Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Recurrence

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Subjects with HER2 staining of Grade 3 (51-100% of cells staining for HER2) and intensity scores of 3+ will be assigned to the High Risk arm. Three cell dosing schedules (1, 2, 3) consisting of combinations of three cell doses (A, B, C) will be evaluated.

All other patients not meeting the high risk description will be assigned to the Standard Risk arm. Three cell dosing schedules (1, 2, 3) consisting of combinations of three cell doses (A, B, C) will be evaluated.

Dosing Schedule 1:

Cycle 1 A: 1x10\^7 cells

Cycle 2 A: 1x10\^7 cells

Cycle 3 A: 1x10\^7 cells

Dosing Schedule 2:

Cycle 1 A: 1x10\^7 cells

Cycle 2 B: 3x10\^7 cells

Cycle 3 B: 3x10\^7 cells

Dosing Schedule 3:

Cycle 1 A: 1x10\^7 cells

Cycle 2 B: 3x10\^7 cells

Cycle 3 C: 1x10\^8 cells

Subsequent cycles\*

\*Additional cycles may be administered at ≤ the final cell dose reached in cycle 3, provided that the subject continues to meet eligibility criteria and does not have confirmed progressive disease.

HER2-specific T cells

Nabil M Ahmed, MD

Shoba Navai, MD

Meenakshi Hegde, MD

This study is for patients that have brain cancer. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting immune cells present in the blood that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients.

The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor 2). This antibody sticks to tumor cells because of a substance on the outside of these cells called HER2. Many types of brain tumors are positive for HER2 . HER2 antibodies have been used to treat people with HER2-positive cancers. For this study, the HER2 antibody has been changed so that instead of floating free in the blood it is now attached to T cells. When an antibody is joined to a T cell in this way it is called a chimeric antigen receptor (CAR). These CAR-T cells seem to be able to kill tumors like the one these patients have, but they don't last very long and so their chances of fighting the cancer are limited. Therefore, developing ways to prolong the life of these T cells should help them fight cancer.

These HER2-CAR T cells are an investigational product not approved by the Food and Drug Administration.

The purpose of this study is to find the largest safe dose of HER2-CAR T cells, to learn what the side effects are, and to see whether this experimental intervention might help patients with brain tumors who volunteer to test this new agent.

First, to find out if HER2 is expressed in the patient's brain cancer, the investigators will need to obtain the tissue block or tissue specimen that was used to make the original diagnosis. If there is enough material, investigators may also look for other proteins that may be targets for this sort of immune therapy in the future. Up to 90mls (18 tsp) of blood will be drawn on two occasions for a total of 180mls (36tsp). The total amount of blood drawn will not be more than 3 ml (less than 1 teaspoon) per 2.2 lbs of body weight.

To make HER2 CAR T cells the investigators will introduce the HER2 CAR gene into patient's T cells. To get the HER2 antibody to attach to the surface of the T cells, investigators will insert the antibody gene into the T cells. This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps the investigators find the T cells in patient's blood after they inject them. Most of the cells generated will be frozen and stored to give back to the patient.

This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dosing schedule (1 of 3 different levels) of T cells. Once that dose schedule proves safe, the next group of patients will be started at a higher schedule. This process will continue until all 3 dose schedules are studied. If the side effects are too severe, the dose will be lowered or the T-cell infusions will be stopped.

The patient will be given three injections of cells two weeks apart into a special catheter that a neurosurgeon will implant into the tumor or the cavity left in the brain after surgical removal or into the fluid-filled space in your brain. The first injection of cells you receive will be the lowest dose. The subsequent injections, depending on the patient's assigned dosing schedule, may be higher than the first. Before the patient receives each injection, they may be given a dose of Tylenol. Each injection will take between 1 and 10 minutes. The patient will be admitted for overnight observation after each T-cell injection. Injections of T cells will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.

If the patient has stable disease (the tumor did not grow), a reduction in the size of the tumor on imaging studies, or unconfirmed progressive disease, but health status is stable after the start of T-cell injections (at least 6 weeks after), they can receive additional doses of the T cells at 2 to 4 week intervals if they wish. Additional doses of T cells will be given at the highest cell dose the patient receives during the initial three cell infusions. Therefore, the dose the patient receives for additional doses may be higher than the initial dose they received.

Before being treated, the patient will receive a series of standard medical tests: physical exam, blood tests to measure blood cells, kidney and liver function,' pregnancy test if the patient is a female who could potentially become pregnant or might be pregnant, measurements of patient's tumor by routine imaging studies.

The patient will receive standard medical tests when they are getting the infusions and after: physical exams, blood tests to measure blood cells, kidney and liver function, measurements of patient's tumor by routine imaging studies 6 weeks after the infusion.

