Neoplasms

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

All Conditions

Ear, Nose, and Throat Diseases

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neurofibromatosis 2

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neuroma

Neuroma, Acoustic

Neurilemmoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Vestibulocochlear Nerve Diseases

Retrocochlear Diseases

Ear Diseases

Otorhinolaryngologic Diseases

Otorhinolaryngologic Neoplasms

Cranial Nerve Diseases

Neurofibromatosis

Neurofibromatosis Type 1

Neurofibromatosis Type 2

Schwannomatosis

Schwannoma

Neuroendocrine Tumor

Neuroepithelioma

Patients meeting clinical and/or genetic criteria for Neurofibromatosis 1

Patients meeting clinical and/or genetic criteria for Neurofibromatosis 2

Patients meeting clinical and/or genetic criteria for Schwannomatosis

Kate Kelts, B.S.N.

Annette Bakker, Ph.D.

The NF Registry is a database of patient-reported symptoms, treatments, and experiences with their neurofibromatosis disease. It is a contact registry to relay clinical trial opportunities to targeted patient subgroups, and to supply de-identified disease data to researchers. It has the potential to become a natural history resource.

Patients and parents of patients will be made aware of the Neurofibromatosis (NF) Registry through various non-commercial information sources such as the Children's Tumor Foundation (CTF) website, CTF-affiliated NF clinics, social media, CTF educational and fundraising events, and other nonprofit organizations and foundations such as the National Organization for Rare Diseases (NORD) and social media.

The NF Registry will be accessed by individual adult (over age 18) subjects via a web-based patient portal. The portal contains an IRB-approved informed consent form. Following consent, the registrant creates an account which is activated after email confirmation. An account can be created by an adult patient with the disorder, or by the parent or guardian of a child with the disorder. Account creators are required to enter identifiable contact and demographic data.

After the account is created, the account owner enrolls themselves or a minor family member (or both) and completes an on-line survey. There are separate surveys for NF1, NF2, and Schwannomatosis. The surveys ask about about the affected individual's medical and family history of the disease, testing and diagnosis, clinical manifestations (e.g., tumor types and locations) interventions and therapies, and quality of life. The account holder chooses whether to receive emails from the Registry with information about relevant clinical trials and studies for which they may be eligible.

Participant's responses are used to compile charts and graphics of de-identified aggregate data. Registered patients may view this data. Researchers may apply to our Data Use Committee for access to de-identified data or for subject recruitment emails to be sent to specific patient subgroups. Data capture and security for the NF Registry is done under contract by OpenApp (Dublin, Ireland), a web-based patient opt-in registry provider.Participants will be asked to update their information at least once a year. Their information will be stored in the NF Registry for an indefinite period of time. This longitudinal study is intended as a resource for patients and researchers. There is no specific outcome measure or anticipated endpoint.

Neurofibromatosis (NF) Registry Portal

Neurofibromatosis (NF) Registry Portal Funded by Children's Tumor Foundation

patients will input medical information and treatment information about their NF and update at least yearly in an ongoing natural history study

The Children's Tumor Foundation

Pain

Skin Neoplasms

Skin Diseases

All Drugs and Chemicals

Analgesics

Antibodies

Immunoglobulins

Mitogens

Tanezumab

Tanezumab 10 mg SC administered on day 1 and Day 57 (± 4 days)

Placebo SC (to match tanezumab SC) administered on Day 1 and tanezumab 10 mg SC on Day 57 (± 4 days)

Placebo

Scott R Plotkin

The primary objective of this study is to determine whether the administration of tanezumab, an anti-nerve growth factor (NGF) antibody, improves pain relief in schwannomatosis patients receiving background non-NSAID therapy.

Schwannomatosis is characterized by the predisposition to develop multiple schwannomas and, less commonly, meningiomas. Pain is the most frequent symptom reported by these patients, with 68% experiencing chronic pain.

