Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Sarcoma

Brain Neoplasms

Central Nervous System Neoplasms

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Meningioma

Nervous System Neoplasms

Ependymoma

Rhabdoid Tumor

Choroid Plexus Neoplasms

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Soft Tissue Sarcoma

Neuroepithelioma

Terri S Armstrong, C.R.N.P.

Background:

Primary tumors of the brain and spine are those that start in the brain or spine. These tumors are rare, accounting for \<2% of all cancers diagnosed in the United States. Some of these tumors occur in less than 2,000 people per year. Researchers want to study a large group of people with this kind of tumor. They want to learn more about the tumors, including the risk factors related to how they develop in adults.

Objective: To collect health and gene data to learn about what changes are associated with a rare CNS Tumors, to eventually screen for these changes or target the genes in treatment.

Eligibility: Adult participants (Bullet) 18 years of age who self- identify as being diagnosed with one of 12 rare CNS tumors, including: Atypical teratoid rhabdoid tumor (ATRT); Brainstem and midline gliomas; Choroid plexus tumors; Ependymoma; High grade meningioma; Gliomatosis cerebri; Medulloblastoma; Oligodendroglioma / Anaplastic oligodendroglioma; Pineal region tumors; Pleomorphic xanthroastrocytoma / Anaplastic pleomorphic xanthroastrocytoma; PNET (Supratentorial embryonal tumor); Primary CNS sarcoma / Secondary CNS sarcoma (Gliosarcoma).

Design: (Registered Trademark)Participants will be invited to participate through an ad on the CERN Foundation website (ependymoma), information on the Neuro-Oncology Branch website and other identified advocacy and social media sites and direct mailer to those who have already participated in the EO projects. (Registered Trademark)

* Interested participants will complete an enrollment form that will be sent to the study coordinator.
* The coordinator will then send the participant a consent form and schedule a time for phone consent.
* Participants will complete the Rare CNS tumors Outcomes Survey and once completed, the Rare CNS tumors Risk survey.

(Registered Trademark)

* The questions on the Outcomes Survey will include treatment history, symptoms social and clinical information and it should take about 25-35 minutes. The Risk survey will cover their demographic information, personal medical history, family medical history and environmental exposures. This should take about 52 minutes.
* Participants who have physical problems can have help with the surveys and forms.
* Once the surveys are completed, participants will be mailed a kit to collect saliva for germline DNA. Participants will ship the sample to the study team in a prepaid envelope
* If the sample is not sufficient, participants will be contacted to give provide an additional sample.

Background:

Rare cancers are defined as those with \<40,000 cases per year. There are over 130 separate types of primary CNS tumors, all of which meet the definition of a rare cancer. However, some CNS cancers have incidences of less than 1,000 cases per year. Because of its relative rarity, limited reports of the presentation and clinical course have been completed. With the support of the CERN-Foundation, the Adult Ependymoma Outcomes Projects (AEO) was launched to address this lack of information for one type of rare CNS tumor- ependymoma. Using an online platform, participants and families from across the world have participated, providing information that has helped elucidate the presentation and ongoing health of individuals with this disease. To date, over 300 adults have participated with over 95% reporting interest in continuing and expanding their participation. Results from the AEO baseline survey and a follow-up survey (AEOII addressing socioeconomic impact of the disease) have been published. The most recent data from the AEO has been presented at the Society for Neuro-Oncology (SNO) annual meetings in 2015 and 2016.

An additional consequence of the relative rarity of these CNS tumors, studies to evaluate risk factors for the occurrence of these rare CNS tumors or predicting the clinical course of these rare CNS tumors are also limited. Rare CNS tumors like other cancers, occur when there are changes to genes that control the way cells grow and divide often as a result of exposure to other environmental risk factors. Therefore, exploring genetic changes in persons with rare CNS tumors will allow us to begin to understand what changes are associated specifically with these tumors. To date, these participants are often included as part of larger cohorts which include other types of brain tumors. We now understand that even among gliomas, the risk factors differ. Therefore, identifying the risk factors specifically associated with rare CNS tumors is critical for primary prevention and early detection. This knowledge would allow scientists and physicians to eventually screen for these changes or target the genes or the processes they control for treatment purposes.

Objectives:

The primary objectives of this study are to:

* Obtain self-reported data on treatment, symptoms, functional status, and quality of life for adult participants with rare CNS tumors.
* To evaluate the relationship between health status and disease and treatment characteristics.
* To evaluate self-reported clinical and demographic risk factors in adult participants in the rare CNS tumor participant population.
* To explore genomic susceptibility in participants with rare CNS tumors

Eligibility:

The adult rare CNS tumor population for this study are participants \>= 18 years of age who self- identify as being diagnosed with one of 12 rare CNS tumors, including:

* Atypical teratoid rhabdoid tumor (ATRT)
* Brainstem and midline gliomas
* Choroid plexus tumors

  * Choroid plexus carcinoma
  * Choroid plexus papilloma
  * Atypical choroid plexus papilloma
* Ependymoma

  * Subependymoma
  * Myxopapillary ependymoma
  * Papillary ependymoma
  * Clear cell ependymoma
  * Tanycytic ependymoma
  * RELA fusion-positive
  * Anaplastic ependymoma
  * Posterior Fossa A
  * Posterior Fossa B
* High grade meningioma

  * Chordoid meningioma
  * Clear cell meningioma
  * Atypical meningioma
  * Papillary meningioma
  * Rhabdoid meningioma
  * Anaplastic (malignant) meningioma
* Gliomatosis cerebri
* Medulloblastoma

  * Sonic Hedge Hog (SHH)
  * WNT
  * Group 3
  * Group 4
* Oligodendroglioma / Anaplastic oligodendroglioma
* Pineal region Tumors

