Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Temozolomide

Dimethyl Fumarate

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide PO QD for 42-49 days and dimethyl fumarate PO BID or TID continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions

MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Radiation Therapy

Mark G Malkin, MD

This phase 1 trial studies the side effects and best dose of dimethyl fumarate when given together with temozolomide and radiation therapy(RT) in treating patients with newly diagnosed glioblastoma multiforme (GBM). Dimethyl fumarate may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving dimethyl fumarate with temozolomide and radiation therapy may work better in treating glioblastoma multiforme.

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of dimethyl fumarate (DMF) when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed glioblastoma multiforme (GBM).

SECONDARY OBJECTIVES:

I. To evaluate the safety, tolerance, and toxicity of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.

II. To obtain a preliminary estimate of the efficacy of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.

OUTLINE: This is a dose-escalation study of dimethyl fumarate.

CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide orally (PO) once daily (QD) for 42-49 days and dimethyl fumarate PO twice daily (BID) or thrice daily (TID) continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions.

MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 2 months thereafter.

Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Phase I Trial of Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Glioblastoma Multiforme

Subjects' treatment dosing level, dose modification, DLTs, and evaluability for DLTs and response will be listed and summarized by basic descriptive statistics (such as frequency and proportion).

Subjects' demographics, adverse events, serious adverse events, and treatment status will be listed and summarized by descriptive statistics (such as frequency, proportion, mean, standard deviation, median, and range).

The Kaplan-Meier method will be conducted to describe PFS, and median PFS will be estimated, along with 95% confidence intervals. A Cox regression model may be used to model the PFS and adjusting for any effects of potential clinical characteristics.

The Kaplan-Meier method will be conducted to describe OS, and median OS will be estimated, along with 95% confidence intervals. A Cox regression model may be used to model the OS and adjusting for any effects of potential clinical characteristics.

The clinical response rate will be calculated for each cohort, along with their corresponding 95% confidence intervals. Logistic regression may be used to model the rate by adjusting potential clinical characteristics (such as age, gender, and tumor grade). Mean and standard deviation of duration of response (overall response, complete response, and stable disease, respectively), along with its 95% confidence interval, will be estimated based on the method proposed by Ellis et al. via the exponential distribution.

National Cancer Institute (NCI)

Virginia Commonwealth University

Symptoms and General Pathology

Nervous System Diseases

Recurrence

Brain Neoplasms

Disease Attributes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antibodies

Antibodies, Bispecific

Immunoglobulins

Muromonab-CD3

PHASE I: Patients receive EGFRBi-armed autologous T cells IT twice weekly for 4 weeks.

PHASE II: Patients receive EGFRBi-armed autologous T cells\* IT twice weekly for 4 weeks and then IV over 15-30 minutes twice weekly for 2 weeks.

\*NOTE: Six selected patients receive EGFRBi-armed autologous T cells IV on day -3, -2, or -1 prior to first IT infusion.

EGFRBi-Armed Autologous T Cells

Laboratory Biomarker Analysis

Sandeep Mittal

This phase I/II trial studies the side effects and best dose of epidermal growth factor receptor bispecific antibody (EGFRBi)-armed autologous T cells and how well it works in treating patients with glioblastoma that have come back or does not respond to treatment. EGFRBi-armed autologous T cells coated with antibodies (proteins used by the immune system to target and kill foreign objects such as cancer cells) may have great ability to seek out, attach to, and destroy glioblastoma cells.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) for 8 intrathecal (IT) injections (via lumbar puncture) of anti-cluster of differentiation (CD)3 × anti-EGFRBi armed activated T cells (aATC) (EGFRBi-armed autologous T cells) given twice per week for 4 weeks in a standard 3+3 dose escalation schema with 0.10, 0.50 and 1.00 × 10\^9 EGFRBi-aATC per IT injection for a total of 0.8, 4.0, and 8.0 × 10\^9 cells, respectively. (Phase I) II. To explore efficacy and confirm the toxicity profile of EGFRBi-aATC. (Phase II)

SECONDARY OBJECTIVES:

I. Measure immune responses in participants of the phase I/II trial by sequential monitoring of phenotype, interferon gamma (IFN-g) enzyme-linked immunoSpots (EliSpots), anti-glioblastoma (GBM) cytotoxicity of peripheral blood mononuclear cell (PBMC) (direct cytotoxicity against GBM cells) directed at GBM cell lines, T-helper 1 (Th1)/T-helper 2 (Th2) serum cytokine patterns, and anti-glioma antibodies in the cerebrospinal fluid (CSF)/serum during the "vaccinate and consolidate" process.