The investigators propose to test the efficacy and tolerability of tanezumab as a treatment for schwannomatosis patients with chronic pain who have had inadequate pain relief in a randomized, placebo-controlled trial, which could form the basis of a larger, randomized controlled trial in the future.

The study is designed with a total duration of 281 days (40 weeks) and will consist of four periods: Pre-treatment, Double-Blind Treatment, Single Arm Treatment, and 24-Week Safety Follow-up. The Pre-Treatment Period lasting up to 30 days, followed by a Double-Blind Treatment Period lasting up to 8 weeks, followed by a Single Arm Treatment Period lasting up to 8 weeks, and a 24-Week Safety Follow-Up Period ending with the End of Study Visit at Week 40.

Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis

A Phase 2 Randomized, Double-blind, Placebo-Controlled Study of the Analgesic Efficacy and Safety of the Subcutaneous Administration of the Anti-NGF Antibody Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis

Change in worst pain level during past week from baseline to week 8 measured by NRS-11

Frequency of AEs related to treatment with Tanezumab

Incidence of orthostatic hypotension using postural changes in blood pressure in addition to mean changes in postural blood pressure

Pfizer

Massachusetts General Hospital

Professor of Neurology

Participants will receive an 8-week behavioral intervention which teaches stress management and psychological resiliency-enhancing skills.

Participants will receive and 8-week general stress and health education program, with none of the active relaxation and resiliency-based components being tested in the experimental condition.

8-week group intervention, delivered via Skype, teaching relaxation and psychological resiliency enhancing skills. Topics include the relaxation response, meditation, and yoga.

The Relaxation Response Resiliency Program (3RP) via Skype

Ana-Maria Vranceanu, PhD

This study tests the efficacy of an 8-week, Skype-based, group resiliency training intervention (The Relaxation Response Resiliency Program) for improving psychological stress in patients with Neurofibromatosis. A control group will receive a general health education curriculum. The investigators hypothesize that patients will improve on measures of psychological stress as a result of the resiliency program.

A substudy (Unique Protocol ID: 2013P002605b) has been approved to test this study on a sub-population: patients with NF2 who are hard of hearing.

Resiliency Training for Patients With Neurofibromatosis Via Videoconferencing With Skype

The Satisfaction with Life (SWL) scale is a reliable and valid 5-item self-report measure of global life satisfaction. Responses are made on a 7-point scale with higher scores reflecting higher life satisfaction.

The WHOQOL-BREF comprises of 26 items which measure the following broad domains: physical health, psychological health, social relationships, and environment. The WHOQOL-BREF is a shorter version of the original instrument that may be more convenient for use in large research studies or clinical trials.

The PSS is a widely used psychological instrument for the measurement of the perception of stress. This 10-itam scale is designed to measure the degree to which situations in one's life are appraised, or considered stressful. The scores range from 0-40, with a higher score indicating higher perceived stress. Items were designed to detect how unpredictable, uncontrollable and overloaded respondents find their lives.

The Pain Catastrophizing Scale (PCS) is widely used to assess cognitive and affective responses to pain and to evaluate pain management program outcomes.

The Pain NRS is a scale for patient self-reporting measurements of pain. The measure was depicted by REINS as a standard measure to use in Neurofibromatosis clinical trials.

The PHQ measures symptoms of depression and functional impairment.

The Brief Pain Inventory (BPI) allows patients to rate the severity of their pain (BPI-S) and the degree to which their pain interferes with common dimensions of feeling and function (BPI-I).

The CAMS measures the degree to which individuals experience their thoughts and feelings.

The PGI is an instrument for assessing positive outcomes reported by persons who have experienced traumatic events.

The IRI assesses the cognitive and affective dimensions of empathy.

The Distress Analogue Scales measure participants' levels of stress, coping, distress, and discomfort.

The Epworth Sleepiness Scale (ESS) has been widely used to assess a person's average level of daytime sleepiness in daily life.

