NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of Erdafitinib in Patients With Tumors Harboring FGFR1/2/3/4 Alterations
概览
- 阶段
- 2 期
- 干预措施
- Biospecimen Collection
- 疾病 / 适应症
- Advanced Malignant Solid Neoplasm
- 发起方
- National Cancer Institute (NCI)
- 入组人数
- 20
- 试验地点
- 231
- 主要终点
- Objective Response Rate
- 状态
- 进行中（未招募）
- 最后更新
- 10天前
概览
简要总结
This phase II Pediatric MATCH trial studies how well erdafitinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with FGFR mutations that have spread to other places in the body and have come back or do not respond to treatment. Erdafitinib may stop the growth of cancer cells with FGFR mutations by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with erdafitinib with advanced solid tumors (including central nervous system \[CNS\] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor genetic alterations in the FGFR1/2/3/4 pathway. SECONDARY OBJECTIVES: I. To estimate the progression free survival in pediatric patients treated with erdafitinib with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor genetic alterations in the FGFR1/2/3/4. II. To obtain information about the tolerability of erdafitinib in children with relapsed or refractory cancer. III. To provide preliminary estimates of the pharmacokinetics of erdafitinib in children 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 erdafitinib orally (PO) once daily (QD) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study. After completion of study treatment, patients are followed up periodically.
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 molecular analysis for therapy choice (MATCH) to APEC1621B based on the presence of an actionable mutation as defined in APEC1621SC
- •Patients must be \>/= 12 months and =/\< 21 years of age at the time of study enrollment
- •Patients must have a body surface area \>/= 0.53 m\^2 at 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 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 cerebrospinal fluid (CSF)
- •Previously radiated lesions that have not demonstrated clear progression post radiation
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 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 an effective contraceptive method, while receiving study treatment and for 3 months after the last dose of erdafitinib; male subjects (with a partner of child-bearing potential) must use a condom with spermicide when sexually active and must not donate sperm from the first dose of study drug until 3 months after the last dose of study drug
- •Concomitant medications
- •Corticosteroids: 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
- •Investigational drugs: patients who are currently receiving another investigational drug are not eligible
- •Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
- •Anti-GVHD agents post-transplant: 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
- •CYP3A4 agents: patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible; Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
- •CYP2C9 agents: patients who are currently receiving drugs that are strong inducers or moderate inhibitors of CYP2C9 are not eligible
- •Patients who have an uncontrolled infection are not eligible
- •Patients who have received a prior solid organ transplantation are not eligible
研究组 & 干预措施
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Biospecimen Collection
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Bone Marrow Aspiration and Biopsy
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Bone Scan
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Computed Tomography
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Erdafitinib
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Magnetic Resonance Imaging
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Pharmacological Study
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Positron Emission Tomography
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Radionuclide Imaging
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: X-Ray Imaging
Treatment (erdafitinib)
Patients receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Laboratory Biomarker Analysis
结局指标
主要结局
Objective Response Rate
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
- Percentage of Patients Experiencing Grade 3 or Higher Adverse Events(Up to 2 years from study entry)
- Progression Free Survival (PFS)(Up to 6 months from study entry)
- Pharmacokinetic (PK) Parameters(Pre-dose Cycle 2 Day 1; 1-hour post-dose Cycle 2 Day 1; 2-hour post dose Cycle 2, Day 1; 4-hour post-dose Cycle 2, Day 1; 6-8-hour post-dose, Cycle 2 Day 1; 24-hour post dose, Cycle 2, Day 2)