Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Carcinoma

Papilloma

Papilloma, Choroid Plexus

Choroid Plexus Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Cerebral Ventricle Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Choroid Plexus Carcinoma

Choroid Plexus Papilloma

Antineoplastic Agents

All Drugs and Chemicals

Fibrinolytic Agents

Anticoagulants

Carboplatin

Topotecan

Melphalan

Heparin

Calcium heparin

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Subjects are pre-treated with heparin, and then given single doses of Melphalan, Carboplatin, and Topotecan consecutively via intra-arterial infusion. Multiple arteries may be used, with the total dose of the drugs remaining the same.

Mark Souweidane, M.D.

Colleen Sanders

Colleen Sanders, RN

Mark Souweidane, MD

This study will test the safety and efficacy of intra-arterial chemotherapy in subjects with newly diagnosed, residual, or recurrent atypical choroid plexus papilloma and choroid plexus carcinoma prior to a second surgery.

It is believed that intra-arterial chemotherapy will be safe and feasible for this population and will result in decreased tumor size, which may further improve the goals of a second-look surgery.

The intent of this study is to determine if intra-arterial chemotherapy is a safe and effective option for subjects with atypical choroid plexus papilloma and choroid plexus carcinoma prior to receiving second-look surgery. Angiography occurs when a catheter is inserted through the subjects vasculature to the major vessels that supply cerebral circulation. Subjects on this trial will undergo a a cerebral angiogram to determine the ideal arteries to use for drug infusion. Once identified, chemotherapy will be delivered through the catheter directly to the site of tumor.

Intra-Arterial Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma and Choroid Plexus Carcinoma Prior to Second-Look Surgery

Intra-Arterial (IA) Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma (ACPP) and Choroid Plexus Carcinoma (CPC) Prior to Second-Look Surgery

Determined by comparison of pathology reports and surgical outcomes

Weill Medical College of Cornell University

Glioma

Spinal Cord Neoplasms

Pinealoma

Brain Stem Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Spinal Cord Diseases

Pineocytoma

Brain Tumor, Childhood

Pineoblastoma

Neuroepithelioma

Anti-Infective Agents

Central Nervous System Depressants

Pharmaceutical Solutions

Other Dietary Supplements

Ethanol

Perillyl alcohol

Glycerol

Perillyl Alcohol

Patients will receive IN NEO100 that will follow a dose titration design, followed by a standard dose escalation design to establish safety. Brain tumor delivery of NEO100 will be confirmed in each disease sub-type by surgical resection/needle biopsy only if clinically indicated and scheduled for clinical purposes and testing with residual tissue for NEO100 and the major metabolite of NEO100 (Perillic Acid).

The study will use a modified Fibonacci dose titration design, followed by a standard dose escalation design.

* Cohort 1: 192 mg NEO100, QID on a 28-day cycle
* Cohort 2: 288 mg NEO100, QID on a 28-day cycle
* Cohort 3: 384 mg NEO100, TID on a 28-day cycle;
* Cohort 4 (ceiling dose): 576 mg NEO100, BID on a 28-day cycle.

Patients undergoing surgical or needle biopsy (only when clinically indicated) will receive a minimum of four days IN NEO100 treatment prior to the procedure.

NEO100 is a purified form (\>98.5%) of the naturally occurring monoterpene perillyl alcohol.

NEO100 drug product is a non-sterile solution for intranasal administration. It is compounded as a 10% solution in a 50:50 mixture of ethanol:glycerol.

NEO100

Chris Beardmore

Chloe Richmond

This is an open label, Phase 1b safety, dose-finding, brain tumor delivery, and pharmacokinetics study of intranasal NEO100 in patients with pediatric-type diffuse high grade gliomas. Patients will receive IN NEO100 that will follow a dose titration design, followed by a standard dose escalation design to establish safety. Brain tumor delivery of NEO100 will be confirmed in each disease sub-type by surgical resection/needle biopsy only if clinically indicated and scheduled for clinical purposes and testing with residual tissue for NEO100 and the major metabolite of NEO100 (Perillic Acid).

