Screening Trial for Pain Relief in Schwannomatosis (STARFISH)
Abstract
Patients with schwannomatosis (SWN) are at increased risk for multiple types of benign nervous system tumors, including schwannomas and meningiomas. Chronic pain is common in SWN patients, affecting 83% of patients enrolled in a study involving the International Schwannomatosis Registry. Seventy-six percent of these individuals reported use of pain medications but 61% still rated their pain as moderate to severe in intensity (as estimated by the Numeric Rating Scale-11, a self-reported questionnaire that asks patients to rank pain from no pain 0 to worst pain imaginable 10). Chronic pain usually persists, despite aggressive surgical and medical management, and identifying effective treatments remains an important unmet medical need for SWN patients. Currently, the development of novel treatments for SWN-related pain is extremely slow and inefficient. Preclinical models of SWN-related pain are limited, since non-cancerous schwannomas do not grow well in laboratory animals. In addition, clinical trials are challenging to execute since SWN is a rare disorder. Thus, virtually no drugs successfully pass through the development pathway to enter clinical trials. Recognizing that one of the biggest challenges in basic and translational SWN research is the lack of clinically relevant models, we successfully established patient-derived SWN cell lines and orthotopic patient-derived xenograft (PDX) tumor mouse model. Our preclinical laboratory evidence suggests that inflammation in schwannomas – manifested as an increase in calcitonin-related gene peptide (CGRP) – plays a key role in the generation of SWN-related pain. We have established the Screening Trial for Pain Relief in Schwannomatosis (STARFISH) trial, which enrolls SWN participants with moderate to severe pain and assigns them to different medical treatment arms. The goal of this platform trial is to rapidly and efficiently screen therapies for SWN-associated pain. We hypothesize that erenumab-aooe, a Food and Drug Administration (FDA)-approved antibody that neutralizes CGRP, will be effective in treating moderate-to-severe pain in patients with SWN. In this novel phase II trial, 20 participants will be treated with erenumab-aooe on this sub-study. Because the use of a placebo control is the gold-standard for assessing effectiveness in short-term pain studies, the trial will begin with half of participants receiving the study drug and half receiving a placebo; halfway through the trial, all participants will receive the study drug to ensure that no participants are treated with a placebo only. Clinical benefit will be measured by self-report of pain intensity using the NRS-11 pain intensity scale; multiple aspects of quality of life will be measured using validated surveys. Side effects will be monitored throughout the trial. Erenumab-aooe is approved by the FDA for treatment of migraine headaches. The drug will be purchased for the study. Erenumab-aooe will be administered at home beneath the skin (subcutaneously) every 4 weeks for up to 6 months. Reported side effects of erenumab-aooe have been mild and include injection site reaction (6%), constipation (3%), and cramps (2%). Participants who complete treatment on erenumab-aooe will be permitted to enroll in a different treatment arm of the STARFISH trial as they become available on the study, provided they meet the eligibility criteria. The STARFISH trial is the first platform trial for SWN patients with moderate to severe pain. This novel trial design will help overcome key barriers to clinical trials for SWN such as the rarity of SWN, the difficulty in recruiting participants, and the cost of running clinical trials. This drug study will evaluate erenumab-aooe, a widely available and safe drug, for pain relief in SWN. If erenumab-aooe appears to be effective in this trial, a larger study to confirm clinical benefit would be indicated and, if successful, would lead to the first medical tre
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210439
Entities
People
- Scott R. Plotkin
Organizations
- Massachusetts General Hospital
- United States Army