Phase I Trial of huA33 Plus 5-fluorouracil (5-FU), Leucovorin and Oxaliplatin in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Safety as Measured by the Number of Patients With Treatment Emergent Adverse Events (TEAEs), Grade 3 TEAEs, TEAEs Resulting in Death, TEAEs Related to Treatment and Serious TEAEs in Patients With Metastatic Colorectal Cancer.
研究概览
简要总结
Although treatment for metastatic colorectal cancer has improved significantly over the recent years, it still remains a significant health problem representing the leading cancer by incidence in the United States of America. In the search for new therapies, monoclonal antibodies have been developed to specifically target human colon cancer cells. huA33 is an antibody that reacts with the A33 antigen which is produced by colorectal cancers. Prior studies have shown that administration of the huA33 antibody may delay the growth of tumor cells producing the specific antigen. Oxaliplatin and 5-fluorouracil (5-FU) are cytotoxic agents which are considered as standard treatment in metastatic colorectal cancer. Leucovorin (folinic acid) is a vitamin which enhances the effect of 5-FU. Eligible patients with advanced colorectal cancer will receive huA33 10 mg/m2 by intravenous (IV) infusion weekly for twelve weeks. Starting on Study Day 15 (week 3), 5-FU, leucovorin, and oxaliplatin will be administered every 2 weeks for 10 weeks. Patients will be evaluated weekly for toxicity. Blood samples will be obtained every week for hematology and serum biochemistry analysis and for determination of human anti-human antibodies (HAHA). In patients with measurable disease, tumors will be assessed by the appropriate scan at baseline and at the end of the thirteen week cycle. The primary objective of this study is to assess the safety of huA33 + 5-FU + leucovorin + oxaliplatin. The secondary objective is to measure the immunogenicity of huA33 when given in combination with 5-FU plus leucovorin and oxaliplatin and to document tumor responses.
详细描述
Purpose of the Research Study:
huA33 is an antibody that reacts with the A33 antigen which is produced by colorectal cancers. Prior studies have shown that application of the huA33 antibody may delay the growth of tumor cells producing the respective antigen.
Oxaliplatin and 5-FU are cytotoxic agents which are considered as standard treatment in metastatic colorectal cancer. Leucovorin is a vitamin which enhances the effect of 5-FU.
The primary purpose of this study is to determine whether the combination huA33 plus oxaliplatin, 5-FU and leucovorin is safe and what side effects occur.
Description of Research Procedures:
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
- •Patients will be eligible for enrollment if they fulfill all of the following criteria:
- •Metastatic colorectal cancer.
- •Histologically or cytologically proven colorectal cancer.
- •Expected survival of at least 4 months.
- •Not more than 2 different pretreatment regimens.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Within the 2 weeks prior to the first dose of huA33, the following vital laboratory parameters:
- •Lab Parameter Range
- •Neutrophil count ≥ 1.5 x 10E9/L
- •Platelet count ≥ 150 x 10E9/L
- •Serum bilirubin ≤ 2 mg/dL
- •Creatinine clearance >50 ml/ min
- •Age ≥ 18 years.
- •Able and willing to give valid written informed consent.
排除标准
- •Patients will be excluded from the study for any of the following reasons:
- •Untreated active metastatic disease to the central nervous system defined as new or enlarging lesions on CT or MRI.
- •Surgery or radiotherapy of brain metastases within 3 months prior to the first dose of huA
- •Metastatic disease involving > 50% of liver volume.
- •Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.
- •Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing (6 weeks for nitrosoureas).
- •Previous treatment with oxaliplatin.
- •Previous treatment with huA33 monoclonal antibody or antibody fragment.
- •a. Positive huA33 HAHA titer - defined as greater than 3 standard deviations above the mean patient normal range by Biacore analysis.
- •Concomitant treatment with systemic corticosteroids. Topical or inhalational corticosteroids are permitted.
- •Known HIV, Hepatitis B or C positivity.
- •Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
- •Lack of availability of the patient for clinical and laboratory follow-up assessment.
- •Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing.
- •Pregnancy or breastfeeding.
- •Women of childbearing potential: Refusal or inability to use effective means of contraception.
研究组 & 干预措施
huA33 antibody plus chemotherapy
huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2 for 12 weeks.
Starting on day 15 and continuing every second week, oxaliplatin, 5-fluorouracil (5-FU) and leucovorin were also administered.
