An Open-Label, Dose Escalation Phase I Trial of MK-0646 Given as a One to Two Hour Every Other Week Infusion in Patients With Relapsed or Refractory Locally Advanced or Metastatic Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 主要终点
- Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs)
研究概览
简要总结
The study determined the recommended Phase 2 loading and maintenance doses and dose schedules for administering dalotuzumab using dose-limiting toxicities (DLTs) observed during the entire treatment period (Up to 18 months). The primary hypothesis of the study was that administration of dalotuzumab as an every other week infusion in participants with relapsed or refractory locally advanced or metastatic cancers associated with a high frequency of insulin-like growth factor receptor type 1(IGF-1R) overexpression will be generally safe and well tolerated to permit further study and achieve a constant clearance and a minimum trough concentration of 3 µg/mL.
详细描述
The study consisted of 3 parts. In Part 1 the loading dose was escalated while the maintenance dose was kept constant. In Part 2 the loading dose was kept constant while the maintenance dose was escalated. In Part 3 the recommended phase 2 loading and maintenance doses and schedule were administered to an expanded cohort to explore safety and efficacy of dalotuzumab.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females with advanced solid tumors who have failed to respond to standard therapy, ages 18 years and older, with adequate organ function
排除标准
- •Participant is using growth hormones or growth hormone inhibitors
- •Participant is known to be allergic to components of the drug or similar drugs (e.g. monoclonal antibodies such as rituximab or biological therapies such as immunoglobulin G
- •Participant has had chemotherapy, radiotherapy, or biological therapy within 4-6 weeks of entering the study or has not recovered from previous therapy
- •Participant is taking part in or has taken part in a study of an investigational compound or device within 30 days of their first dose of study drug
- •Participant has an active Central Nervous System metastases and/or carcinomatous meningitis. However, a participant who has completed a course of therapy and is clinically stable may be able to participate
- •Participant is pregnant or breastfeeding
- •Participant is human immunodeficiency virus (HIV) positive
- •Participant has a history of Hepatitis B or C
- •Participant has symptomatic ascites or pleural effusion. However, if the participant has received treatment and is stable, they may be able to participate
- •Female participant plans to become pregnant or a male participant who plans to impregnate their partner during the time the study is ongoing
研究组 & 干预措施
dalotuzumab 2.5/2.5 mg/kg
Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by intravenous (IV) infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.
干预措施: dalotuzumab (Drug)
dalotuzumab 5.0/5.0 mg/kg
Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
干预措施: dalotuzumab (Drug)
dalotuzumab 10.0/5.0 mg/kg
Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
干预措施: dalotuzumab (Drug)
dalotuzumab 15.0/5.0mg/kg
Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
干预措施: dalotuzumab (Drug)
dalotuzumab 20.0/5.0 mg/kg
Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
干预措施: dalotuzumab (Drug)
dalotuzumab 15.0/10.0 mg/kg
Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
干预措施: dalotuzumab (Drug)
dalotuzumab 15.0/15.0 mg/kg
Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
干预措施: dalotuzumab (Drug)
结局指标
主要结局
Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs)
时间窗: The entire treatment period (Up to 18 months)
Dose-limiting toxicities (DLT) were assessed and graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE). A DLT was defined as the occurrence of any of the following events, that were judged by the study investigator, to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever \>38.5 degrees Celsius; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity (except alopecia and inadequately treated diarrhea, nausea, and vomiting, and hyperglycemia lasting less than 5 days; and Grade 3 or greater hyperglycemia lasting for more than 5 days in spite of optimal medical management.
Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose
时间窗: 2 weeks post first maintenance dose of study drug (3 weeks post loading dose of study drug)
Blood samples were obtained for analysis of steady-state serum concentration of dalotuzumab at 336 hours (C336) after the first maintenance dose of dalotuzumab. The C336 of dalotuzumab after intravenous administration is presented.
次要结局
- Percent Change From Baseline in Serum Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Level at Week 1(Baseline and Week 1)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 5(Baseline and Week 5)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 9(Baseline and Week 9)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 25(Baseline and Week 25)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 37(Baseline and Week 37)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 41(Baseline and Week 41)
- Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)(Up to 18 months post first dose of study drug)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 33(Baseline and Week 33)
- Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer(Prior to second and subsequent doses of study drug (Up to 1 year post-first dose))
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 13(Baseline and Week 13)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 17(Baseline and Week 17)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 21(Baseline and Week 21)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 29(Baseline and Week 29)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 45(Baseline and Week 45)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 53(Baseline and Week 53)
- Percent Change From Baseline in Serum IGF-1R Protein Level at Week 49(Baseline and Week 49)