II. Assess survival and persistence of aATC in the CSF, and trafficking of IT-injected aATC out of the CSF into the bloodstream.

III. Image patients' brain with magnetic resonance imaging (MRI) (performed clinically in 2-month intervals; includes standard structural sequences and perfusion imaging) and alpha-\[11C\]methyl-L-tryptophan (AMT) positron emission tomography (PET) scan (under Wayne State University \[WSU\] Internal Review Board \[IRB\]/Karmanos Cancer Institute \[KCI\]-approved research protocol) before and after the aATC treatment regimen.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

PHASE I: Patients receive EGFRBi-armed autologous T cells IT twice weekly for 4 weeks.

PHASE II: Patients receive EGFRBi-armed autologous T cells\* IT twice weekly for 4 weeks and then intravenously (IV) over 15-30 minutes twice weekly for 2 weeks.

\*NOTE: Six selected patients receive EGFRBi-armed autologous T cells IV on day -3, -2, or -1 prior to first IT infusion.

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

EGFRBi-Armed Autologous T Cells in Treating Patients With Recurrent or Refractory Glioblastoma

Targeting Recurrent Glioblastoma With Anti-CD3 x Anti-EGFR Bispecific Antibody Armed T Cells: A Phase I/II Study

Will be evaluated whether the infused cells persist in vivo using fluorescence-activated cell sorting analysis for the mouse immunoglobulin G 2 alpha (IgG2a) (OKT3 part of the EGFRBi).

The median OS will be estimated with 95% confidence interval. Kaplan-Meier estimate of OS will be plotted. For quantitative measurements in immune evaluations, will calculate their means, standard deviations, medians, and examine the distributions of these data to ascertain whether normal theory methods are appropriate. Paired t-test or Wilcoxon signed-ranks test will be used for comparative analyses between each post-IMT time point versus pre-IMT.

Mean, standard deviation, median and examine the distributions of these data will be calculated to ascertain whether normal theory methods are appropriate. Paired t-test or Wilcoxon signed-ranks test will be used for comparative analyses between each post-IMT time point versus pre-IMT. Bonferroni's adjusted p-values will be reported to control type I error rate. In addition, will assess the pattern of changes in the immune responses over time using graphical techniques such as LOWESS curves.

Serial serum samples will be tested and evaluated for the development of immunoglobulin G (IgG) and IgM anti-mouse antibody responses.

Barbara Ann Karmanos Cancer Institute

Principal Investigator

Patients receive methoxyamine PO QD and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

Methoxyamine

Manmeet Ahluwalia

This phase II trial studies how well methoxyamine works when added to standard temozolomide in treating patients with glioblastoma that has come back. Drugs used in chemotherapy, such as methoxyamine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

PRIMARY OBJECTIVES:

I. To estimate the efficacy of TRC102 (methoxyamine) and temozolomide, as measured by response rate, in bevacizumab naïve glioblastoma. (Arm I) II. To estimate the efficacy of TRC102 and temozolomide, as measured by response rate, in bevacizumab refractory glioblastoma. (Arm II)

SECONDARY OBJECTIVES:

I. Evaluate the toxicities of oral TRC102 and temozolomide in this patient population.

II. Estimate the efficacy of TRC102 and temozolomide, as measured by progression-free survival, progression-free survival at 6 months and overall survival, in bevacizumab naïve glioblastoma.

III. Estimate the efficacy of TRC102 and temozolomide, as measured by progression-free survival in bevacizumab refractory glioblastoma.

TERTIARY OBJECTIVES:

I. Assess the tissue correlates of N-methylpurine-deoxyribonucleic acid (DNA) glycosylase (MPG), topoisomerase II-alpha (topo II a), and O-6-methylguanine-DNA methyltransferase (MGMT) status, with response, progression-free survival (PFS), and overall survival.

