NCT06540963招募中2 期
Phase II Trial of Tipifarnib and Naxitamab for Relapsed/Refractory Neuroblastoma
Giselle Sholler12 个研究点 分布在 1 个国家目标入组 98 人开始时间: 2024年12月6日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 98
- 试验地点
- 12
- 主要终点
- Determine the Overall Response Rate (ORR) of Participants using INSS Response
研究概览
简要总结
The purpose of this study is to evaluate the investigational drug, tipifarnib (a pill taken by mouth), in combination with the Food and Drug Administration (FDA) approved drug, naxitimab, administered intravenously (IV; a liquid that continuously goes into your body through a tube that has been placed during a surgery into one of your veins). Naxitamab is FDA approved for pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy, it may not be approved in the type of disease used in this study.
The goals of this part of the study are:
- Test the safety and tolerability of tipifarnib in combination with naxitimab in participants with cancer
- To determine the activity of study treatments chosen based on:
- How each participant responds to the study treatment
- How long a participant lives without their disease returning/progressing
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be age ≤ 21 years at initial diagnosis. Participants must be >12 months of age at enrollment. Safety Run-In (first 6 participants) must be age 6 years or older. As of 09Jun2026 the safety run-in is complete.
- •Pathology: All participants must have a pathologically confirmed diagnosis of neuroblastoma at any point in their treatment.
- •Tumor assessment: Disease staging must be performed. This disease assessment is required for eligibility and must be done within a maximum of 4 weeks before first dose of study drug.
- •Disease Status: Relapsed/Refractory Neuroblastoma Relapsed disease defined as neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol) and has now relapsed and is in any number of relapses.
- •Refractory disease defined as High-risk neuroblastoma as defined by the International Neuroblastoma Risk Group Staging System (INRG) that failed to achieve complete response (CR) after at least 4 cycles of aggressive multi-drug induction chemotherapy, progression during upfront therapy, or with disease remaining after standard immunotherapy.
- •INRG High Risk NB defined as one of the following:
- •Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M with MYCN amplification
- •Age ≥ 547 days and INRG Stage M regardless of biologic features
- •Any age initially diagnosed with INRG Stage L1 MYCN amplified neuroblastoma (NBL) who have progressed to Stage M without systemic chemotherapy
- •Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to Stage M without systemic chemotherapy
- •Measurable Disease: Participants must be relapsed or refractory with active disease. Participants must have measurable or evaluable disease, including at least one of the following: Measurable tumor >10mm by computed tomography scan (CT) or magnetic resonance imaging (MRI); a positive metaiodobenzylguanidine (MIBG) scan or positron emission tomography (PET) scan or Positive bone marrow biopsy/aspirate.
- •Cohort 1- High-risk neuroblastoma patients with disease limited to bone and/or bone marrow at enrollment. Participant must have stable disease, minor response, or partial response to their most recent therapy.
- •Cohort 2- All other high-risk relapsed or refractory neuroblastoma patients not eligible for Cohort 1, including participants with soft tissue disease.
- •Participants with central nervous system (CNS) disease currently taking steroids must have been on a stable dose of steroids for at least one week prior to their biopsy and must not have progressive hydrocephalus at enrollment.
- •Timing from prior therapy:
- •Participants must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:
- •Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
- •Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
- •Small Molecule Inhibitors (anti-neoplastic agent): At least 7 days since the completion of therapy with a small molecule inhibitor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.
- •Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells, anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.).
- •XRT (Radiotherapy): At least 30 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
- •Stem Cell Transplant:
- •Allogeneic: No evidence of active graft vs. host disease
- •Allo/Auto: ≥ 2 months must have elapsed since transplant.
- •MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.
- •Participants must have a Lansky or Karnofsky Performance Scale score of ≥ 50
- •Participants must have adequate organ function at the time of enrollment:
- •Hematological: Hematological recovery as defined by absolute neutrophil count (ANC) ≥750/μL, platelets ≥30/μL (may be transfused).
- •Liver: Normal liver function as defined by Aspartate transferase (AST), Alanine transaminase (ALT), and total bilirubin (TBL) all within upper limit of normal
- •For participants < 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m
- •The Bedside Schwartz equation is: [(0.413) X (Height in cm)] / SCr
- •For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m
- •The Cockcroft and Gault formula is: [(140-age) x (Wt in kg) x (0.85 if female)] / (72 x SCr)
- •Cardiac: Participants must have a QTcF ≤ 470 msc.
- •Participants of childbearing potential must have a negative pregnancy test. Participants of childbearing potential must agree to use an effective birth control method.
- •Participants who are lactating must agree to stop breast-feeding. (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
- •Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).
排除标准
- •Participants who are less than 1 year of age
- •BSA of <0.25 m2
- •Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.
- •Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.
- •Infection: Participants who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
- •Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
- •Previous Gr.4 allergic or anaphylactic reaction to naxitamab, leading to the discontinuation of naxitamab during prior therapy.
研究组 & 干预措施
HRNB Bone/Bone Marrow
Experimental
Cycles 1-6: Tipifarnib and Naxitamab Tipifarnib: on days 1-7 and 15-21 of each 28-day cycle. Naxitamab IV on Days 1, 3, and 5 of each cycle.
干预措施: Tipifarnib (Drug)
HRNB Bone/Bone Marrow
Experimental
Cycles 1-6: Tipifarnib and Naxitamab Tipifarnib: on days 1-7 and 15-21 of each 28-day cycle. Naxitamab IV on Days 1, 3, and 5 of each cycle.
干预措施: Naxitamab (Drug)
HRNB All others
Experimental
Cycles 1-6: Tipifarnib and Naxitamab Tipifarnib: on days 1-7 and 15-21 of each 28-day cycle. Naxitamab IV on Days 1, 3, and 5 of each cycle.
干预措施: Tipifarnib (Drug)
HRNB All others
Experimental
Cycles 1-6: Tipifarnib and Naxitamab Tipifarnib: on days 1-7 and 15-21 of each 28-day cycle. Naxitamab IV on Days 1, 3, and 5 of each cycle.
干预措施: Naxitamab (Drug)
结局指标
主要结局
Determine the Overall Response Rate (ORR) of Participants using INSS Response
时间窗: 6 months
To evaluate the activity of Tipifarnib in combination with Naxitamab based on Overall response rate (ORR)
次要结局
- Length of time that participants experience Overall Survival (OS)(6 months plus 5 years follow up)
- Number of participants with progression free survival (PFS) during study(6 months plus 5 years follow up)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(6 months plus 30 days)
研究者
Giselle Sholler
Beat Childhood Cancer Chair
Milton S. Hershey Medical Center
研究点 (12)
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