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

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Irinotecan

Osimertinib

Everolimus

Temozolomide

Lomustine

Lapatinib

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Patients with newly found supratentorial lesions, or patients previously diagnosed with supratentorial gliomas at time of recurrence, whose treatment plan includes partial or total resection surgery as a component of standard-of-care treatment will be included.

- Placement of 1-3 microdevices (depending on the size of the tumor) before tumor resection is started.

-- The microdevices will dwell in the tumor tissue for a time window of 2-4 hours to allow time for tissue effects of the drugs microdoses for intratumor release of the following 8 approved drugs: Temozolomide, Lomustine, Irinotecan, Carboplatin, Lapatinib, Osimertinib, Abenaciclib, and Everolimus. The drugs used in this study will only include drugs already used systemically for the treatment of gliomas.

Placement of 1-3 microdevices (depending on the size of the tumor) before tumor resection is started.

The microdevices will dwell in the tumor tissue for a time window of 2-4 hours to allow time for tissue effects of the drugs (Temozolomide, Lomustine, Irinotecan, Carboplatin, Lapatinib, Osimertinib, Abenaciclib, and Everolimus) released by the microdevice reservoirs. The drugs used in this study will only include drugs already used systemically for the treatment of gliomas.

Microdevice

Pier Paolo Peruzzi, MD, PhD

This pilot study will assess the safety and feasibility of using an implantable microdevice to measure local intratumor response to chemotherapy and other clinically relevant drugs in malignant brain tumors.

* The device involved in this study is called a microdevice.
* The drugs used in this study will only include drugs already used systemically for the treatment of gliomas.

This research study is a Pilot Study, which is the first time investigators are examining this study device in brain tumors.

The FDA (the U.S. Food and Drug Administration) has not approved the microdevice as a treatment for any disease.

Investigators are studying the safety of the microdevice and the effects of different drugs for each specific tumor. Brain tumors are known to be very different from each other and respond differently to different drugs. It would be very helpful to find out what drugs have the best chance of working in each specific tumor.

This research study involves drugs that are released by a small device, as small as the tip of a needle, that is inserted into the tumor at the time of surgery and is removed at the end of the surgery. The goal of this research study is to prove that microdevices can be used to find out which drugs have better effects on treating malignant brain tumors.

Participants will be in this research study for up to 30 days.

Expected enrollment is about 12 people.

Implantable Microdevice In Primary Brain Tumors

A Pilot Study of an Implantable Microdevice for In Situ Evaluation of Drug Response in Patients With Primary Brain Tumors

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Defined as the ability to retrieve the microdevice with sufficient tissue, of sufficient quality, for downstream histopathology analysis and interpretation of at least 50% of the microdevice reservoirs.

Failure" from a safety standpoint will be considered any of the following:

* Any grade 3 or higher adverse events associated with microdevice placement or retrieval.
* Any combination of more than two grade 2 adverse events.

Failure" from a safety standpoint will be considered any of the following:

two-tailed alpha level of 0.05 and report 95% confidence intervals with any point estimates

Preliminary correlations between a specific genetic feature and drug response will be tested using the Chi-squared/Fisher's exact test for categorical variables or the T-test or Wilcoxon Rank-Sum test for continuous variables.

Oliver Jonas, PhD

Sponsor Investigator

Symptoms and General Pathology

Recurrence

Antirheumatic Agents

Immunomodulating Agents

Interleukin-4

Adjuvants, Immunologic

Immunologic Factors

Single infusion of MDNA55 via convection enhanced delivery (CED).\*

\*Subjects may be eligible to receive a second administration of MDNA55.

MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).

MDNA55

This is a single-arm, open-label, multicenter study in approximately 52 adults with primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence) after treatment(s) including surgery and radiotherapy with or without chemotherapy and following discontinuation of any previous standard or investigational lines of therapy.