To learn more about the way the HER2-CAR T cells are working and how long they last in the body, an extra amount of blood, based on patient's weight, up to a maximum of 60 mL (12 teaspoons) of blood will be taken on the day of the T-cell infusion (before and 1 to 4 hours after the T-cell infusion), 3-4 days after the infusion (this one is optional), 1, 2, 4 and 6 weeks after the T-cell infusion and every 3 months for 1 year, every 6 months for 4 years, then yearly for a total of 15 years. This volume is considered safe, but may be decreased if the patient is anemic. This sample will be kept in a coded manner so that only the study staff may identify the patient.

During the time points listed above, if the T cells are found in patient's blood at a certain amount, an extra 5ml of blood may need to be collected for additional testing.

To see if there are any long-term side effects of gene transfer, the investigators will follow the patient up to 15 years.

If the patient receives additional T-cell infusions after the first one, s/he will have the same tests and blood draws as described above.

If the patient has a tumor biopsy or lumbar puncture to obtain CSF performed any time while s/he are on the study, a sample of this will be requested for research purposes.

If the patient develops a second abnormal growth, significant blood or nervous system disorder during the trial, a biopsy sample of the tissue will be tested for research purposes (if a sample can be obtained).

T Cells Expressing HER2-specific Chimeric Antigen Receptors(CAR) for Patients With HER2-Positive CNS Tumors

Phase I Study of Intracranial Injection of T Cells Expressing HER2-specific Chimeric Antigen Receptors (CAR) in Subjects With HER2-Positive Tumors of the Central Nervous System (iCAR)

To evaluate the safety of autologous T cells expressing transgenic chimeric antigen receptors (CAR) targeting the HER2 molecule administered into the tumor, tumor resection cavity, and/or cerebrospinal fluid (CSF) space of subjects with progressive recurrent or refractory HER2-positive primary central nervous system (CNS) tumor or HER2 positive tumor metastatic to the CNS, excluding diffuse intrapontine glioma (DIPG), after standard of care interventions.

To evaluate the effects of gene modified T cells on measurable disease.

Center for Cell and Gene Therapy, Baylor College of Medicine

The Methodist Hospital Research Institute

Baylor College of Medicine

Assistant Professor

All Drugs and Chemicals

ONO-7579

Protein Kinase Inhibitors

Enzyme Inhibitors

Drug Development Division

This study will determine the safety and maximum tolerated dose of ONO-7579 in patients with advanced solid tumors, and evaluate efficacy of ONO-7579 in patients with advanced solid tumors harboring NTRK gene fusions.

The trial was designed to be a Phase 1/2 trial, but was terminated without progressing to Phase 2.

Study of ONO-7579 in Patients With Advanced Solid Tumors/ NTRK Gene Fusion Positive Advanced Solid Tumors

An Open-label, Multi-center, Dose-escalation and Expansion Study to Evaluate the Safety and Efficacy of ONO-7579 in Patients With Advanced Solid Tumors/ NTRK Gene Fusion Positive Advanced Solid Tumors

To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD

Assessed by Independent Central Review using RECIST 1.1 or RANO criteria

Assessment of the maximum plasma concentration of ONO-7579

Assessment of the time to reach maximum observed plasma concentration of ONO-7579

Assessment of the plasma area under the curve from time zero to 24 hours after dosing

Assessment of the plasma decay half life of ONO-7579

Assessment of the trough concentration of ONO-7579 in plasma

Assessed by investigator using RECIST 1.1 or RANO criteria

To determine the safety and tolerability of ONO-7579

Ono Pharmaceutical Co. Ltd

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Glioma

Neuroblastoma

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neurofibroma, Plexiform

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroectodermal Tumors, Primitive, Peripheral

Nerve Sheath Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Neurofibromatosis

Neurofibromatosis Type 1

Optic Pathway Glioma

Neuroepithelioma

If 0 of 3-6 or no more than 1 of 6 evaluable participants experience a DLT, then the dose will be escalated to Dose Level 2 and the same approach will be repeated. If 2 or more DLTs are observed on Dose Level 1 in 2-6 subjects, then further enrollment to Dose Level 1 will stop, the dose will be de-escalated to Dose Level -1 and the same approach will be repeated. The MTD will be the highest dose with \<2 DLTs in 6 patients.

Participants will receive oral avutometinib once daily twice a week, three weeks on/ 1week off, for a period of 28 days per cycle

Avutometinib

Sameer Farouk Sait, MD

Julia Glade Bender, MD

Jason Fangusaro, MD

The purpose of this study is to find out whether avutometinib is a safe treatment for advanced or recurrent solid tumor cancers in children and young adults. Researchers will look for the highest dose of avutometinib that is safe and cause few or mild side effects.

