Phase 1 Study of the Anti-VEGFR-3 Monoclonal Antibody IMC-3C5 in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy is Available
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 4
- 主要终点
- Number of Participants Reporting Dose-Limiting Toxicity (DLT)
研究概览
简要总结
A dose escalation study to determine the safety and maximum tolerated dose (MTD) of IMC-3C5 in subjects with advanced solid tumors that are refractory to standard therapy or for which no standard therapy is available.
详细描述
This multicenter study will enroll approximately 40 participants. The actual sample size will vary depending on how many participants are needed to obtain at least 3 complete participants per cohort.
IMC-3C5 will initially be administered once every week (Cohorts 1-4) in a dose escalated manner. The starting dose will be 5 mg/kg weekly (Cohort 1). Dose escalation will proceed to 10 mg/kg (Cohort 2), 20 mg/kg (Cohort 3), and 30 mg/kg (Cohort 4). Based on an analysis of the safety and pharmacokinetic profile of weekly dosing, participants may be enrolled sequentially into 2 every-other-week dose cohorts (Cohorts 5-6, 20 mg/kg and 30 mg/kg). Intermediate doses may also be used.
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
- •Participant has histologic or cytologic confirmation of cancer
- •Participant has an advanced solid tumor that is refractory to standard therapy or for which no standard therapy is available
- •Participant has measurable or nonmeasurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- •Participant has not received prior chemotherapy or prior treatment with an investigational agent or device within 28 days prior to enrollment(hormone therapy is acceptable)
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2
- •Participant has adequate hematologic, hepatic, renal, and coagulation function
- •Participant has a life expectancy greater than 3 months
- •Participant agrees to use adequate contraception during the study period and for 12 weeks after last dose of investigational agent
排除标准
- •Participant has a known sensitivity to monoclonal antibodies or other therapeutic proteins, or to agents of similar biologic composition as IMC-3C5
- •Participant has received treatment with any monoclonal antibodies including bevacizumab within 6 weeks prior to enrollment
- •Participant has undergone a major surgical procedure, radiation therapy, open biopsy, or has experienced a significant injury within 28 days prior to enrollment
- •Participant has an ongoing or active infection (except as outlined in Exclusion Criterion #11), congestive heart failure, active bleeding or any other serious uncontrolled medical disorder
- •Participant has known or suspected untreated brain or leptomeningeal metastases
- •Participant has uncontrolled hypertension
- •Participant has received an organ transplant
- •Participant has a serious or nonhealing wound, ulcer, or bone fracture
- •Participant has experienced an arterial or venous thromboembolic event within 6 months prior to enrollment
- •Participant currently has peripheral edema requiring diuresis or anasarca
- •Participant has Human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), except subjects who have been on a stable antiviral regimen for at least 12 weeks, have a viral load of < 50 copies/mL, and a CD4 count of ≥ 200 cells/mm3
- •Participant is currently using or has received a thrombolytic agent within 28 days prior to enrollment
- •Participant is receiving aspirin at a dose higher than 325 mg per day or full-dose anticoagulation
- •Participant if female, is pregnant or is lactating
研究组 & 干预措施
IMC-3C5
Participants receiving IMC-3C5 intravenously
干预措施: IMC-3C5 (Biological)
结局指标
主要结局
Number of Participants Reporting Dose-Limiting Toxicity (DLT)
时间窗: Baseline up to 16 Months
A DLT was defined as any adverse event (National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\], Version 4.0) considered by the investigator to be definitely, probably, or possibly related to IMC-3C5, that occurred during the DLT Assessment Period (weeks 1 through 6) as follows: * Any Grade 3 or 4 hematologic toxicity * Any Grade 3 or 4 nonhematologic toxicity (excluding fatigue or anorexia lasting \<7 days, or Grade 3 nausea and/or vomiting that persisted for \<2 days following appropriate supportive care intervention)
Number of Participants With Adverse Events (AEs)
时间窗: Baseline up to 46 months
AEs include serious AEs (SAEs). AEs do not distinguish whether the events are treatment-emergent. A summary of serious and other non-serious AEs, regardless of causality, is presented in the Reported Adverse Event module.
次要结局
- Maximum Concentration (Cmax) of IMC-3C5 - First Infusion(Prior to 1st infusion (Day 1 of Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168 hours post infusion for cohorts 1-4. Prior to 1st infusion and 1 hour post infusion for cohort 5. (Cycle 1 = 4 - 6 weeks.))
- Anti-IMC-3C5 Antibody Assessment(Predose: First and fourth infusions (Cycle 1), ninth infusion (Cycle 3), 15th infusion (Cycle 4), 21st infusion (Cycle 6), 27th infusion (Cycle 7). (Cycle 1 = 4 - 6 weeks. Subsequent cycles = 4 weeks.))
- Antitumor Activity of Single Agent IMC-3C5: Best Overall Response (BOR)(Baseline up to 46 Months)
- Terminal Half-life (t1/2) of IMC-3C5 - Fourth Infusion(Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.))
- Volume of Distribution of IMC-3C5 at Steady State (Vss) - Fourth Infusion(Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.))
- Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Drug Concentration (AUC 0-tlast) of IMC-3C5 - First Infusion(Prior to 1st infusion (Day 1 of Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.))
- Area Under the Concentration-Time Curve During One Dose Interval (AUCtau) of IMC-3C5 (168 Hours) - Fourth Infusion(Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.))
- Maximum Concentration (Cmax) of IMC-3C5 - Fourth Infusion(Prior to 4th infusion (approximately Day 22, Cycle 1), immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. Prior to 4th infusion, 1 hour post infusion for cohort 5. (Cycle 1 = 4-6 weeks.))
- Clearance (Cl) of IMC-3C5 at Steady State - Fourth Infusion(Prior to 4th infusion (approximately Day 22) of Cycle 1, immediately after, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264, 336, 504 hours post infusion for cohorts 1-4. (Cycle 1 = 6 weeks.))
- Minimum Concentration (Cmin) of IMC-3C5 - Fourth Infusion(Prior to 4th infusion (approximately Day 22) of Cycle 1 for cohorts 1-5. (Cycle 1 = 4 - 6 weeks.))