NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of LOXO-292 in Patients With Tumors Harboring RET Gene Alterations
概览
- 阶段
- 2 期
- 干预措施
- Selpercatinib
- 疾病 / 适应症
- Hematopoietic and Lymphatic System Neoplasm
- 发起方
- National Cancer Institute (NCI)
- 入组人数
- 1
- 试验地点
- 348
- 主要终点
- Objective Response Rate (Complete Response + Partial Response) in Pediatric Patients Treated With Selpercatinib (LOXO-292)
- 状态
- 进行中（未招募）
- 最后更新
- 8天前
概览
简要总结
This phase II pediatric MATCH treatment trial studies how well selpercatinib works in treating patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), lymphomas, or histiocytic disorders that have activating RET gene alterations. Selpercatinib may block the growth of cancer cells that have specific genetic changes in an important signaling pathway (called the RET pathway) and may reduce tumor size.
详细描述
PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with selpercatinib (LOXO-292) with advanced solid tumors (including central nervous system \[CNS\] tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the RET pathway. SECONDARY OBJECTIVES: I. To estimate the progression free survival in pediatric patients treated with selpercatinib (LOXO-292) with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the RET pathway. II. To obtain information about the tolerability of selpercatinib (LOXO-292) in children and adolescents with relapsed or refractory cancer. EXPLORATORY OBJECTIVE: I. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA). OUTLINE: Patients receive selpercatinib orally (PO) twice daily (BID) on days 1-28 on study. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial. After completion of study treatment, patients are followed for 30 days, then periodically thereafter.
研究者
入排标准
入选标准
- •Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621N based on the presence of an actionable mutation
- •Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
- •Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
- •Note: The following do not qualify as measurable disease:
- •Malignant fluid collections (e.g., ascites, pleural effusions)
- •Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
- •Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma
- •Elevated tumor markers in plasma or cerebral spinal fluid (CSF)
- •Previously radiated lesions that have not demonstrated clear progression post radiation
- •Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
排除标准
- •Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two (2) highly effective contraceptive method for the duration of study treatment and for at least 2 weeks after the last dose of selpercatinib (LOXO-292). Male study participants are to refrain from sperm donation during treatment and for 2 weeks after the last dose of selpercatinib (LOXO-292)
- •Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
- •Patients who are currently receiving another investigational drug are not eligible
- •Patients who are currently receiving other anti-cancer agents are not eligible
- •Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
- •Patients who are currently receiving drugs that are moderate or strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
- •Proton pump inhibitors (PPIs), H2 receptor antagonists and antacids: Concomitant use of PPIs during selpercatinib (LOXO-292) therapy should be avoided if feasible. If co-administration of selpercatinib and PPI is necessary, administer selpercatinib with a meal. If H2 receptor antagonist is necessary, administer selpercatinib 2 hours before or 10 hours after H2 receptor antagonist administration. If antacid use is necessary, administer selpercatinib 2 or more hours before or 2 or more hours after antacid administration
- •Patients who have major surgery within 14 days prior to cycle 1 day 1 (C1D1) are not eligible. (Central line placement or subcutaneous port placement is not considered major surgery)
- •Patients with known clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of selpercatinib (LOXO-292) are excluded
- •Patients with known hypersensitivity to any of the components of the investigational agent, LOXO 292 are excluded
研究组 & 干预措施
Treatment (selpercatinib)
Patients receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Selpercatinib
Treatment (selpercatinib)
Patients receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: X-Ray Imaging
Treatment (selpercatinib)
Patients receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Computed Tomography
Treatment (selpercatinib)
Patients receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Magnetic Resonance Imaging
Treatment (selpercatinib)
Patients receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Positron Emission Tomography
Treatment (selpercatinib)
Patients receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Radionuclide Imaging
结局指标
主要结局
Objective Response Rate (Complete Response + Partial Response) in Pediatric Patients Treated With Selpercatinib (LOXO-292)
时间窗: Up to 2 years from study entry
A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders. The revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to determine response and progression in this study, with specific criteria outlined for the different subtypes of tumors (e.g., 2-dimensional measurements for central nervous system \[CNS\] tumors).
次要结局
- Progression-free Survival (PFS)(Up to 6 months from study entry)
- Percentage of Patients Experiencing Grade 3 or 4 Adverse Events(Up to 2 years from study entry)