resonance Spectroscopy (MRS)

Karnofsky Performance Status Score: 40

Karnofsky Performance Status Score: 60

Karnofsky Performance Status Score: 70

Karnofsky Performance Status Score: 80

Karnofsky Performance Status Score: 90

Karnofsky Performance Status Score: 100

Karnofsky Performance Status

Barthel's Index of Activities of Daily Living Assessment

Center for Epidemiological Studies Depression Scale (CES-D)

Physical Well-Being

Social Well-Being

Emotional Well-Being

Functional Well-Being

Total Well-Being

Patients with recurrent or Progressive Glioblastoma Multiforme who underwent treatment of border Zone Stereotactic Radiosurgery (BZ-SRS) with bevacizumab (10 mg/kg). (NOTE: One participant did not complete the EWB section of the questionnaire. One participant did not complete the FWB section of the questionnaire.)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma	NCT02062827	Recurrent Gliob... Progressive Gli... Anaplastic Astr...	M032 (NSC 73397...	18 Years -	University of Alabama at Birmingham
Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme.	NCT01301430	Glioblastoma Mu...	H-1PV	18 Years -	Oryx GmbH & Co. KG
Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG)	NCT00615927	Glioblastoma Gliosarcoma	Imatinib Mesyla...	18 Years -	Duke University
Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme	NCT02120287	Glioblastoma Mu... Glioblastoma - ...	Bevacizumab Magnetic Resona... Border Zone Ste...	18 Years -	University of Pittsburgh
Border Zone Stereotactic Radiosurgery With Bevacizumab in Patients With Glioblastoma Multiforme	NCT02120287	Glioblastoma Mu... Glioblastoma - ...	Bevacizumab Magnetic Resona... Border Zone Ste...	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for progressive glioblastoma multiforme