OUTLINE:

Patients receive methoxyamine orally (PO) once daily (QD) and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days, every 2 months for 2 years, and then every 6 months thereafter.

Methoxyamine and Temozolomide in Treating Patients With Recurrent Glioblastoma

Phase II Study of TRC102 in Combination With Temozolomide for Recurrent Glioblastoma

MPG, topo II-alpha, and MGMT levels will be correlated with response, PFS, and overall survival. Will be analyzed using standard descriptive statistical methods.

To test the hypothesis that the combination treatment of temozolomide and methoxyamine will achieve 30% radiographic response rate (partial response + complete response) in patients with first recurrence of glioblastoma.

Per Response Assessment in Neuro-Oncology (RANO) Criteria: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Number of participants who experience adverse events graded 3 or higher as defined by National Cancer Institute CTCAE v4.0.

Will be analyzed using standard descriptive statistical methods. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Will be analyzed using standard descriptive statistical methods.

Patients receive methoxyamine PO QD and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Treatment (Methoxyamine, Temozolomide)

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Higher score better 100 normal no complaints/disease 90 capable normal activity few symptoms/disease 80 normal activity, some difficulty some symptoms/signs 70 caring for self not capable normal activity/work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care/help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures/treatment 10 moribund rapidly progressive fatal disease processes 0 death

Karnofsky Performance Score (KPS)

n for this study 31 subjects w/ a 2 stage design. 19 subjects were treated in stage one with TRC102 and TMZ in recurrent GBM. If no more than 2 responses were observed among the initial 19 patients the study would be terminated and declared negative

Sr. Research Program Manager

Patients receive methoxyamine PO QD and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Bevacizumab-naïve)

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Arm1 Methoxyamine&Temozolomide (Bevacizumab-naïve)

Patients receive methoxyamine PO QD and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab-refractory

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Arm2 Methoxyamine&Temozolomide (Bevacizumab-refractory)

This was a 2 stage design study. if there were less than 2 responders in first 19 subjects, study would terminate and Arm2 would not accrue any subjects.

Objective Response as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria (Arm 1 and Arm 2)

Patients receive methoxyamine PO QD and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment (methoxyamine, temozolomide): Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Toxicity as Assessed by Number of Participants Who Experienced Adverse Events

Progression-free Survival

Progression-free Survival at 6 Months

Overall Survival

Data was not collected to assess this outcome measure.

MPG, Topo II-alpha, and MGMT Levels in Tissue Samples

Patients receive methoxyamine PO QD and temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab-naive

Laboratory Biomarker Analysis: Correlative studies

Methoxyamine: Given PO

Temozolomide: Given PO

Arm1 Methoxyamine &Temozolomide (Bevacizumab-naïve)

Arm2 Methoxyamine & Temozolomide (Bevacizumab-refractory)

Overall Study

Hematinics

Pharmaceutical Solutions

Ferrosoferric Oxide

Parenteral Nutrition Solutions

Patients receive ferumoxytol non-stoichiometric magnetite IV on day 2 then undergo DSC MRI, and DCE MRI, DWI (day 1 only), and TOF MR angiography on days 1-3 at 4 time points: before radiation, 3 weeks after initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose). Ferumoxytol non-stoichiometric magnetite administration continues in the absence of unacceptable toxicity.

Patients receive gadoteridol IV on day 1 then undergo DSC MRI, and DCE MRI, DWI (day 1 only), and TOF MR angiography on days 1-3 at 4 time points: before radiation, 3 weeks after initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose).

Gadolinium

Ferumoxytol Non-Stoichiometric Magnetite

Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Diffusion Weighted Imaging

MRI-Based Angiogram

Edward Neuwelt

This pilot clinical trial studies how a magnetic resonance imaging (MRI) study with ferumoxytol works as a contrasting agent in assessing early response in patients with glioblastoma multiforme receiving temozolomide and radiation therapy. Ferumoxytol is a very small form of iron particles that are injected into the body and taken up by certain tissues which may make these tissues easier to see during imaging. Diagnostic procedures, such as an MRI study with ferumoxytol, may help measure a patient's response to earlier treatment.