The study drug, MDNA55, is a fusion protein comprising a genetically engineered Interleukin-4 (IL-4) linked to a modified version of the Pseudomonas aeruginosa exotoxin A (PE). MDNA55 binds to the IL-4 receptor (IL4R), over-expressed by cancer cells and non-malignant immunosuppressive cells of the tumor microenvironment (TME), and delivers a potent cell-killing agent, PE.

The study will be conducted at up to 10 clinical sites following institutional review board approval and completed informed consent.

Subjects that meet the study eligibility criteria will undergo surgery associated with study drug administration. MDNA55 will be administered locally by convection-enhanced delivery (CED).

Post-treatment follow-up assessment of safety and efficacy will be performed monthly for the first 6 months and bimonthly thereafter for approximately 1 year after study drug administrations. Subjects will continued to be followed for survival and post-study treatment(s) of GB after study completion or withdrawal.

Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

An Open-Label Non-Randomized, Multi-Center Phase-2 Study of Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

Number of Subjects with Serious adverse events with Frequency \>=5%

Incidence of Treatment-Emergent adverse events

Systemic exposure to MDNA55 is not expected following intratumoral infusion and circulating MDNA55 has not been detected in previous clinical studies. To continue to evaluate the potential of systemic exposure, plasma collected at screening (baseline), within 1 hour following infusion end time, \~3 hours following completion of infusion and then (after the \~3 hour sample collection) every 6 hours ± 2 hours until 24 hours and at Day 14. PK data will be presented for the PK population in listing format by subject and sample collection time point. PK parameters would only be analyzed if MDNA55 levels above LLOQ (0.37 ng/mL) were detected.

Number of participants that were ADA Positive and had Neutralizing Antibody

Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies versus the alternative hypothesis of 11.5 months.

ORR, determined by independent central review (per RANO-based criteria) Complete Response - Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks.

Partial Response - ≥50% decrease in sum of products of perpendicular diameters or ≥65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks Progressive Disease - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions.

Stable Disease - Does not qualify for CR, PR, or PD as defined above

PFS, time from treatment until disease progression (per RANO-based criteria) or death Progressive Disease per RANO - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions

Medicenna Therapeutics, Inc.

All patients were included in the in the ITT / Safety Population (N=47) for "MDNA55 (Overall)"; there is one patient that underwent catheter placement but did not receive the study drug; the infusion did not proceed due to catheter misplacement. Therefore, this participant is not included in the individual MDNA55 infusion arms (N=46)

Single infusion of MDNA55 administered via Convection Enhanced Delivery (CED) Dose conc. range 1.5 to 9.0 mcg/mL; total dose range 18 to 240 mcg

MDNA55 (Overall)

Single infusion of MDNA55 administered via Convection Enhanced Delivery (CED) Dose conc. 1.5 mcg/mL

MDNA55 (1.5 mcg/mL)

Single infusion of MDNA55 administered via Convection Enhanced Delivery (CED) Dose conc. 3.0 mcg/mL

MDNA55 (3.0 mcg/mL)

Single infusion of MDNA55 administered via Convection Enhanced Delivery (CED) Dose conc. 6.0 mcg/mL

MDNA55 (6.0 mcg/mL)

Single infusion of MDNA55 administered via Convection Enhanced Delivery (CED) Dose conc. 9.0 mcg/mL

MDNA55 (9.0 mcg/mL)

Subjects received a single infusion of MDNA55 (via convection enhanced delivery) at concentrations ranging from 1.5 to 9.0 μg/mL and volumes ranging from 12 to 66 mL (total dose between 18 to 240 mcg)

Age (years)

Age, Customized

Sex: Female, Male

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Race/Ethnicity, Customized

Ethnicity

Karnofsky Performance Score (KPS)

o6-methylguanine-DNA-methyltransferase (MGMT) Status

Steroid Use

Biopsy

Diagnostic method of Glioblastoma

Initial Surgery - Total Resection

Initial Surgery - Partial Resection

Initial Surgery - Other

Additional Surgery - Resection

Additional Surgery - Debulking

Additional Surgery - Other

Radiotherapy

Other Chemotherapy

Investigational

Prior Glioblastoma treatment

Initial diagnosis to 1st relapse

Max tumor diameter at initial diagnosis

1st relapse

2nd relapse

Number of prior relapse

Tumor volume at baseline

Maximum tumor diameter at baseline

Lymphocyte Count

Intent-to-Treat and Safety: ITT and Safety populations were identical and consisted of all subjects who signed an informed consent form and received any amount of study drug.