NEO100 drug product is a non-sterile solution for intranasal administration.

A feature of the clinical trials of NEO100 is to investigate the efficacy of this drug when it is delivered intranasally. Based on the general body of data on intranasal drug delivery, as well as the promising results from clinical studies in which perillyl alcohol was delivered intranasally, NeOnc expects that intranasal administration of NEO100 will allow rapid and more selective delivery of therapeutic levels of the drug to the brain, while minimizing systemic toxicity and first pass metabolism.

The study is a dose titration 1+1 design with a modified Fibonacci dose escalation, followed by a expansion design, used to determine the maximum tolerated dose and to select a recommended Phase 2 dose (RP2D). The starting dose of 192 mg mg/dose administered QID, on a 28-day cycle, is one dose below the safe dose administered to adults in a Phase 1/2a study. Dosing will increase using a modified Fibonacci dose escalation. The daily dose will start at 768 mg/day, and rise to 1,152 mg/day, which is also the safe dose administered to adults in a Phase 1/2a study.

The study is open to patient with Pediatric-type high grade glioma: Newly diagnosed and recurrent Diffuse Midline Glioma, H3 K27-altered; Diffuse hemispheric glioma, H3 G34-mutant, grade III and IV diffuse pediatric-type HGG, H3-wildtype and IDH-wildtype (including spinal cord tumors); Recurrent malignant tumors involving the brainstem or posterior fossa (choroid plexus carcinoma, CNS embryonal tumors, and pineoblastoma).

A Study of the Safety, Dosing, and Delivery of NEO100 in Patients With Pediatric Brain Tumors

An Open Label, Phase 1b Safety, Dose-finding, Brain Tumor Delivery, and Pharmacokinetics Study of Intranasal NEO100 in Patients With Pediatric-type Select Brain Tumors

Assess the safety and tolerability of increasing dose levels of intranasally administered NEO100 using the NCI CTCAE (version 5.0) for reporting of non-hematologic AEs

Assess the maximum tolerated dose (MTD) of intranasally administered NEO100 using the NCI CTCAE (version 5.0) for reporting of non-hematologic AEs

Confirm brain tumor delivery by measuring levels of NEO100 (POH) and its metabolite perillic acid (PA) in postsurgical tumor tissue in patients with pediatric-type brain tumors (measured in ng/mg).

To confirm blood brain barrier (BBB) penetration of NEO100 by measuring the concentration of NEO100 and its metabolite in resected tumor tissue.

Pharmacokinetic parameters of NEO100 metabolite perillic acid in the resected tumor tissue as measured by peak plasma concentration (Cmax).

Pharmacokinetic parameters of NEO100 metabolite perillic acid in the resected tumor tissue as measured by the time to peak plasma concentration (Tmax).

Pharmacokinetic parameters of NEO100 metabolite perillic acid in the resected tumor tissue as measured by the area under the plasma concentration vs time curve (AUC).

Objective CNS tumor response to NEO100 as determined by RANO 2.0 criteria.

Neonc Technologies, Inc.

Infections

Skin and Connective Tissue Diseases

Glioblastoma

Astrocytoma

Oligodendroglioma

Herpes Simplex

Virus Diseases

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Ependymoma

Rhabdoid Tumor

Gliosarcoma

Supratentorial Neoplasms

Germ Cells Tumors

Anaplastic Astrocytoma

Immunomodulating Agents

Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI. If G207 is safe in the first two cohorts of patients, subsequent patients will receive a single dose of G207 infused through catheters into region(s) of tumor defined by MRI followed by a 5 Gy dose of radiation to the tumor given with 24 hours of virus inoculation.

Intervention: Biological: G207

Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI

G207

Gregory K Friedman, M.D.