  * Pineoblastoma
  * Pineocytoma
  * Pineal parenchymal tumor of intermediate differentiation
  * Papillary tumor of the pineal region
* Pleomorphic xanthroastrocytoma / Anaplastic pleomorphic xanthroastrocytoma
* PNET (Supratentorial embryonal tumor)
* Primary CNS sarcoma / Secondary CNS sarcoma (Gliosarcoma)

Design:

* This study represents an ongoing effort to systematically evaluate outcomes in a large group of participants with these rare tumors. It will provide descriptive data which can be used to design further studies evaluating interventions related to identified health and quality of life related issues for this participant population.
* Participants will be invited to participate through an ad on the CERN Foundation website (ependymoma), information on the Neuro-Oncology Branch website and other identified advocacy and social media sites and direct mailer to those who have already participated in the EO projects.
* The goal of adding the Rare CNS tumors Risk Survey is to implement a survey to further evaluate participants in the EO for several known and suspected risk factors for rare CNS tumors and to obtain germline DNA to interrogate genomic susceptibility to the disease.
* Interested participants will complete an enrollment form that will be sent to the study coordinator. Once submitted, the study coordinator will then send the participant a consent form and schedule a time for remote consent if interested.
* Once consent is obtained, the study coordinator will send the participant instructions and a unique link that they will use to access and complete the survey(s).
* Once the surveys are completed, the study coordinator will email the participant a request for medical records to help us collect more health information related to care for their Rare CNS tumor diagnosis.
* Once the survey(s) are completed, the participant will be mailed a kit to collect saliva for germline DNA.

Rare CNS Tumors Outcomes &Risk

Exploring Outcomes and Risk in Patients With Rare Central Nervous System Tumors

.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Obtain self-reported data on treatment, symptoms, functional status, and quality of life for adult participants with rare CNS tumors To evaluate the relationship between health status and disease and treatment characteristics. To evaluate self-reported clinical and demographic risk factors in adult participants in the rare CNS tumors participant population. To explore genomic susceptibility in participants with rare CNS tumors.

National Cancer Institute (NCI)

Symptoms and General Pathology

Recurrence

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* Pembrolizumab will be administered every 3 weeks
* Pembrolizumab will be administered through IV infusion

pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells

Priscilla Brastianos, MD

This research study is studying a drug as a possible treatment for High Grade Meningioma.

The drug involved in this study is an immunotherapy drug called pembrolizumab

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this specific disease but it has been approved for other uses.

In this research study, the investigators are studying pembrolizumab in participants with meningioma. Research studies have shown that meningioma tumor cells express a gene called PD-L1. The investigators will be looking to determine whether the study drug may may stop meningioma tumors from growing.

Phase II Trial of Pembrolizumab in Recurrent or Residual High Grade Meningioma

Progression-free survival at 6 months is defined as not having disease progression per RANO (response assessment in neuro-oncology) criteria or death from any cause within six months of the first day of treatment with pembrolizumab.

Contrast-enhanced cranial magnetic resonance imaging (MRI) was performed every 6 weeks to assess patient response to treatment. Progressive disease is defined per RANO criteria as the appearance of a new lesion, an increase in the size of a patient's existing lesions, or clear clinical worsening (seizures, medication side effects, complications of therapy, cerebrovascular events, infection, etc.)

OS is defined as the time from protocol registration until death due to any cause. The follow-up of patients who were alive at the time of analysis was censored at the date of last assessment of vital status. 90% confidence intervals for median OS were estimated using log(-log(survival)) methodology.

OS benchmarked at 3 months measures the percentage of participants who are still alive at 3 months, after study registration and receiving study therapy.

OS benchmarked at 6 months measures the percentage of participants who are still alive at 6 months, after study registration and receiving study therapy.

All adverse events (AEs) recorded during the trial were summarized for all patients who received one or more doses of pembrolizumab. This outcome measure includes adverse events assessed as at least possibly related to study therapy and grade 3 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.

Intracranial response is defined as complete response (CR), partial response (PR), or stable disease (SD) by RANO (response assessment for neuro-oncology) criteria. Intracranial response was assessed by contrast-enhanced cranial magnetic resonance imaging (MRI) every 6 weeks.

CR: complete disappearance of all enhancing measurable and non-measurable disease sustained for 4+ weeks, no new lesions, stable/decreasing corticosteroids, and patient is stable and improved clinically. Participants with non-measurable disease cannot have a CR; the best possible response is SD.

PR: greater than or equal to 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for 4+ weeks, no progression of non-measurable disease, no new lesions, stable/decreasing corticosteroids, and patient is stable or improved clinically.

SD: does not qualify for CR, PR, or disease progression and patient is stable clinically.

Merck Sharp & Dohme LLC

Massachusetts General Hospital

Principal Investigator

In addition to the clinicaltrials.gov seriousness criteria, the following seriousness criteria are added: (1) new cancer (that is not a condition of the study) and (2) associated with an overdose.

* Pembrolizumab will be administered every 3 weeks
* Pembrolizumab will be administered through IV infusion

Pembrolizumab: pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rare CNS Tumors Outcomes &Risk	NCT03251989	High Grade Meni... Ependymoma Medulloblastoma PNET Primary CNS Sar...		18 Years -	National Institutes of Health Clinical Center (CC)
Rare CNS Tumors Outcomes &Risk	NCT03251989	High Grade Meni... Ependymoma Medulloblastoma PNET Primary CNS Sar...		18 Years -	National Institutes of Health Clinical Center (CC)
Phase II Trial of Pembrolizumab in Recurrent or Residual High Grade Meningioma	NCT03279692	High Grade Meni...	Pembrolizumab	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for high grade meningioma