Rosemina Merchant - Chief Development Officer

All subjects enrolled, received any amount of study drug

MDNA55 (ITT Analysis)

In support of the primary efficacy analysis, evaluation of the primary endpoint was also conducted on the PP population.

MDNA55 (PP Analysis)

Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies.

ITT/Safety population: all subjects who signed an informed consent form and received any amount of study drug.

Per-Protocol Population: all subjects in the ITT Population who had no major protocol violation during the study.

Primary efficacy analysis was not performed for individual dose concentrations.

Overall Survival (OS)

Single infusion of MDNA55 via convection enhanced delivery (CED).\*

\*Subjects may be eligible to receive a second administration of MDNA55.

MDNA55: MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).

Modified Intent-to-Treat Population (mITT): mITT population was used for secondary response analyses and consisted of all subjects who received any amount of study drug, had adequate imaging (at least 1 post-treatment scan), and had sufficient clinical data for ORR analysis.

Objective Response Rate (ORR)

Progression Free Survival (PFS)

Single infusion of MDNA55 via convection enhanced delivery (CED).

MDNA55: MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).

Number of Subjects With Serious Adverse Events

Treatment Emergent Adverse Events

Pharmacokinetic (PK) Population: Subjects who received the highest concentrations (6 μg/mL and 9 μg/mL) were analysed first. If all results were shown to be below lower limit of quantitation (LLOQ) of 0.37 ng/mL, consistent with historical data showing no evidence of systemic exposure with MDNA55, then no further subjects were to be analyzed. All subjects analyzed had levels of MDNA55 that were below lower limit of quantitation (LLOQ) of 0.37 ng/mL

Level of MDNA55 in Peripheral Plasma

ADA positive

Neutralizing Antibody (NAb)

Anti-Drug-Antibody (ADA) Population: ADA population included all subjects who received any dose of study drug and had a pre-treatment baseline blood sample and at least one post-treatment blood sample available for determination of ADA. Neutralizing antibody (NAb) titers were assessed in the ADA population as appropriate and applicable.

ADA Titer / Neutralizing Antibody Analysis

Subjects received a single infusion of MDNA55 (via convection enhanced delivery) at concentrations ranging from 1.5 to 9.0 μg/mL. Total dose administered did not exceed 240 μg (the established maximum tolerated dose \[MTD\]).

Overall Study

Vaccines

All patients will receive the full TVI-Brain-1 treatment.

Following surgery, tumor tissue is used to generate a cancer vaccine. Patients are vaccinated with neutralized cells to initiate an immune response. Following vaccinations, the patient's white blood cells are collected, the white blood cells are stimulated and expanded, and are then reinfused into the patient's blood.

TVI-Brain-1

Gary Wood, Ph.D.

TVI-Brain-1 is an experimental treatment that takes advantage of the fact that your body can produce immune cells, called 'killer' white blood cells that have the ability to kill large numbers of the cancer cells that are present in your body. TVI-Brain-1 is designed to generate large numbers of those 'killer' white blood cells and to deliver those cells into your body so that they can kill your cancer cells.

The TVI-Brain-1 treatment involves several steps. First, the patient's cancer will be surgically removed to provide cells for the vaccine. Second, the patient will be vaccinated with the vaccine formulation. Third, the patient's blood will be filtered for killer T cell precursors which will then be cultured and stimulated to reach a higher (killer) activity level. Fourth, the activated cells will be infused into the patient's bloodstream so that they will be able to attack the cancer.

