A Phase I/II Study of Once or Twice Weekly IMMU-130 (hMN-14-SN38, Antibody-Drug Conjugate) in Patients With Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 92
- 试验地点
- 7
- 主要终点
- Percentage of Participants With Adverse Events and Serious Adverse Events (SAEs)
研究概览
简要总结
The goal of this clinical study is to determine the dosing and safety of labetuzumab govitecan (formerly known as IMMU-130; hMN-14-SN38, antibody-drug conjugate) in participants with colorectal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histologically or cytologically confirmed colorectal adenocarcinoma.
- •Stage IV (metastatic) disease.
- •Previously treated with at least one prior irinotecan-containing regimen for colorectal cancer.
- •Adequate performance status (Eastern Cooperative Oncology Group (ECOG) 0 or 1).
- •Expected survival > 6 months.
- •Carcinoembryonic antigen (CEA) plasma levels > 5 ng/mL.
- •Measurable disease by computed tomography (CT) or Magnetic resonance imaging (MRI).
- •At least 4 weeks beyond treatment (chemotherapy, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities.
- •At least 2 weeks beyond corticosteroids.
- •Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, absolute neutrophil count (ANC) > 1,500 per mm^3, platelets > 100,000 per mm^3).
- •Adequate renal and hepatic function (creatinine ≤ 1.5 x IULN, bilirubin ≤ institutional upper limit of normal (IULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x IULN or 5 x IULN if know liver metastases).
- •Otherwise, all toxicity at study entry ≤ Grade 1 by National cancer institute common terminology criteria for adverse events (NCI CTC) v4.0.
排除标准
- •Women who are pregnant or lactating.
- •Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.
- •Individuals with Gilbert's disease or known central nervous system (CNS) metastatic disease.
- •Individuals with CEA plasma levels > 1000 ng/mL must be approved in advance by the Sponsor.
- •Presence of bulky disease (defined as any single mass > 10 cm in its greatest dimension).
- •Individuals with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
- •Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while individuals with other prior malignancies must have had at least a 3-year disease-free interval.
- •Individuals known to be human immunodeficiency virus (HIV) positive, hepatitis B positive, or hepatitis C positive.
- •Known history of unstable angina, myocardial infarction, or congestive heart failure present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
- •Known history of clinically significant active chronic obstructive pulmonary disease (COPD), or other moderate-to-severe chronic respiratory illness present within 6 months.
- •Infection requiring intravenous antibiotic use within 1 week.
- •Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
研究组 & 干预措施
Phase1: Dose-escalation Phase: Labetuzumab Govitecan (LG) Once Weekly Dosing
Participants will receive 8, 12 and 16 mg/dose of LG once weekly dosing until unacceptable toxicity, progressive disease or death whichever occurs first, for each 21-day cycle for up to up to 8 cycles, with a contingency to examine intermediate dose levels of 10 or 14 mg/kg, or if necessary to a lower dose level of 6 mg/kg.
干预措施: Labetuzumab Govitecan (LG) (Drug)
Phase1: Dose-escalation Phase: LG Twice Weekly Dosing
Participants will receive 6 and 9 mg/kg per dose twice weekly dose of LG until unacceptable toxicity, progressive disease or death whichever occurs first, for each 21-day cycle for up to up to 8 cycles. A lower dose level of 4 mg/kg may be added if > 1 out of 3 or 2 out of 6 participants are unable to tolerate all 4 doses without dose delay or reduction.
干预措施: Labetuzumab Govitecan (LG) (Drug)
Phase 2: Dose-expansion Phase: LG Once or Twice Weekly Dosing
Participants will receive selected doses of LG once or twice weekly until unacceptable toxicity, progressive disease or death whichever occurs first, for each 21-day cycle for up to 8 cycles.
干预措施: Labetuzumab Govitecan (LG) (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events and Serious Adverse Events (SAEs)
时间窗: From first dose date up to approximately 2 years after the last dose or until disease progression
Percentage of Participants With Laboratory Abnormalities
时间窗: From first dose date up to approximately 2 years after the last dose or until disease progression
次要结局
- Progression-free Survival(From first dose date up to 12 weeks post treatment (Up to approximately 2 years after the last dose or until disease progression))
- Change from Baseline in Carcinoembryonic Antigen (CEA) Serum Levels(From first dose date up to approximately 2 years after the last dose or until disease progression)
- Duration of Response(From first documentation of PR or CR to the earlier of the first documentation of PD or death from any cause (Up to approximately 2 years after the last dose or until disease progression))
- Time-to-treatment Failure(From first dose date up to 8 treatment cycles (each cycle = 21 days) (Up to approximately 24 weeks))
- Time to Progression(From first dose of study treatment up to PD (Up to approximately 2 years after the last dose or until disease progression))
- Overall Survival(From first dose date up to approximately 2 years)