A Study of Avutometinib for People With Solid Tumor Cancers

A Multi-Center Phase I Dose Escalation Study of Avutometinib, a RAF/MEK Clamp, in Pediatric Patients With Refractory or Recurrent Solid Tumors Harboring Activating MAPK Pathway Alterations

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary objective is to assess the safety of avutometinib in the pediatric population. CTCAE Version 5 will be utilized for toxicity evaluation. Adverse Events should be recorded from treatment start through 30 days after the last dose of study drug.

Memorial Sloan Kettering Cancer Center

Antineoplastic Agents

Bevacizumab

Fosbretabulin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Bevacizumab, CA4P

Ramin Altaha, MD

Pilot Trial of CA4P with Avastin in Recurrent Gliomas

The purpose of this study is to see if fosbretabulin, the drug being studied, combined with bevacizumab will help your brain cancer and if using these drugs together is safe.

OXC401-PO1s/WVU 1309 - A Pilot Study of Fosbretabulin With Bevacizumab in Recurrent High-Grade Gliomas

West Virginia University

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Breast Neoplasms

Thyroid Neoplasms

Thyroid Diseases

Sarcoma

Wilms Tumor

Thyroid Cancer, Papillary

Medulloblastoma

Sarcoma, Ewing

Fibrosarcoma

Nephroma, Mesoblastic

Soft Tissue Sarcoma

Wilms' Tumor

Papillary Thyroid Carcinoma

Ewing Sarcoma

Congenital Mesoblastic Nephroma

Amino Acids

Entrectinib

Tyrosine

Arm closed for further enrollment

ROS1, ALK non-gene fusion molecular alterations

Oral entrectinib (RXDX-101)

Arm closed for further enrollment

molecular alterations, including gene fusions

Oral entrectinib (RXDX-101)

Arm closed for further enrollment

Oral entrectinib (RXDX-101)

Arm closed for further enrollment

harboring - NTRK1/2/3, ROS1, ALK gene fusions

Oral entrectinib (RXDX-101)

Arm closed for further enrollment

Any participant who otherwise meet all other eligibility criteria

Oral entrectinib (RXDX-101)

gene fusions

Oral entrectinib (RXDX-101)

NTRK 1,2,3 and ROS1 fusions

Oral entrectinib (RXDX-101)

Clinical Trials

This is an open-label, Phase 1/2 multicenter dose escalation study in pediatric patients with relapsed or refractory extracranial solid tumors (Phase 1), with additional expansion cohorts (Phase 2) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 gene fusions, and extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions.

Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options

A Phase 1/2, Open-Label, Dose-Escalation And Expansion Study Of Entrectinib (Rxdx-101) In Pediatrics With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options

Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03)

AE, ECG and Labs assessed by NCI CTCAE v4.03

Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

Assessed by RECIST v1.1 per the BICR and investigator

Assessed by RANO per the BICR and investigator

Assessed by the Curie scale per the BICR and investigator

Assessed by RECIST v1.1 per the investigator

Hoffmann-La Roche

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Avelumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunologic Factors

Subjects will receive avelumab administered intravenously (IV) once every 2 weeks.

Subjects will receive avelumab at a recommended phase II dose (RP2D) adjudicated by a safety monitoring committee (SMC) from phase I part of the study.

Medical Responsible

This is a multi-center, open-label, international study to evaluate the dose, safety and tolerability, antitumor activity, pharmacokinetic and pharmacodynamics of avelumab in pediatric subjects 0 to less than 18 years of age with refractory or relapsed malignant solid tumors (including central nervous system tumors) and lymphoma for which no standard therapy is available or for which the subject is not eligible for the existing therapy.

The study was planned to be conducted in 2 parts: the dose-finding part (Phase I) and the tumor-specified expansion part (Phase II). However, Phase II was cancelled due to limited clinical benefit of PD-L1 monotherapy in pediatric participants.

Phase I/II Study of Avelumab in Pediatric Cancer Subjects

Open-label, Phase I/II Study to Evaluate Pharmacokinetics, Pharmacodynamics, Safety, and Anticancer Activity of Avelumab in Pediatric Subjects From Birth to Less Than 18 Years of Age With Refractory or Relapsed Solid Tumors and Lymphoma

Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Merck KGaA, Darmstadt, Germany

EMD Serono Research & Development Institute, Inc.

Osteosarcoma

Rhabdomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Immunomodulating Agents

Patients will undergo HLA-haploidentical bone marrow transplant preceded by reduced-intensity chemotherapy and radiation therapy, followed by donor NK cells on day +7 after transplant.

