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

Disease Attributes

Immunomodulating Agents

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

NEOADJUVANT: Patients receive nivolumab IV over 30 minutes 14 days before undergoing standard of care surgical resection.

ADJUVANT MAINTENANCE: After completion of neoadjuvant infusion, patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ancillary studies, given in person or online

Quality-of-Life Assessment

Questionnaire Administration

Jannerfer An

Sabine Mueller, MD, PhD

Girish Dhall, MD

Katie Metrock, MD

Tom Davidson, MD

Megan Paul, MD

Sabine Mueller, MD, Phd

Sabine Mueller, MD

Lindsay Kilburn, MD

Elias Sayour, MD, PhD

Scott Coven, DO, MPH

Runco Daniel, MD, MS

Kenneth Cohen, MD, MBA

Eric Raabe, MD

Susan Chi, MD

Mohamed Abdelbaki, MD

Derek Hanson, MD

Linda Stork, MD

Matthew Miller, MD

Nicholas Whipple, MD

Priya Chan

David Ziegler, BSc (Med), MBBS, FRACP, MD/PhD

Regienald Gayaman

Dinisha Govender, MBChB, FRACP

Natasha Brown

Karen Clements

Tim Hassall, MBBS, FRACP

Callie Ayles

James Kirby

Maria Kirby, MBBS FRACP

Yun Y Tu

Kanika Bhatia, MD

Nick Gottardo, MB,ChB,FRACP,PhD

Michal Yalon

Nicolas Gerber, MD

Tom Davidson (tdavidson@chla.usc.edu), MD

This phase I trial studies the side effects of nivolumab before and after surgery in treating children and young adults with high grade glioma that has come back (recurrent) or is increasing in scope or severity (progressive). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To measure the relative changes in cell cycle-related genetic signature of the tumor microenvironment post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG when compared to a cohort of archived non-treated recurrent pediatric HGG samples.

II. To characterize the safety and tolerability of neoadjuvant nivolumab followed by adjuvant nivolumab in children and young adults with recurrent or progressive HGG.

SECONDARY OBJECTIVES:

I. To determine the 6 month and 12 month overall survival (OS) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

II. To determine the 6 month and 12 month progression-free survival (PFS) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

EXPLORATORY OBJECTIVES:

I. To measure relative changes in interferon gamma associated genetic signature within the tumor microenvironment post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG compared to archived non-treated recurrent pediatric HGG samples.

II. To explore the correlation of interferon-gamma-associated genetic signature, cell cycle-related genetic signature and infiltrating T lymphocyte (TIL) density and clonality with clinical responses.

III. To measure TIL density post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG.

IV. To estimate the objective response rate (ORR) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

V. To evaluate the association between advanced MRI parameters (ADC on DWI, rCBV on dynamic susceptibility contrast (DSC) perfusion MRI, pre-contrast T1 shortening on T1-weighed images, and/or MTRasym on pH-Weighted Amine CEST-EPI) and tumor and peripheral blood immune responses.

VI. To measure relative change in peripheral T-cell response and post administration of neo-adjuvant nivolumab in children and young adults with recurrent or progressive HGG.

VII. To measure PD-1 and PDL-1 expression by immunohistochemistry for children and young adults with recurrent or progressive HGG post neoadjuvant nivolumab and evaluate the differences between the treatment cohort and archived non-treated recurrent pediatric HGG samples.

VIII. To explore the correlation of tumor mutational load with clinical response for children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

IX. To assess Quality of Life (QOL) and cognitive measures in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

X. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks.

XI. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks.

OUTLINE: Neoadjuvant nivolumab followed by adjuvant nivolumab evaluation.

NEOADJUVANT TREATMENT: Participants will receive a single infusion of nivolumab of 3 mg/kg 14± 5 days prior to surgery. When scheduling, please keep in mind that the two pre-surgical plasma samples (day of neoadjuvant dose and day of surgery) should be drawn greater than 10 days apart.

Tumor samples will be obtained at time of surgery. The tissue from this surgery (fresh, frozen and FFPE) and the archived tissue (FFPE) from the most recent surgery prior to registration revealing HGG will be processed so as to best achieve the primary, secondary and exploratory objectives.

ADJUVANT TREATMENT: Infusion Cycle #1 should begin as soon as participant has recovered from surgery and has been tapered off of steroids. A maximum dexamethasone dose of 0.1 mg/kg/day is allowed, but preferably have been discontinued (inhaled or topical use of steroids is allowed).