Oxaliplatin and leucovorin were given as infusions over 2 hours. Afterwards, patients received a bolus infusion of 5-FU intravenously followed by an infusion of 5-FU over 22 hours.
The doses of oxaliplatin were 85mg/m2, leucovorin 200mg/m2, 400mg/m2 of 5-FU as a bolus infusion and 600mg/m2 as a continuous infusion.
A complete treatment cycle consisted of 12 weeks. Patients were eligible to receive an additional cycle in the absence of dose-limiting toxicity (DLT), immunogenicity (huA33 human anti-human antibodies {HAHA}) and disease progression.
干预措施: Oxaliplatin (Drug)
huA33 antibody plus chemotherapy
huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2 for 12 weeks.
Starting on day 15 and continuing every second week, oxaliplatin, 5-fluorouracil (5-FU) and leucovorin were also administered.
Oxaliplatin and leucovorin were given as infusions over 2 hours. Afterwards, patients received a bolus infusion of 5-FU intravenously followed by an infusion of 5-FU over 22 hours.
The doses of oxaliplatin were 85mg/m2, leucovorin 200mg/m2, 400mg/m2 of 5-FU as a bolus infusion and 600mg/m2 as a continuous infusion.
A complete treatment cycle consisted of 12 weeks. Patients were eligible to receive an additional cycle in the absence of dose-limiting toxicity (DLT), immunogenicity (huA33 human anti-human antibodies {HAHA}) and disease progression.
干预措施: 5-Fluorouracil (Drug)
huA33 antibody plus chemotherapy
huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2 for 12 weeks.
Starting on day 15 and continuing every second week, oxaliplatin, 5-fluorouracil (5-FU) and leucovorin were also administered.
Oxaliplatin and leucovorin were given as infusions over 2 hours. Afterwards, patients received a bolus infusion of 5-FU intravenously followed by an infusion of 5-FU over 22 hours.
The doses of oxaliplatin were 85mg/m2, leucovorin 200mg/m2, 400mg/m2 of 5-FU as a bolus infusion and 600mg/m2 as a continuous infusion.
A complete treatment cycle consisted of 12 weeks. Patients were eligible to receive an additional cycle in the absence of dose-limiting toxicity (DLT), immunogenicity (huA33 human anti-human antibodies {HAHA}) and disease progression.
干预措施: Leucovorin (Drug)
huA33 antibody plus chemotherapy
huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2 for 12 weeks.
Starting on day 15 and continuing every second week, oxaliplatin, 5-fluorouracil (5-FU) and leucovorin were also administered.
Oxaliplatin and leucovorin were given as infusions over 2 hours. Afterwards, patients received a bolus infusion of 5-FU intravenously followed by an infusion of 5-FU over 22 hours.
The doses of oxaliplatin were 85mg/m2, leucovorin 200mg/m2, 400mg/m2 of 5-FU as a bolus infusion and 600mg/m2 as a continuous infusion.
A complete treatment cycle consisted of 12 weeks. Patients were eligible to receive an additional cycle in the absence of dose-limiting toxicity (DLT), immunogenicity (huA33 human anti-human antibodies {HAHA}) and disease progression.
干预措施: huA33 (Drug)
结局指标
主要结局
Safety as Measured by the Number of Patients With Treatment Emergent Adverse Events (TEAEs), Grade 3 TEAEs, TEAEs Resulting in Death, TEAEs Related to Treatment and Serious TEAEs in Patients With Metastatic Colorectal Cancer.
时间窗: up to 26 weeks
Patients were evaluated weekly for toxicity. Blood samples were obtained every week for hematology and serum biochemistry analysis. All adverse events, which occurred after the signing of informed consent were documented in the case report form. Toxicity was evaluated according to the National Cancer Institute CTCAE Scale (Version 3.0). All AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 13.1 and classified by MedDRA system organ class (SOC) and preferred term. Treatment emergent adverse events (TEAEs) are any adverse events occurring or worsening after the first administration of study drug.
次要结局
- Immunogenicity of huA33 as Measured by the Number of Patients With Human Anti-human Antibodies (HAHA) When Given huA33 Together With Oxaliplatin and 5-FU Plus Leucovorin in Patients With Metastatic Colorectal Cancer.(up to 26 weeks)
- Tumor Response in Patients With Metastatic Colorectal Cancer Receiving huA33, Oxaliplatin and 5-FU Plus Leucovorin.(up to 26 weeks)