The MOCS-A is a 13-item measure assessing participants' current self-perceived status on several skills such as: the ability to relax at will, recognize stress-inducing situations, restructure maladaptive thoughts, be assertive about needs, and choose appropriate coping responses as needed. Responses are made on a 7-point scale with higher scores reflecting higher life satisfaction.

The LOT Optimism Scale measures individual differences in generalized optimism versus pessimism.

The GQ-6 revised is a 6-item measure that assesses individual differences in the proneness to experience gratitude in daily life. Scores range from 6-42, with a higher score indicating a greater sense of gratitude.

The FACIT-Fatigue measures participants' tiredness, weakness, and difficulty conducting usual activities due to fatigue.

The FACIT-Sp measures participants' spiritual well-being (sense of meaning in life and the sense of strength in one's faith) over the past 7 days.

The MOS Social Support Survey measures various dimensions of social support.

The RS-14 measures stress coping ability in the face of adversity.

The Stress and Symptom Management Program 1 (SMP1) introduces and reinforces stress and symptom management skills. The program consists of 8 weekly sessions (90 minutes each), delivered through live videoconferencing.

The Stress and Symptom Management Program 2 (SMP2) introduces and reinforces stress and symptom management skills. The program consists of 8 weekly sessions (90 minutes each), delivered through live videoconferencing.

Stress and Symptom Management Program 1

Stress and Symptom Management Program 2

Christopher J Funes, MS

The aims of this study are to compare the effect and durability of two stress and symptom management programs tailored for patients with neurofibromatosis on quality of life and psychosocial functioning.

The aims of this study are to compare the effect of two stress and symptom management programs tailored for patients with neurofibromatosis on quality of life and psychosocial functioning. We will also examine the degree to which treatment-dependent improvements in quality of life are mediated by improvements in depression, anxiety, distress, mindfulness, gratitude, social support, empathy, optimism, coping, pain intensity and pain interference.

Resiliency Training for Adults With Neurofibromatosis Via Live Videoconferencing

World Health Organization Quality of Life Brief (WHOQOL-BREF); 4-20; higher score indicates higher QoL

Patient Health Questionnaire 9-Item (PHQ-9); 0-27; higher score indicates more symptoms of depression

Generalized Anxiety Disorder 7-Item (GAD-7); 0-21; higher score indicates more symptoms of anxiety

Medical Outcome Study Social Support Survey (MOS); 18-90; higher scores indicate greater perceived social support

Gratitude Questionnaire 6-Item (GQ-6); 6-42; higher scores indicate greater gratitude

Life Orientation Test-Revised (LOT-R); 0-40; higher scores indicate greater optimism

Measure of Current Status Part A (MOCS-A); 0-52; higher scores indicate greater perceived ability to cope

Cognitive and Affective Mindfulness Scale (CAMS); 10-40; higher scores indicate greater mindfulness

Interpersonal Reactivity Index (IRI) Empathy Subscale; 7-Items; 0-28; higher scores indicate greater empathy

Graded Chronic Pain Scale (GCPS); 0-100; higher scores indicate greater pain intensity

PROMIS Pain Interference; 8-40; higher scores indicate more pain interference

Perceived Stress Scale 10-Item (PSS-10); 0-21; higher scores indicate greater levels of perceived stress

Clinical Psychologist

Chronic Pain

Neurologic Manifestations

Chronic Graft Versus Host Disease

Antineoplastic Agents

Bone Density Conservation Agents

Vasodilator Agents

Antibodies, Monoclonal

Erenumab

Immunoglobulin G

Immunoglobulins, Intravenous

Siltuximab

Calcitonin

Salmon calcitonin

Calcitonin Gene-Related Peptide

Katacalcin

Immunologic Factors

The treatment period includes a double-blind treatment period (days 1-84) and an open-label treatment period (days 85-168).

