Screening Trial for Pain Relief in Schwannomatosis (STARFISH)

Inclusion Criteria for Master Study: * 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: * Two or more non-intradermal schwannomas, one with pathological confirmation, without evidence of bilateral vestibular schwannoma (see exclusion criteria 3.2.3) OR * 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. Inclusion Criteria for Sub-study A - Siltuximab or Placebo Arm: * 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 * Serum lipase ≤1.5 × institutional ULN * Absolute neutrophil count ≥1.5 × 109/L * Platelet count ≥75 × 109/L * Hemoglobin ≥9 g/dL and \<17 g/dL * Female subjects of childbearing potential and at risk for pregnancy (e.g., not abstinent) must agree to use 2 highly effective methods of contraception throughout the study and for 100 days (15 weeks) after the last dose of assigned study medication. * Female subjects of non-childbearing potential must meet at least 1 of the following criteria: * Have undergone documented total hysterectomy or bilateral oophorectomy * Have medically confirmed ovarian failure * Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; \[status may be confirmed with/and have\] a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state; In the event of indeterminate or anomalous results on pregnancy/FSH testing or issues surrounding contraceptive requirements, the study clinician should be contacted and will make the final decision as to the adequacy/need for contraception. Inclusion Criteria for Sub-study B - Erenumab-Aooe or Placebo Arm: * Participants must be willing and able to provide written informed consent/assent for the erenumab-aooe arm of the STARFISH trial. * Subject must have moderate to severe pain secondary to schwannomatosis, defined as a median NRS-11 Score ≥5 during Screening. * Subject must have insufficient response to, unwillingness to take, intolerance of, or contraindication to at least one 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 * Serum lipase ≤1.5 × institutional ULN * Absolute neutrophil count ≥1.5 × 109/L * Platelet count ≥75 × 109/L * Hemoglobin ≥9 g/dL * Female subjects of childbearing potential and at risk for pregnancy (e.g., not abstinent) must agree to use 2 highly effective methods of contraception throughout the study and for 60 days after the last dose of assigned study medication. * Female subjects of non-childbearing potential must meet at least 1 of the following criteria: * Have undergone documented total hysterectomy or bilateral oophorectomy * Have medically confirmed ovarian failure * Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; \[status may be confirmed with/and have\] a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state; In the event of indeterminate or anomalous results on pregnancy/FSH testing or issues surrounding contraceptive requirements, the study clinician should be contacted and will make the final decision as to the adequacy/need for contraception. Exclusion Criteria for Master Study: * Participants who have had chemotherapy within a minimum of 4 weeks prior to Master Study registration (or a minimum of 5 half-lives and resolution to baseline of toxicities unless there are