A Phase I/II study of Brigatinib in pediatric and young adult patients with ALK+ Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors or other solid tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 54
- 试验地点
- 28
- 主要终点
- Phase 1: dose-limiting toxicities (DLTs) during the first course of therapy.
研究概览
简要总结
To determine the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors, including ALK+ IMT. To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors, including ALK+ IMT. To establish the anti-tumor activity of single agent brigatinib when administered to children with ALK+ IMT. To establish the efficacy of single agent brigatinib when administered to children with ALK+ ALCL for a duration of 2 years, without planned HSCT in consolidation.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 0 years 至 64 years（0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Patients must be ≥ 1 and < 26 years of age at the time of enrollment, and able to swallow brigatinib tablets at the time of enrollment, with a minimum weight of 10 kg.
- •Patients must have a histologically confirmed diagnosis of cancer at baseline. In patients where a repeat biopsy at relapse (or moment of refractory disease) is considered not feasible by the treating physician, archived material from diagnosis needs to be available for central review.
- •Patients are required to provide prior results showing an activating ALK aberration in the tumor per local laboratory results, and material needs to be available for central laboratory confirmation of ALK status. For ALK+ ALCL, detection of ALK with immunohistochemistry (IHC) is sufficient for inclusion, all others require molecular evidence of a ALK fusion gene or mutation by FISH, PCR or NGS. ALK detection will be confirmed centrally with FISH.
- •Phase 1: • Patients with ALCL must be relapsed/refractory or intolerant to standard therapies. Refractory disease for ALCL is defined as: o no response to at least one course of ALCL99/other standard of care chemotherapy (SD or PD of measurable lesions), and/or o MRD-positivity by qualitative PCR for NPM-ALK after at least one course of ALCL99/other standard of care chemotherapy (before the second course of chemotherapy). • Patients with relapsed/refractory (R/R) IMT must not be suitable for curative surgical resection without causing mutilation. Newly diagnosed patients with locally advanced IMT, for whom surgery may not be feasible for close proximity to vital structures, without prior tumor-shrinkage, may also be included, as well as metastatic disease. • Patients with other solid tumors (excluding IMT) must have relapsed or refractory disease.
- •Phase 2: • Patients with ALCL must be relapsed/refractory. Refractory disease for ALCL is defined as: o no response to at least one course of ALCL99/other standard of care chemotherapy (SD or PD of measurable lesions), and/or o MRD-positivity by qualitative PCR for NPM-ALK after at least one course of ALCL99/other standard of care chemotherapy (before the second course of chemotherapy). • Patients with R/R IMT Relapsed/refractory IMT, or newly diagnosed, including locally advanced and metastatic IMT which cannot be surgically resected without causing mutilation.
- •Performance Status: • Karnofsky performance status ≥40% for patients >16 years of age or Lansky Play Scale ≥40% for patients ≤16 years of age for ALCL patients in phase
- •Karnofsky performance status ≥50% for patients >16 years of age or Lansky Play Scale ≥50% for patients ≤16 years of age, for IMT and other solid tumors and for ALCL patients in phase
- •Patients must not be receiving other investigational medications (defined as medicinal products not yet approved for any indications, including alternative/herbal therapies) within 30 days of first dose of study drug or while on study.
排除标准
- •Patients receiving systemic treatment with strong or moderate CYP3A inhibitors or inducers within 14 days or five half-lives, whichever the less, prior to the first dose of study drug (refer to Section 5.2 for a list of example medications).
- •Diagnosis of another concurrent primary malignancy.
结局指标
主要结局
Phase 1: dose-limiting toxicities (DLTs) during the first course of therapy.
Phase 1: dose-limiting toxicities (DLTs) during the first course of therapy.
Phase 1: Brigatinib plasma PK parameters to be determined: o maximum observed concentration (Cmax), o time of first occurrence of maximum observed concentration (Tmax), o area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast).
Phase 1: Brigatinib plasma PK parameters to be determined: o maximum observed concentration (Cmax), o time of first occurrence of maximum observed concentration (Tmax), o area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast).
Phase 1: The RP2D will be selected by the DSMB and will be based on the dose that results in equivalent (approximately ±20% of the adult values) PK exposure to the adult comparator and with <2 out of 6 patients at this dose level present with a DLT and taking into account responses observed in phase 1.
Phase 1: The RP2D will be selected by the DSMB and will be based on the dose that results in equivalent (approximately ±20% of the adult values) PK exposure to the adult comparator and with <2 out of 6 patients at this dose level present with a DLT and taking into account responses observed in phase 1.
Cohort B1: Overall response rate (ORR), defined as the percentage of patients with CR or PR according to RECIST 1.1 after 1 course and best ORR during brigatinib treatment.
Cohort B1: Overall response rate (ORR), defined as the percentage of patients with CR or PR according to RECIST 1.1 after 1 course and best ORR during brigatinib treatment.
Cohort B2: EFS (using the IPNHL response criteria), defined as the time between start of study treatment and first event being progressive disease, relapse, death of any cause and second malignancies, whatever happens first. Patients consolidated with HSCT will be censored.
Cohort B2: EFS (using the IPNHL response criteria), defined as the time between start of study treatment and first event being progressive disease, relapse, death of any cause and second malignancies, whatever happens first. Patients consolidated with HSCT will be censored.
次要结局
未报告次要终点
研究者
Michel Zwaan
Scientific
Prinses Maxima Centrum voor Kinderoncologie B.V.