All participants will receive siltuximab during this drug sub-study. Twenty (20) participants will be randomized to receive either Siltuximab or matching placebo during the double-blind treatment period. All participants will receive siltuximab during the open-label treatment period. Participants will complete study procedures as outlined:

* Double-Blind Treatment period: Administration of Siltuximab versus matching placebo in pre-determined dose once every 21 days (for 4 cycles).
* Open-Label Treatment period: Administration of Siltuximab in pre-determined dose once every 21 days (for 4 cycles).

The treatment period includes a single-blind treatment period (days 1-84) and an open-label treatment period (days 85-168).

All participants will receive erenumab-aooe during this drug sub-study. Twenty (20) participants will receive a randomization assignment to receive either Erenumab-Aooe or matching placebo during the single-blind treatment period. All participants will receive erenumab-aooe during the open-label treatment period. Participants will complete study procedures as outlined:

* Single-Blind treatment period (days 1 - 84): Administration of Erenumab-Aooe versus matching placebo in pre-determined dose once every 28 days (for 3 cycles).
* Open-Label Treatment period (days 85-168): Administration of Erenumab-Aooe in pre-determined dose once every 28 days (for 3 cycles).

A chimeric immunoglobulin G mAb, via intravenous infusion.

Human monoclonal antibody, single-dose prefilled SureClick® autoinjector, via subcutaneous injection.

Erenumab-Aooe

Dextrose 5% in water, via intravenous infusion.

Siltuximab Matching Placebo

0.9% saline, 1 mL single-dose prefilled syringe, via subcutaneous injection.

Erenumab-Aooe Matching Placebo

Scott Plotkin, MD, PhD

Lei Xu, PhD

Lauren Hibyan, RN

Marie Aste, RN

Scott Plotkin, MD

This is a placebo-controlled, multi-arm phase II platform screening trial designed to test the safety, pain responses, and pharmacodynamic activity of multiple experimental therapies simultaneously in participants with moderate-to-severe pain due to schwannomatosis (SWN).

This Master Study is being conducted as a platform that may allow participants with pain associated with schwannomatosis to receive a novel intervention throughout this study. Embedded within the Master Study are individual drug sub-studies:

* Investigational Drug Sub-Study A: Siltuximab
* Investigation Drug Sub-Study B: Erenumab-Aooe

This is a placebo-controlled, multi-arm phase II platform screening trial designed to test the safety, pain responses, and pharmacodynamic activity of multiple experimental therapies simultaneously in participants with moderate-to-severe pain due to schwannomatosis (SWN).

The MASTER STUDY has no study drug or intervention. It is intended to enroll participants who will be placed into different treatment arms (SUB-STUDIES), which will each have an additional consent and enrollment process.

MASTER STUDY

* The research study procedures include screening for eligibility, randomization to an experimental treatment sub-study, if qualified, and observation for up to 10 years.

  * Subjects who complete treatment on one experimental arm will be permitted to enroll in a different experimental treatment arm if they meet eligibility criteria.
  * Participants who are not eligible for enrollment in a different treatment sub-study will be permitted to remain under observation on this Master Study to understand the natural history of schwannomatosis-related pain and tumor growth pattern.
  * Participants will be eligible to remain on this Master Study for up to 10 years.
  * It is expected that about 40 people will take part in the Master Study.
  * The study will randomize a maximum of 20 participants to each of the experimental arms. The overall size of the trial is not fixed by design because it includes arm-dropping rules for futility and allow for the possibility of arm addition by amendment.
* Upon meeting Master Study qualifications, participant will be randomly assigned to a treatment sub-study.

SUB-STUDY A - SILTUXIMAB

* The purpose of this study is to find out what effects, good and/or bad, siltuximab has on schwannomatosis-associated pain.
* The U.S. Food and Drug Administration (FDA) has not approved Siltuximab for schwannomatosis but it has been approved for the treatment of people with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.
* Siltuximab was identified as a potential treatment for schwannomatosis tumors in a screen of compounds in a laboratory. Siltuximab is believed to work by blocking the growth signals and inflammation in tumor cells.
* Upon meeting sub-study qualifications, participant will be randomly assigned to either the early-start group or the delayed-start group.
* Twenty (20) people will take part in the siltuximab Sub-study.
* Participants in the early-start group will receive siltuximab every 3 weeks over 168 days. Participants in the delayed-start group will receive placebo every 3 weeks for the first 84 days followed by siltuximab every 3 weeks over the subsequent 84 days (for a total of 168 days).