PRIMARY OBJECTIVES:

I. To characterize glioblastoma multiforme (GBM) tumor vascular properties using ferumoxytol (ferumoxytol non-stoichiometric magnetite) and compare to those obtained using gadolinium (Gd) based MRI contrast agent.

II. To characterize vascular changes in GBM tumors associated with standard radio/chemotherapy.

SECONDARY OBJECTIVES:

I. Cerebral blood flow (CBF), mean transit time (MTT), and time-to-peak (TTP) perfusion parameters will be measured for each contrast agent and evaluated in post-hoc analysis.

II. To obtain qualitative assessment of tumor vascularity using time-of-flight (TOF) magnetic resonance (MR) angiography techniques.

III. To characterize changes in the apparent diffusion coefficient (ADC) of tumor water associated with standard radio/chemotherapy in GBM.

OUTLINE:

Patients receive gadolinium intravenously (IV) on day 1 and ferumoxytol non-stoichiometric magnetite IV on day 2 then undergo dynamic susceptibility contrast enhanced (DSC) MRI, and dynamic contrast enhanced (DCE) MRI, diffusion-weighted imaging (DWI) (day 1 only), and TOF MR angiography on days 1-3 at 4 time points: before radiation, 3 weeks after initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose). Ferumoxytol non-stoichiometric magnetite administration continues in the absence of unacceptable toxicity. Patients also receive temozolomide and undergo radiation therapy per standard of care.

After completion of ferumoxytol non-stoichiometric magnetite administration, patients are followed up for 4-6 weeks and then periodically until the resolution or stabilization of unacceptable toxicities.

MRI Study With Ferumoxytol in Assessing Early Response in Patients With Glioblastoma Multiforme Receiving Temozolomide and Radiation Therapy

Early Assessment of Tumor Response to Therapy Using Ferumoxytol (Code 7228) as an MR Contrast Agent in Patients With Glioblastoma Multiforme (MedDRA Code 10018337)

Radiographical progression is determined based on RANO criteria.

Tumor progression was assessed by RANO criteria (Wen, 2010).

OHSU Knight Cancer Institute

Professor

Subjects all received ferumoxytol enhanced MR on day 1, ferumoxytol enhanced MR on day 2, and delayed MR imaging on day 3 - this 3 day sequence of imaging was repeated at four time points

Ferumoxytol

Subjects all received gadolinium enhanced MR on day 1, ferumoxytol enhanced MR on day 2, and delayed MR imaging on day 3 - this 3 day sequence of imaging was repeated at four time points

Gadoteridol

Gadoteridol With Leakage Correction

Subjects all received gadolinium enhanced MR on day 1, ferumoxytol enhanced MR on day 2, and delayed MR imaging on day 3 - this 3 day sequence of imaging was repeated at four time points.

Gadoteridol + Ferumoxytol Contrast Agent

Age, Categorical

Age, Continuous

Dr. Edward Neuwelt

Patients receive gadolinium IV on day 1 and ferumoxytol non-stoichiometric magnetite IV on day 2 then undergo DSC MRI, and DCE MRI, DWI (day 1 only), and TOF MR angiography on days 1-3 at 4 time points: before radiation, 3 weeks after initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose).

Gadoteridol Leakage Correction

All patients with treated GMB showed apparent tumor progression on conventional MR images.

Mean Cerebral Blood Volume (CBV)

Tumor Progression on Conventional MR

Anti-Infective Agents

Gastrointestinal Agents

Bevacizumab

Molgramostim

Sargramostim

Vaccines

Immunomodulating Agents

Poly I-C

Carboxymethylcellulose Sodium

Poly ICLC

Imiquimod

Monatide (IMS 3015)

Adjuvants, Vaccine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Adjuvants, Immunologic

Interferons

Antiviral Agents

Laxatives

Cathartics

Patients will receive SL-701 with the vaccine adjuvants granulocyte macrophage-colony stimulating factor (GM-CSF) injection and imiquimod topical cream.

