A Multiple Dose, Dose Escalation Trial of AEB1102 (Co-ArgI-PEG) in Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- Co-ArgI-PEG
- 疾病 / 适应症
- Advanced Cancers
- 发起方
- Aeglea Biotherapeutics
- 入组人数
- 98
- 试验地点
- 11
- 主要终点
- maximum tolerated dose
- 状态
- 已完成
- 最后更新
- 4年前
概览
简要总结
This is the first-in-human study of the safety of increasing dose levels of AEB1102 in patients with advanced cancers. The study will also evaluate the amounts of AEB1102 in blood, the effects of AEB1102 on blood amino acid levels and tumor growth.
详细描述
In this phase I/2 multiple dose, dose escalation study utilizing a classic 3+3 design. Sequential cohorts of patients will receive AEB1102 IV weekly at one of a series of increasing dose levels. Dose escalation will be dependent on the frequency of specific dose-limiting toxicities in the prior cohort of patients. The study will determine the maximum tolerated dose (MTD) of AEB1102, evaluate the safety profile of the compound, assess the pharmacokinetic profile of AEB1102, determine the effect of AEB1102 on blood arginine levels and evaluate the anti-tumor activity of AEB1102. Following the determination of the MTD, additional cohorts of patients with uveal, cutaneous melanoma and small cell lung cancer will be enrolled and treated with AEB1102 at the MTD.
研究者
入排标准
入选标准
- •For patients participating in any part of the trial:
- •has an advanced solid tumor previously treated with, or inability to tolerate, standard therapy for the disease, or for which a standard therapy does not exist, and as such is considered a candidate for Phase 1 treatment
- •has adequate organ function: Hgb ≥9 g/dL; absolute neutrophil count (ANC) ≥ 1.5x109/L; plt ≥ 100,000/μL; AST and ALT \< 2.5x ULN (\< 5x ULN in patients with liver metastases); total bilirubin \< 2.0 mg/dL; serum creatinine ≤ 1.5x ULN
- •ECOG performance score 0-2
- •For patients participating in any expansion group:
- •has measurable disease based on RECIST 1.1 as determined by the treating investigator. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- •willing to consent for biopsy is strongly recommended but not mandatory
- •recovery of toxicities related to any prior treatments to at least Grade 1 by CTCAE v 4.
- •Exceptions are patients with adverse event(s) that are clinically nonsignificant and/or stable on supportive therapy.
- •For patients participating in specific expansion groups:
排除标准
- •has primary CNS malignancy
- •history of untreated brain mets or leptomeningeal disease or spinal cord compression
- •effects of prior anticancer therapy recovered to grade \< 2
- •known HIV
- •active infection
- •major surgery within 2 weeks
- •history of another malignancy within 2 years prior
研究组 & 干预措施
AEB1102 Dose Escalation Cohort 1
3 patients dosed at 0.01 mg/kg until MTD determined
干预措施: Co-ArgI-PEG
AEB1102 Dose Escalation Cohort 2
4 patients dosed at 0.02 mg/kg until MTD determined
干预措施: Co-ArgI-PEG
AEB1102 Dose Escalation Cohort 3
4 patients dosed at 0.04 mg/kg until MTD determined
干预措施: Co-ArgI-PEG
AEB1102 Dose Escalation Cohort 4
4 patients dosed at 0.08 mg/kg until MTD determined
干预措施: Co-ArgI-PEG
AEB1102 Dose Escalation Cohort 5
3 patients dosed at 0.12 mg/kg until MTD determined
干预措施: Co-ArgI-PEG
AEB1102 Dose Escalation Cohort 6
4 patients dosed at 0.18 mg/kg until MTD determined
干预措施: Co-ArgI-PEG
AEB1102 Dose Escalation Cohort 7
5 patients dosed at 0.27 mg/kg until MTD determined
干预措施: Co-ArgI-PEG
AEB1102 Dose Escalation Cohort 8
7 patients dosed at 0.40 mg/kg until MTD determined
干预措施: Co-ArgI-PEG
AEB1102 Dose Escalation Cohort 9
7 patients dosed at 0.33 mg/kg until MTD determined MTD determined at 0.33 mg/kg
干预措施: Co-ArgI-PEG
AEB1102 Expansion
Uveal: 11 patients dosed at 0.33 mg/kg Cutaneous Melanoma: 11 dosed at 0.33 mg/kg SCLC: 13 patients dosed at 0.33 mg/kg
干预措施: Co-ArgI-PEG
结局指标
主要结局
maximum tolerated dose
时间窗: 4 weeks
the dose level at which no more than 1/6 patients experiences dose-limiting toxicity
次要结局
- safety profile (changes in physical exam, laboratory measures, reported adverse events)(4 weeks +)