SUB-STUDY B - ERENUMAB-AOOE

* The purpose of this study is to find out what effects, good and/or bad, erenumabaooe has on schwannomatosis-associated pain.
* The U.S. Food and Drug Administration (FDA) has not approved Erenumab-Aooe for schwannomatosis but has approved it for treatment of migraines headaches in adults.
* Erenumab-Aooe was identified as a potential treatment for schwannomatosis pain. Erenumab-aooe acts by blocking pain signals in the body. By blocking pain signals, erenumabaooe may reduce pain associated with schwannomatosis.
* Upon meeting sub-study qualifications, participant will be randomly assigned to either the early-start group or the delayed-start group.
* Twenty (20) people will take part in the ERENUMAB-AOOE Sub-study.
* Participants in the early-start group will receive erenumab-aooe every 4 weeks over 168 days. Participants in the delayed-start group will receive placebo every 4 weeks for the first 84 days followed by erenumab-aooe every 4 weeks over the subsequent 84 days (for a total of 168 days).

(1) Double-Blind period for Siltuximab or Placebo Arm; and (2) Single-Blind period for Erenumab-Aooe or Placebo Arm

Screening Trial for Pain Relief in Schwannomatosis (STARFISH)

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: \[contact information for Sponsor Investigator or designee\]. 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 change in the worst pain intensity between baseline and day 85. Worst pain is measured using the 11-point Pain Intensity Numerical Rating Scale (NRS), where scores range from 0 (no pain) to 10 (worst pain ever) of the maximum SWN-related pain experienced over the past week

Graded according to NCI CTCAE v5.0. All participants will be evaluable for toxicity from the time of first treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neurofibromatosis (NF) Registry Portal	NCT01885767	Neurofibromatos... Neurofibromatos... Schwannomatosis		-	The Children's Tumor Foundation
Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis	NCT04163419	Schwannomatosis Pain	Tanezumab Placebo	18 Years -	Massachusetts General Hospital
Resiliency Training for Patients With Neurofibromatosis Via Videoconferencing With Skype	NCT02298270	Neurofibromatos... Neurofibromatos... Neurofibromatos... Schwannomatosis	The Relaxation ...	18 Years -	Massachusetts General Hospital
Resiliency Training for Adults With Neurofibromatosis Via Live Videoconferencing	NCT03406208	Neurofibromatos... Neurofibromatos... Neurofibromatos... Schwannomatosis	Stress and Symp... Stress and Symp...	18 Years -	Massachusetts General Hospital
Screening Trial for Pain Relief in Schwannomatosis (STARFISH)	NCT05684692	Schwannomatosis Schwannomas Pain, Chronic	Siltuximab Erenumab-Aooe Siltuximab Matc... Erenumab-Aooe M...	18 Years -	Massachusetts General Hospital
Resiliency Training for Patients With Neurofibromatosis Via Videoconferencing With Skype	NCT02298270	Neurofibromatos... Neurofibromatos... Neurofibromatos... Schwannomatosis	The Relaxation ...	18 Years -	Massachusetts General Hospital
Resiliency Training for Patients With Neurofibromatosis Via Videoconferencing With Skype	NCT02298270	Neurofibromatos... Neurofibromatos... Neurofibromatos... Schwannomatosis	The Relaxation ...	18 Years -	Massachusetts General Hospital
Resiliency Training for Adults With Neurofibromatosis Via Live Videoconferencing	NCT03406208	Neurofibromatos... Neurofibromatos... Neurofibromatos... Schwannomatosis	Stress and Symp... Stress and Symp...	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for schwannomatosis