A complete dose of study drug consists of the administration of a sequence of 3 agents, SL-701 emulsion SC injection, GM-CSF SC injection, and imiquimod topical cream, within a 5-minute time frame. Topical application of imiquimod cream at the injection site is repeated at 24 hours after each SL-701 emulsion injection. For each patient, SL-701 emulsion (SL-701 in Montanide®) will be administered by SC injection beginning on Day 1 with imiquimod topical cream 5% applied immediately (within 5 minutes after SL-701 emulsion injection) to the SL-701 emulsion injection site.

In addition to the SL-701 emulsion injection, the patient will receive a SC injection of GM-CSF 150 μg close to the injection site of SL-701 emulsion. An additional dose of imiquimod cream will be applied at the same site by the patient 24 hours later.

SL-701 emulsion and the adjuvant poly-ICLC will be administered twice weekly for the initial 2 weeks, every 7 days during the subsequent 3 doses, and subsequently every 14 days for the subsequent 9 doses (16 doses total) through Week 22, and every 4 weeks thereafter. Bevacizumab will be administered every 2 weeks, subsequent to the administration of SL-701/poly-ICLC.

1.0 mL injection taken from 0.7 mL of SL-701 mixed at a 1:1 (v/v) ratio with 0.7 mL of Montanide. Preferred site of SC injection is in the right or left upper arms.

Within 20 minutes following the administration of the SL-701 emulsion, poly-ICLC should be administered as an IM injection in the same extremity (within 3 cm whenever possible) as was administered the SL-701 (deltoid muscle, unless contraindicated).

SL-701; poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethyl cellulose)

Following the administration of SL-701 and poly-ICLC, bevacizumab will be administered IV at a dose of 10 mg/kg. Bevacizumab infusions may occur over 30, 60 or 90 minutes in accordance with institutional practices and guidelines.

1.0 mL injection taken from 0.7 mL of SL-701 mixed at a 1:1 (v/v) ratio with 0.7 mL of Montanide. Preferred site of SC injection is in the right or left upper arms.

150 μg GM-CSF should be administered as a SC injection immediately after SL-701 emulsion administration and within 1 cm from the center of the SL-701 emulsion injection site.

SL-701 + GM-CSF

Within 5 minutes following the administration of the SL-701 emulsion, approximately 125 mg of imiquimod cream will be applied topically on the injection site. The imiquimod cream should be rubbed in until the cream is no longer visible.

The purpose of this study is to determine the safety and efficacy of SL-701 as a treatment for recurrent glioblastoma multiform (GBM).

This is a multicenter, open-label Phase 1/2 study evaluating the efficacy and safety of SL-701 as a treatment for recurrent GBM, divided into 2 stages. Seventy-four (74) patients were treated in the study, 46 in Stage 1 and 28 in Stage 2, men and women at least 18 years of age, all of whom showed unequivocal evidence of either a first tumor recurrence or progression during or following an initial treatment regimen before enrollment in this study. At least 54 of the 74 treated patients had measurable disease based on contrast-enhanced magnetic resonance imaging or computed tomography scans.

Safety and Efficacy Study of SL-701, a Glioma-Associated Antigen Vaccine To Treat Recurrent Glioblastoma Multiforme

A Phase 1/2 Study of SL-701, a Subcutaneously Injected Multivalent Glioma-Associated Antigen Vaccine, in Adult Patients With Recurrent Glioblastoma Multiforme (GBM)

OS-12 after the initiation of SL-701, per Kaplan-Meier estimate.

The ORR was the percentage of subjects who had at least 1 overall tumor response of CR or PR documented on 2 consecutive MRIs ≥4 weeks apart by modified Response Assessment in Neuro-Oncology criteria.

Measure the number of subjects with a CR or PR. A CR requires all of the following: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patients must be off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. A PR requires all of the following: ≥50% decrease, compared with baseline; the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no progression of nonmeasurable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on the same or a lower dose of corticosteroids compared with baseline scan; and the patient being on a corticosteroid dose not greater than the dose at time of the baseline scan and stable or improved clinically.

Estimate the percent of patients alive and progression-free survival at 6 months (PFS-6) after the initiation of SL-701.

Stemline Therapeutics, Inc.

Patients received SL-701 with the vaccine adjuvants GM-CSF injection and imiquimod topical cream.