Allogeneic HCT

Donor NK Cell Infusion

Monica Thakar, MD

The investigators hypothesize that this Phase 2 cellular and adoptive immunotherapy study using human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) followed by an early, post-transplant infusion of donor natural killer (NK) cells on Day +7 will not only be well-tolerated in this heavily-treated population (safety), but will also provide a mechanism to treat high-risk solid tumors, leading to improved disease control rate (efficacy). Disease control rate is defined as the combination of complete (CR) and partial (PR) response and stable disease (SD). The investigators further propose that this infusion of donor NK cells will influence the development of particular NK and T cell subtypes which will provide immediate/long-term tumor surveillance, infectious monitoring, and durable engraftment.

Patients with high-risk solid tumors (Ewings Sarcoma, Neuroblastoma and Rhabdomyosarcoma) who have either measurable or unmeasurable disease and have met eligibility will be enrolled on this trial for a goal enrollment of 20 patients over 4 years.

Patients will receive a reduced-intensity conditioning regimen for 6 days that consists of Fludarabine 150 mg/m2, Cyclophosphamide 29 mg/kg, and 3 Gy total body irradiation (TBI), followed by HLA-haploidentical marrow from a family member on Day 0. On Days +3 and +4, Cyclophosphamide 50 mg/kg will be infused for selective in vivo T cell depletion. Additional post-grafting immune suppression will consist of mycophenolate mofetil and either tacrolimus or sirolimus.

Non-mobilized peripheral blood mononuclear cells will be collected from donors on Day +6, from which NK cells will be selected and infused into patients on Day +7.

Patients will be monitored for any transplant-related complications and will undergo disease monitoring every three months for the first two years post-transplant. Research studies will be conducted to follow the patient's immune status and quality of life post-transplant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
T Cells Expressing HER2-specific Chimeric Antigen Receptors(CAR) for Patients With HER2-Positive CNS Tumors	NCT02442297	Brain Tumor, Re... Brain Tumor, Re...	HER2-specific T...	3 Years -	Baylor College of Medicine
Study of ONO-7579 in Patients With Advanced Solid Tumors/ NTRK Gene Fusion Positive Advanced Solid Tumors	NCT03182257	Solid Tumor	ONO-7579	18 Years -	Ono Pharmaceutical Co. Ltd
A Study of Avutometinib for People With Solid Tumor Cancers	NCT06104488	Refractory Canc... CNS Tumors CNS Tumor, Adul... CNS Tumor, Chil... MAP Kinase Fami... NF1 Plexiform Neuro... Low-grade Gliom... Optic Pathway G... Neuroblastoma Primary Brain T... Solid Tumor Solid Tumor, Ad... Solid Carcinoma Central Nervous...	Avutometinib	3 Years - 30 Years	Memorial Sloan Kettering Cancer Center
OXC401-PO1s/WVU 1309 - A Pilot Study of Fosbretabulin With Bevacizumab in Recurrent High-Grade Gliomas	NCT01052363	Central Nervous...	Bevacizumab, CA...	18 Years -	West Virginia University
Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options	NCT02650401	Solid Tumors CNS Tumors	Entrectinib	0 Years - 18 Years	Hoffmann-La Roche
Phase I/II Study of Avelumab in Pediatric Cancer Subjects	NCT03451825	Refractory or R... Lymphoma	Avelumab Avelumab	0 Years - 18 Years	EMD Serono
OXC401-PO1s/WVU 1309 - A Pilot Study of Fosbretabulin With Bevacizumab in Recurrent High-Grade Gliomas	NCT01052363	Central Nervous...	Bevacizumab, CA...	18 Years -	West Virginia University
Phase 2 STIR Trial: Haploidentical Transplant and Donor Natural Killer Cells for Solid Tumors	NCT02100891	Ewing Sarcoma Neuroblastoma Rhabdomyosarcom... Osteosarcoma CNS Tumors	Allogeneic HCT Donor NK Cell I...	-	Medical College of Wisconsin
Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options	NCT02650401	Solid Tumors CNS Tumors	Entrectinib	0 Years - 18 Years	Hoffmann-La Roche
Study of ONO-7579 in Patients With Advanced Solid Tumors/ NTRK Gene Fusion Positive Advanced Solid Tumors	NCT03182257	Solid Tumor	ONO-7579	18 Years -	Ono Pharmaceutical Co. Ltd

Spots Global Cancer Trial Database for cns tumors

Every month we try and update this database with for cns tumors cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cns tumors

Every month we try and update this database with for cns tumors cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cns tumors cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.