Screening Trial for Pain Relief in Schwannomatosis (STARFISH)

NCT05684692 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-512
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Schwannomatosis; Schwannomas; Pain, Chronic

Keywords

Schwannomatosis; Schwannomas; Pain; chronic Pain; Severe Pain

Outcome Measures

Primary Outcomes (1)

• Change in worst pain intensity for each drug sub-study

  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

  Baseline to week 12

Secondary Outcomes (1)

• Number of Participants with Adverse Events in each drug sub-study

  Randomization/1st treatment to 4 weeks post final treatment

Study Arms (2)

Sub-study A: Siltuximab

EXPERIMENTAL

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).

Drug: Siltuximab; Drug: Siltuximab Matching Placebo

Sub-study B: Erenumab-Aooe

EXPERIMENTAL

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).

Drug: Erenumab-Aooe; Drug: Erenumab-Aooe Matching Placebo

Interventions

Siltuximab DRUG

A chimeric immunoglobulin G mAb, via intravenous infusion.

Also known as: Sylvant

Sub-study A: Siltuximab

Erenumab-Aooe DRUG

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

Also known as: Aimovig

Sub-study B: Erenumab-Aooe

Siltuximab Matching Placebo DRUG

Dextrose 5% in water, via intravenous infusion.

Also known as: Normal Saline

Sub-study A: Siltuximab

Erenumab-Aooe Matching Placebo DRUG

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

Also known as: Normal Saline

Sub-study B: Erenumab-Aooe

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a confirmed diagnosis schwannomatosis by fulfilling either clinical or molecular diagnosis.
• Clinical diagnosis: A clinical diagnosis of schwannomatosis is confirmed by either of the two following criteria:

You may not qualify if:

• one pathologically confirmed schwannoma or intracranial meningioma and
• An affected first-degree relative. Molecular diagnosis
• A molecular diagnosis of schwannomatosis is confirmed by either (1) two or more pathologically proven schwannomas or meningiomas AND genetic studies of at least two tumors with loss of heterozygosity (LOH) for chromosome 22 and two different NF2 mutations; or (2) one pathologically proven schwannoma or meningioma and a germline SMARCB1 or LZTR1 pathogenic mutation.
• Participant must be ≥ 18 years of age on Day 1 of treatment.
• Karnofsky performance status ≥ 70 or ECOG PS 0 or 1 (see Appendix A).
• Subject must have moderate-to-severe pain secondary to SWN, defined as Score ≥5 on the Numeric Rating Scale-11 (NRS-11) as the maximum pain intensity in the previous 7 days.
• Ability to understand and the willingness to sign written informed consent and assent documents.
• Must have established relationship with primary care physician and provide contact information.
• Participants must be willing and able to provide written informed consent/assent for the siltuximab arm of the STARFISH trial.
• Subject must have moderate to severe pain secondary to schwannomatosis, defined as having a median Numeric Rating Scale-11 (NRS-11) score ≥5 during screening.
• Subject must have insufficient response to, intolerance of, be unwilling to try, or contraindication to medical therapies for SWN-related pain, such as NSAID therapy, opioid treatment, or neuropathic pain medications.
• Clinical laboratory values as specified below within 28 days before the first dose of study drug:
• ALT/aspartate aminotransferase (AST) ≤ 2.5 × institutional upper limit of normal (ULN);
• Total serum bilirubin ≤ 1.5 × institutional ULN (\<3.0 × institutional ULN for patients with Gilbert syndrome)
• Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, using the modification of diet in renal disease (MDRD) equation

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• United States Department of Defense: collaborator
• RECORDATI GROUP: collaborator

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02215, United States

RECRUITING

Related Publications (1)

• Yin Z, Wu L, Zhang Y, Sun Y, Chen JW, Subudhi S, Ho W, Lee GY, Wang A, Gao X, Ren J, Zhu C, Zhang N, Ferraro GB, Muzikansky A, Zhang L, Stemmer-Rachamimov A, Mao J, Plotkin SR, Xu L. Co-Targeting IL-6 and EGFR signaling for the treatment of schwannomatosis and associated pain. bioRxiv [Preprint]. 2023 Feb 6:2023.02.06.527377. doi: 10.1101/2023.02.06.527377.

  PMID: 36798353 DERIVED

MeSH Terms

Conditions

Schwannomatosis; Neurilemmoma; Chronic Pain; Pain

Interventions

siltuximab; erenumab; Saline Solution

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Scott Plotkin, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Scott Plotkin, MD, PhD

CONTACT

617-643-8992; lmhibyan@partners.org

Lei Xu, PhD

CONTACT

617-726-8051; lei@steele.mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: (1) Double-Blind period for Siltuximab or Placebo Arm; and (2) Single-Blind period for Erenumab-Aooe or Placebo Arm
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 5, 2023
• First Posted: January 13, 2023
• Study Start: August 31, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)