An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is an Open-Label, Multicenter, Dose Escalation, First-in-Human Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase C.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary consent form
- •Diagnosis of GI malignancy with a GCC protein expressing tumor
- •Male or female patients 18 years or older with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
- •Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
- •Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate bone marrow, hepatic and renal function as specified in the protocol
排除标准
- •Female patients who are lactating or have a positive serum pregnancy test during the screening period
- •Any serious medical or psychiatric illness that could interfere with the completion of treatment
- •Major surgery or treatment with investigational drug before the first dose
- •Serious infection within 14 days before the first dose of study drug
- •Known HIV, inflammatory bowel disease, viral hepatitis or cerebral/meningeal brain metastases
- •Patients with cardiovascular conditions specified in protocols
- •Patients with history of another primary malignancy not in remission for at least 3 years
- •Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
- •Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons.
研究组 & 干预措施
MLN0264
MLN0264 starting dose 0.3 mg/kg escalated until Maximum Tolerated Dose (MTD) was determined, 30-minute infusion, on Day 1 of each 21-Day treatment cycle.
干预措施: MLN0264 (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months
DLT was defined as any of the following Adverse Events (AEs) that occur and are considered by the investigator to be related to therapy. 1. Grade 4 neutropenia (Absolute Neutrophil Count \< 500 cells/mm\^3). 2. Grade 3 or greater neutropenia with fever and/or infection. 3. Grade 4 thrombocytopenia (platelets \< 25,000/mm\^3). 4. Grade 3 or greater thrombocytopenia with clinically meaningful bleeding at any time. 5. Grade 3 or greater nausea and/or emesis that occurs despite of prophylaxis. 6. Grade 3 or greater diarrhea that occurs despite supportive care. 7. Any other Grade 3 or greater non-hematological toxicity other than Grade 3 fatigue or Grade 3 Alopecia. 8. Inability to start the next cycle of therapy due to treatment delay of more than 2 weeks because of lack of recovery. 9. Other MLN0264-related non-hematologic toxicities Grade 2 or greater requiring discontinuation of therapy.
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
时间窗: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Maximum Tolerated Dose (MTD) of MLN0264
时间窗: Every 3 weeks until MTD is established, approximately 9 months
MTD of MLN0264 was determined. Decisions regarding dose escalation were made based on any DLT that occurred during the first cycle of treatment.
Cmax: Maximum Observed Serum Concentration for MLN0264
时间窗: Cycle 1: Day 1 pre-dose to Day 21 post-dose
Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably.
Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)
时间窗: Cycle 1: Day 1 pre-dose to Day 21 post-dose
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably.
AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MLN0246
时间窗: Cycle 1: Day 1 pre-dose to 21 Days post-dose
Area under the drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably.
AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MMAE
时间窗: Cycle 1: Day 1 pre-dose to 21 Days post-dose
Area under the plasma drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably.
次要结局
- Best Overall Response(At the completion of every second cycle up to 12 cycles (approximately 9 months). Each cycle is a 21 days cycle)
- Number of Participants With Antitherapeutic Antibodies (ATA)(Day 1 of every 21 days cycle and at End of study (EOS) approximately 9 months)