A Phase I, Single and Multiple Dose Escalation/Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics, Food Effect, and Preliminary Antitumor Activities of BGB-283 in Chinese Subjects With Local Advanced or Metastatic Malignant Solid Tumor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Stage 3: Detect Ka for Pop-PK analysis
研究概览
简要总结
This study will evaluate the safety, tolerability, pharmacokinetics, food effect, and preliminary antitumor activities of BGB-283 in Chinese subjects with local advanced or metastatic malignant solid tumor.
详细描述
"This study is conducted on the basis of the completed multi-dose, dose escalation, Phase IA trial in Australia, is a dose-finding, dose expansion and food effects study of BGB-283 capsules in Chinese patients with locally advanced or metastatic solid tumor to determine the tolerability, safety, pharmacokinetic profiles, preliminary efficacy, food effects under high-fat meal on the absorption and metabolism of BGB-283, and preliminary anti-tumor efficacy.
The study was conducted in three phases: Stage I for dose escalation, Stage II for dose expansion and Stage III for food effects on pharmacokinetics under high fat meal.
Stage I Dose escalation: In a open-label, dose-escalation design, dose escalation will be performed with the '3 + 3' scheme and the dosage levels of BGB-283 capsules will be gradually increased.
Stage II Dose expansion: 20 mg/qd and 30 mg/qd are considered as effective and safe doses, based on preliminary results from Phase IA clinical studies in Australia. To further understand the preliminary pharmacodynamic results of BGB-283 in Chinese patients with malignant melanoma, 20mg/qd dose expansion study in B-RAF mutated malignant melanoma will be further explored if it has been proved to be a safe dose in Chinese population according to the '3 + 3' scheme.
Stage III uses multi-center, open, two-group crossover self-control design to compare the high-fat meal effect on pharmacokinetics."
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provided written informed consent prior to enrollment.
- •Male or female and between 18 and 75 years old.
- •A life expectancy of more than 12 weeks.
- •Stage I and III: Histologically or cytologically confirmed advanced or metastatic solid tumor for which no effective standard therapy is available. We simultaneously require patients with one of B-RAF, N-RAS, or K-RAS mutation positive solid tumor.
- •In Stage II: we require advanced or metastatic melanoma with the B-RAF mutation.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Able to swallow and retain oral medication.
- •Adequate bone marrow, liver, and renal function:
- •Hemoglobin > 90 g/L
- •Absolute neutrophil count ≥ 1.5x10^9/L
- •Platelets ≥ 100 x10^9/L
- •Total bilirubin ≤1.5 times the upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with known liver metastasis)
- •Creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft Gault formula).
排除标准
- •Female subjects who are pregnant or lactating.
- •Prior chemotherapy, radiotherapy, immunotherapy or any investigational therapies used to control cancer must have been completed at least 4 weeks or at least 5 half-lives (whichever is shorter before study drug administration, but at least 21 days)
- •Any major surgery within 28 days prior to enrollment.
- •Any radiotherapy for metastatic foci within 14 days prior to enrollment,
- •Unresolved toxicity > Grade 1 (according to NCI-CTCAE, Version 4.03) from previous anti cancer therapy.
- •History or presence of gastrointestinal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- •Any clinical significant active infection that need systematic treatment, including HIV positive subjects, or known Hepatitis B or C.
研究组 & 干预措施
Stage I
Approximately 25-35 Chinese subjects with local advanced or metastatic malignant solid tumor will be enrolled in the dose escalation stage of BGB-283 until maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) determination
干预措施: BGB-283 (Drug)
Stage II
Approximately 15-30 melanoma subjects will be enrolled in dose expansion stage of BGB-283
干预措施: BGB-283 (Drug)
Stage III
20 subjects will be enrolled for food effect stage of BGB-283
干预措施: BGB-283 (Drug)
结局指标
主要结局
Stage 3: Detect Ka for Pop-PK analysis
时间窗: Within 43 days since first dose
Stage 1: Number of participants with treatment-related adverse events as assessed by CTC AE 4.03, 1 year in average
时间窗: From signing the informed consent form and throughout the study, 1 year in average
Stage 2: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1
时间窗: Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, 1 year in average
Stage 3: Area under the plasma concentration-time curve from time 0 to infinity time (AUC)
时间窗: Within 43 days since first dose
Stage 3: Maximum plasma concentration (Cmax)
时间窗: Within 43 days since first dose
Stage 3: Terminal elimination half-life (t1/2)
时间窗: Within 43 days since first dose
Stage 3: Detect CL/F for Pop-PK analysis
时间窗: Within 43 days since first dose
Stage 3: Detect Vc/F for Pop-PK analysis
时间窗: Within 43 days since first dose
次要结局
- Stage 1: Area under the plasma concentration-time curve from time 0 to infinity time (AUC)(Within 43 days since first dose)
- Stage 1: Maximum plasma concentration (Cmax)(Within 43 days since first dose)
- Stage 1: Terminal elimination half-life (t1/2)(Within 43 days since first dose)
- Stage 1: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1(Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, 1 year in average)
- Stage 2: Number of participants with treatment-related adverse events as assessed by CTC AE 4.03, 1 year in average(From signing the informed consent form and throughout the study, 1 year in average)
- Stage 3: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1(Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, 1 year in average)