This study is a clinical trial to determine the safety of injecting G207 (a new experimental virus therapy) into a recurrent or progressive brain tumor. The safety of combining G207 with a single low dose of radiation, designed to enhance virus replication and tumor cell killing, will also be tested.

Outcomes for children with recurrent or progressive supratentorial malignant brain tumors are very poor, and there are a lack of effective salvage therapies once a patient fails standard treatments.

G207 is an oncolytic herpes simplex virus-1 (HSV) that has been successfully engineered to introduce mutations in the virus that enable it to selectively replicate in and kill cancer cells, but not normal cells. Replication of G207 in the tumor 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 engenders an anti-tumor immune response; the virus is immunogenic and produces a debris field which exposes cancer cell antigens to immune cells which can target other cancer cells. Thus, the oncolytic effect of the virus and the immune response that the virus stimulates provide a one-two punch at attacking cancer cells. In preclinical studies, a single 5 Gy dose of radiation within 24 hours of virus inoculation to the tumor increased virus replication and tumor cell killing.

The University of Alabama at Birmingham has conducted three phase I trials of G207 injected into the recurrent tumor alone or combined with a single dose of radiation in adults with recurrent high-grade gliomas. In these trials, high doses (up to 3 x 10\^9 plaque-forming units) of virus were safely injected directly into the tumor or surrounding brain tissue without serious toxicities. A maximum tolerated dose was not reached in all 3 trials. Radiographic and neuropathologic evidence of an antitumor response was seen in some patients. Preclinical laboratory studies have demonstrated that a variety of aggressive pediatric brain tumor types are sensitive to G207.

This study is a phase I, open-label, single institution clinical trial of G207 alone or combined with a single low dose of radiation in children with recurrent or progressive supratentorial brain tumors. The primary goal is to determine safety. The secondary aims are to obtain preliminary information on the effectiveness of and immune response to G207.

A traditional 3 + 3 design will be used with four patient cohorts. The first two cohorts will receive G207 at one of two doses, and the second two cohorts will receive G207 at one of two doses followed by a 5 Gy dose of radiation.

HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors

Phase I Clinical Trial of HSV G207 Alone or With a Single Radiation Dose in Children With Recurrent Supratentorial Brain Tumors

All events with a Grade 3 or above toxicity (defined by the CTCAE v4.0) will be tabulated by event and by relationship to G207.

HSV-1 antibody titers will be checked by ELISA prior to the administration of G207 and at regular intervals after treatment.

Saliva, blood and conjunctival secretions will be checked by polymerase chain reaction (PCR) and culture at regular intervals for evidence of HSV shedding and/or viremia.

Time after G207 administration to clinical and radiographic disease progression will be evaluated.

The overall survival for each patient receiving G207 will be calculated.

A modified Lansky score (for children under 16 years of age) or Karnofsky score (for children 16 and older) will be recorded and measured serially with the pre-treatment score.

Quality of life will be measured with questionnaires taken at baseline (before administration of G207) and at specified times thereafter.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intra-Arterial Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma and Choroid Plexus Carcinoma Prior to Second-Look Surgery	NCT04994977	Atypical Choroi... Choroid Plexus ...	Melphalan Carboplatin Topotecan	0 Years - 100 Years	Weill Medical College of Cornell University
A Study of the Safety, Dosing, and Delivery of NEO100 in Patients With Pediatric Brain Tumors	NCT06357377	Pediatric Tumor... Pediatric Tumor... Diffuse Midline... Pediatric Tumor... Pineocytoma Choroid Plexus ... Spinal Cord Tum... High Grade Glio...	NEO100	5 Years - 18 Years	Neonc Technologies, Inc.
HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors	NCT02457845	Supratentorial ... Malignant Gliom... Glioblastoma Anaplastic Astr... PNET Cerebral Primit... Embryonal Tumor	G207	3 Years - 18 Years	University of Alabama at Birmingham

Spots Global Cancer Trial Database for choroid plexus carcinoma