Study To Test the Safety and Efficacy of TVI-Brain-1 As A Treatment for Recurrent Grade IV Glioma

Phase 2 Study To Test The Safety and Efficacy of TVI-Brain-1 As A Treatment For Recurrent Grade IV Glioma

To assess the efficacy of TVI-Brain-1 on patients to evaluate progression free survival. MRI data is used to evaluate tumor progression; success is defined if a patient is still alive and has \< 25 % increase in Tumor volume in MRI collected at 6 month timepoint.

All patients will be followed until death or the end of the study to measure overall survival.

Toxicity will be assessed throughout the study by recording clinical symptoms, performing physical examinations, measuring vital signs and performing clinical laboratory tests, including complete blood counts and differentials, blood chemistries and autoimmune profiles.

Time to progression is defined date of evidence of increase in tumor volume as evaluated by review and analysis of imaging, using MacDonald Criteria in review of serial MRI's taken at specific timepoints

Time to progression is defined as assessed by neurologists and radiologists evaluation of time to worsening of patient's neurological status and/or increase in tumor volume measurements as evaluated by review and analysis of serial physical exams and MRI's taken at specific timepoints

Skin Test using attenuated autologous cancer cells will be performed to assess the immunogenicity of the Subject's cancer.

Evidence of a Resulting wheal or flare reaction from sub-cutanous injection of test will be evaluated in each patient

Quality of life data using the FACT-Br score tabulation from responses on validated tool

TVAX Biomedical

Adverse events were collected at all clinic visits through evaluation of blood chemistry and hematology labs, vital sign measurements, physical exams, and direct patient questioning.

All patients will receive the full TVI-Brain-1 treatment.

TVI-Brain-1: Following surgery, tumor tissue is used to generate a cancer vaccine. Patients are vaccinated with neutralized cells to initiate an immune response. Following vaccinations, the patient's white blood cells are collected, the white blood cells are stimulated and expanded, and are then reinfused into the patient's blood.

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Recruitment was stopped to allow a change in protocol design. Some positive clinical effects were observed but this study design treated Subjects whose cancers have progressed following surgery, radiotherapy, and temozolomide chemotherapy and therefore have immune systems that are too compromised to allow maximal benefit from the use of TVI-Brain-1. Study #008 is changed to treat newly diagnosed Subjects with healthy immune systems and minimal residual disease.

Michael E. Salacz,MD and David Tran,MD, PH.D

Progression of Disease

Overall Survival

Toxicity was assessed throughout the study by recording clinical symptoms, physical examinations, vital signs, clinical laboratory tests, including blood counts and differentials, blood chemistries and autoimmune profiles. Patients were monitored for toxicities during the study and for one month following removal from the study for any reason.

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Time to Progression of Tumor Per MRI

Objective Response Rate

Delayed-type Hypersensitivity (DTH) Skin Testing

Quality of Life as Measured by FACT-Br Tool Score

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Erlotinib HCl (OSI-774)

Barbara Klencke, M.D.

This is a Phase II, open-label, multicenter trial of single-agent treatment with Tarceva in patients with histologically confirmed GBM in first relapse. This study seeks to estimate the objective response rate and will investigate whether response rate is related to EGFR amplification status.

A Study of the Safety and Efficacy of Tarceva in Patients With First Relapse of Grade IV Glioma (Glioblastoma Multiforme)

A Phase II, Multicenter, Open-Label Trial of the Safety and Efficacy of Tarceva (Erlotinib Hydrochloride) in Patients With First Relapse of Grade IV Glioma (Glioblastoma Multiforme)

Genentech, Inc.

Bevacizumab

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

Safety Cohort: The first 6 participants will receive Hypofractionated Stereotactic Irradiation (HFSRT) followed by Ipilimumab + Nivolumab + Bevacizumab.