Maintenance Cycle 1+ Day 1 \& 15: Participants will receive nivolumab (3mg/kg) IV every 2 weeks until progression or development of unacceptable toxicities or withdrawal. Blood samples will be obtained as pharmacodynamic markers throughout the study (Day 1 of every other cycle). Dose interruptions and symptomatic management will occur based upon preset adverse event determination.

After completion of study treatment, patients are followed up at 30 days and then every 2 months for up to 5 years.

Immunotherapy Before and After Surgery for Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults

A Single Arm, Pilot of Neoadjuvant Checkpoint Inhibition Followed by Adjuvant Checkpoint Inhibition in Children and Young Adults With Recurrent or Progressive High Grade Glioma (HGG)

Will assess the percentage change in cell cycle-related genetic signature post administration of neoadjuvant treatments when compared to archived recurrent pediatric HGG group. The number of participants with high cell cycle gene signature (positive median gene set variation analysis (GSVA) score) will be tabulated. Variables involved in the primary analyses will be examined graphically and summarized by descriptive statistics.

Adverse events will be monitored throughout the trial and graded in severity according to the guidelines outlined in the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 from initiation of study treatment until 2 years after treatment discontinuation or until study treatment related adverse events resolve or return to baseline, Adverse experiences (specific terms as well as system organ class terms) and predefined limits of change in laboratory, and vital sign parameters that are not pre-specified as events of interest will be summarized with descriptive statistics (counts, percentage, mean, standard deviation, etc.).

Survival will be assessed at 6 months and 12 months from the time of enrollment until the time of death. Kaplan-Meier survival analyses will be performed. Medians together with 2-sided 95% confidence intervals will be computed using a log-log transformation.

PFS is defined as the time of enrollment until the time of progressive disease or death. Kaplan-Meier survival analyses will be performed. Medians together with 2-sided 95% confidence intervals will be computed using a log-log transformation.

Pacific Pediatric Neuro-Oncology Consortium

Principal Investigator

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Anti-Infective Agents

Fluorouracil

Flucytosine

Clotrimazole

Miconazole

Antifungal Agents

Antimetabolites

All patients will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene. CD converts the antifungal 5-FC to the anti-cancer drug 5-FU in cells that have been infected by the Toca 511 vector. Beginning approximately 6 weeks after administration of Toca 511, patients will begin courses of oral Toca FC at pre-specified intervals, depending on cohort, during the approximately 30 week study.

Toca 511 vector

Toca FC

Asha Das, MD

Timothy Cloughesy, MD, NO

This is a multicenter study evaluating the safety and tolerability of increasing doses of Toca 511, a retroviral replicating vector, injected into the resection cavity of patients with Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Approximately 6 weeks after injection of Toca 511, patients will begin an oral courses of Toca FC, an antifungal agent. These one week courses of Toca FC will be repeated during the approximately 30 week study. Two separate cohorts of patients treated with Toca 511 and Toca FC will also be evaluated with either of the following standard treatments for glioma: lomustine or bevacizumab. After completion of this study, all patients will be eligible for enrollment and encouraged to enter a long-term continuation protocol that enables additional Toca FC treatment cycles to be given, as well as permits the collection of long-term safety and survival data.

Study of a Retroviral Replicating Vector Combined With a Prodrug to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor

A Phase 1 Ascending Dose Trial of Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered to Subjects at the Time of Resection for Recurrent High Grade Glioma & Followed by Treatment With Toca FC, Extended-Release 5-FC

Excluding nausea, vomiting and fatigue, any Grade 3 or higher non-hematologic toxicity or any Grade 4 or higher hematologic toxicity, felt to be related to Toca 511 or the Toca 511/Toca FC combination.

Tocagen Inc.

Bevacizumab

Ipilimumab

Angiogenesis Inhibitors

Growth 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.

OS, utilizing 95% confidence interval (95%CI).

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
Immunotherapy Before and After Surgery for Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults	NCT04323046	Glioblastoma Malignant Gliom... Recurrent Gliob... Recurrent Malig... Recurrent Grade... Grade III Gliom...	Nivolumab Quality-of-Life... Questionnaire A...	6 Months - 25 Years	University of California, San Francisco
Study of a Retroviral Replicating Vector Combined With a Prodrug to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor	NCT01470794	Glioblastoma Mu... Anaplastic Astr... Anaplastic Olig... Anaplastic Olig...	Toca 511 vector Toca FC	18 Years - 80 Years	Tocagen 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

Spots Global Cancer Trial Database for grade iii glioma