A complete dose of study drug consisted of the administration of a sequence of 3 agents, SL-701 emulsion SC injection, GM-CSF SC injection, and imiquimod topical cream, within a 5-minute time frame. Topical application of imiquimod cream at the injection site was repeated at 24 h after each SL-701 emulsion injection. For each patient, SL-701 emulsion (SL-701 in Montanide®) was administered by SC injection beginning on Day 1 with imiquimod topical cream 5% applied immediately (within 5 minutes after SL-701 emulsion injection) to the SL-701 emulsion injection site.

In addition to the SL-701 emulsion injection, the patient received a SC injection of GM-CSF 150 μg close to the injection site of SL-701 emulsion (immediately following the SL-701 emulsion injection, before the application of topical imiquimod). An additional dose of imiquimod cream was applied at the same site by the patient 24 h later.

SL-701; GM-CSF; Imiquimod

SL-701 emulsion and the adjuvant poly-ICLC was administered twice weekly for the initial 2 weeks, every 7 days during the subsequent 3 doses, and subsequently every 14 days for the subsequent 9 doses (16 doses total) through Week 22, and every 4 weeks thereafter. Bevacizumab was administered every 2 weeks, after the administration of SL-701/poly-ICLC.

SL-701; poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethyl cellulose): Within 20 minutes following the administration of the SL-701 emulsion, poly-ICLC was administered as an IM injection in the same extremity (within 3 cm whenever possible) as was administered the SL-701 (deltoid muscle, unless contraindicated).

Bevacizumab: Following the administration of SL-701 and poly-ICLC, bevacizumab was administered IV at a dose of 10 mg/kg. Bevacizumab infusions occurred over 30, 60 or 90 minutes in accordance with institutional practices and guidelines.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme	NCT02337426	Adult Brain Gli... Adult Giant Cel... Adult Gliosarco...	Dimethyl Fumara... Temozolomide Radiation Thera...	18 Years -	Virginia Commonwealth University
EGFRBi-Armed Autologous T Cells in Treating Patients With Recurrent or Refractory Glioblastoma	NCT02521090	Adult Brain Gli... Adult Gliosarco... Recurrent Brain...	EGFRBi-Armed Au... Laboratory Biom...	18 Years -	Barbara Ann Karmanos Cancer Institute
Methoxyamine and Temozolomide in Treating Patients With Recurrent Glioblastoma	NCT02395692	Adult Brain Gli...	Treatment Methoxyamine Temozolomide	18 Years -	National Cancer Institute (NCI)
Methoxyamine and Temozolomide in Treating Patients With Recurrent Glioblastoma	NCT02395692	Adult Brain Gli...	Treatment Methoxyamine Temozolomide	18 Years -	National Cancer Institute (NCI)
MRI Study With Ferumoxytol in Assessing Early Response in Patients With Glioblastoma Multiforme Receiving Temozolomide and Radiation Therapy	NCT00660543	Adult Brain Gli...	Gadolinium Ferumoxytol Non... Dynamic Contras... Dynamic Suscept... Diffusion Weigh... MRI-Based Angio...	18 Years -	OHSU Knight Cancer Institute
Safety and Efficacy Study of SL-701, a Glioma-Associated Antigen Vaccine To Treat Recurrent Glioblastoma Multiforme	NCT02078648	Adult Brain Gli... Glioblastoma Mu...	SL-701; poly-IC... Bevacizumab SL-701 + GM-CSF Imiquimod	18 Years -	Stemline Therapeutics, Inc.
EGFRBi-Armed Autologous T Cells in Treating Patients With Recurrent or Refractory Glioblastoma	NCT02521090	Adult Brain Gli... Adult Gliosarco... Recurrent Brain...	EGFRBi-Armed Au... Laboratory Biom...	18 Years -	Barbara Ann Karmanos Cancer Institute
MRI Study With Ferumoxytol in Assessing Early Response in Patients With Glioblastoma Multiforme Receiving Temozolomide and Radiation Therapy	NCT00660543	Adult Brain Gli...	Gadolinium Ferumoxytol Non... Dynamic Contras... Dynamic Suscept... Diffusion Weigh... MRI-Based Angio...	18 Years -	OHSU Knight Cancer Institute

Spots Global Cancer Trial Database for adult brain glioblastoma