Dose Expansion Cohort: All 26 participants will be treated with Hypofractionated Stereotactic Irradiation (HFSRT), followed by Ipilimumab + Nivolumab +Bevacizumab

Hypofractionated Stereotactic Irradiation (HFSRT) prior to nivolumab.

Hypofractionated Stereotactic Irradiation

Nivolumab intravenously (IV): 240 mg every (q) 3 weeks x 4 months followed by 480 mg X 4 months.

Bevacizumab intervenously (IV): 15 mg/kg every (q) 3 weeks when given with Ipilumumab and Nivolumab combination. Dose changed to 10mg/kg every 2 weeks when given with Nivolumab only.

Ipilimumab 1mg/kg intervenously (IV) 200 mg (5 mg/mL) every (q) 3 weeks for 4 months.

Solmaz Sahebjam, M.D.

The main purpose of this study is to evaluate the safety, and tolerability of nivolumab, ipilimumab, and bevacizumab given in combination with hypofractionated stereotactic re-irradiation of recurrent high grade gliomas.

Hypofractionated Stereotactic Irradiation With Nivolumab, Ipilimumab and Bevacizumab in Patients With Recurrent High Grade Gliomas

Phase I Trial of Hypofractionated Stereotactic Irradiation (HFSRT) Combined With Nivolumab, Ipilimumab and Bevacizumab in Patients With Recurrent High Grade Gliomas

Safety and tolerability of nivolumab, given in combination with hypofractionated stereotactic re-irradiation of recurrent high grade gliomas.

All participants will receive efficacy assessments with brain MRI at time points specified in Trial Flow Chart. Cases of suspected radiologic disease progression will be confirmed by an MRI performed approximately 8 weeks after the initial radiological assessment of progression. Immunotherapy Response Assessment in Neuro-Oncology (iRANO) and Response Assessment Criteria for High-Grade Gliomas (RANO Criteria) will be used for assessing the response to study treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Implantable Microdevice In Primary Brain Tumors	NCT04135807	Grade II Glioma Grade III Gliom... Grade IV Glioma Astrocytoma Oligodendroglio... Anaplastic Astr... Anaplastic Olig... Glioblastoma	Microdevice	18 Years -	Dana-Farber Cancer Institute
Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma	NCT02858895	Glioblastoma Grade IV Astroc... Glioblastoma Mu... Grade IV Glioma	MDNA55	18 Years -	Medicenna Therapeutics, Inc.
Study To Test the Safety and Efficacy of TVI-Brain-1 As A Treatment for Recurrent Grade IV Glioma	NCT01290692	Grade IV Glioma Grade IV Astroc... Glioblastoma Mu...	TVI-Brain-1	18 Years -	TVAX Biomedical
Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma	NCT02858895	Glioblastoma Grade IV Astroc... Glioblastoma Mu... Grade IV Glioma	MDNA55	18 Years -	Medicenna Therapeutics, Inc.
A Study of the Safety and Efficacy of Tarceva in Patients With First Relapse of Grade IV Glioma (Glioblastoma Multiforme)	NCT00337883	Glioblastoma	Erlotinib HCl (...	18 Years -	Genentech, Inc.
A Study of the Safety and Efficacy of Tarceva in Patients With First Relapse of Grade IV Glioma (Glioblastoma Multiforme)	NCT00337883	Glioblastoma	Erlotinib HCl (...	18 Years -	Genentech, Inc.
Hypofractionated Stereotactic Irradiation With Nivolumab, Ipilimumab and Bevacizumab in Patients With Recurrent High Grade Gliomas	NCT02829931	Malignant Gliom...	Hypofractionate... Nivolumab Bevacizumab Ipilimumab	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Study To Test the Safety and Efficacy of TVI-Brain-1 As A Treatment for Recurrent Grade IV Glioma	NCT01290692	Grade IV Glioma Grade IV Astroc... Glioblastoma Mu...	TVI-Brain-1	18 Years -	TVAX Biomedical

Spots Global Cancer Trial Database for grade iv glioma