Screening Trial for Pain Relief in Schwannomatosis (STARFISH)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Change in worst pain intensity for each drug sub-study
研究概览
简要总结
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
详细描述
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
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The research study procedures include screening for eligibility, randomization to an experimental treatment sub-study, if qualified, and observation for up to 10 years.
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Subjects who complete treatment on one experimental arm will be permitted to enroll in a different experimental treatment arm if they meet eligibility criteria.
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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.
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Participants will be eligible to remain on this Master Study for up to 10 years.
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It is expected that about 40 people will take part in the Master Study.
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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.
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Upon meeting Master Study qualifications, participant will be randomly assigned to a treatment sub-study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
(1) Double-Blind period for Siltuximab or Placebo Arm; and (2) Single-Blind period for Erenumab-Aooe or Placebo Arm
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 irreversible toxicities from prior drug that do not influence risk of next drug).
- •Participants who are receiving any other investigational agents.
- •Participants with nervous system tumors that, in the opinion of the treating investigator, are likely to require active treatment (including surgery) within 6 months of registration to the Master Study.
- •History of a malignancy in the last 3 years, unless (a) have been disease-free for at least 2 years or (b) are deemed by the treating investigator to be at low risk for progression or recurrence of that malignancy (e.g., carcinoma in situ, basal cell carcinoma, Gleason 6 prostate cancer) in the next 2 years
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Exclusion Criteria for Sub-study A - Siltuximab or Placebo Arm:
- •Subject has a history of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG fusion protein.
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研究组 & 干预措施
Sub-study B: Erenumab-Aooe
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).
干预措施: Erenumab-Aooe Matching Placebo (Drug)
Sub-study A: Siltuximab
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).
干预措施: Siltuximab Matching Placebo (Drug)
Sub-study B: Erenumab-Aooe
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).
干预措施: Erenumab-Aooe (Drug)
Sub-study A: Siltuximab
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).
干预措施: Siltuximab (Drug)
结局指标
主要结局
Change in worst pain intensity for each drug sub-study
时间窗: Baseline to week 12
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
次要结局
- Number of Participants with Adverse Events in each drug sub-study(Randomization/1st treatment to 4 weeks post final treatment)
研究者
Scott R. Plotkin, MD, PhD
Principal Investigator
Massachusetts General Hospital