A PHASE I/II DOSE FINDING AND EFFICACY STUDY OF THE TUMOUR TARGETING HUMAN 131I-L19SIP MONOCLONAL ANTIBODY IN PATIENTS WITH CANCER
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 34
- 试验地点
- 4
- 主要终点
- Phase I: Maximum tolerated dose (MTD)
研究概览
简要总结
The aim of this Study Protocol is to provide a basis for the clinical development of 131I-L19SIP as an anti-cancer therapeutic agent, following the promising results of a Phase I study.
详细描述
The L19SIP antibody is a fully human antibody, capable of preferential localization around tumor blood vessels while sparing normal tissues. The formation of new blood vessels is a rare event in the adult (exception made for the female reproductive cycle), but is a pathological feature of most aggressive types of cancer. The study aims at determining the therapeutic potential of the L19SIP antibody in SIP format, labelled with the radionuclide 131I, for the treatment of patients with different cancer types. The study follows a Phase I study performed with 131I-L19SIP in over 30 patients with cancer, which has shown an excellent tolerability at radioactive doses as high as 150 mCi and therapeutic benefit for some patients enrolled in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with cancer, with progressive disease in pre-study period, refractory to conventional standard treatments.
- •Histologically/cytologically confirmed diagnosis of cancer, preferably lung cancer, prostate cancer and colorectal cancer (CRC). At least one measurable (minimum 2.0 cm), non irradiated lesion defined according to modified RECIST criteria, i.e. whenever the measurable disease is restricted to a solitary lesion, its neoplastic nature need not to be confirmed by cytology/histology.
- •ECOG performance status grade 0 or
- •Age ≥18 and ≤ 75 years.
- •Adequate haematological, liver and renal function (haemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1.50 x 10^9/L; platelets ≥ 100 x 10^9/L, bilirubin within UNL; alkaline phosphatase≤ 2.5 x UNL; ALT, AST ≤ UNL or ≤ 2.5 x UNL in case of liver metastases; albumin ≥ 2.5 g/dL; creatinine ≤ UNL.
- •All acute toxic effects (excluding alopecia) of any prior therapy (including surgery radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v.3.0) Grade ≤
- •Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment.
- •If of childbearing potential, agreement to use adequate contraceptive methods (e.g. oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug.
- •Evidence of a personally signed and dated IEC-approved Informed Consent indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study.
- •Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
- •Life expectancy of at least 3 months.
- •Signed and dated informed consent.
排除标准
- •Chemotherapy, radiation, hormonotherapy (with the exception of a gradual titration of LHRH agonists) or immunotherapy or participation in any investigational drug study within 4 weeks of study entry (6 weeks in case of prior nitroureas chemotherapy).
- •Prior radiation dose > 30% of bone marrow volume.
- •Presence of cirrhosis or active hepatitis.
- •Presence of serious cardiac (congestive heart failure, heart insufficiency > grade II NYHA, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorders.
- •Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
- •Recovery from major trauma including surgery within 4 weeks of administration of study treatment.
- •Pregnancy or lactation or unwillingness to use adequate method of birth control.
- •Active infection or incomplete wound healing.
- •Known history of allergy to intravenously administered proteins / peptides / antibodies.
- •Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
研究组 & 干预措施
L19SIP I131
Phase I: Multicentre, open-label, two-step single-arm dose escalation study in sequential cohorts of patients with cancer.
Phase II: Prospective, open-label, single-arm, multicentre study of 131I-L19SIP, given at the RD as determined in phase I.
干预措施: 131I-L19SIP Radioimmunotherapy (RIT) (Drug)
结局指标
主要结局
Phase I: Maximum tolerated dose (MTD)
时间窗: 4 weeks
Establishment of the maximum tolerated dose (MTD) and the recommended dose (RD) for the radiolabelled L19SIP monoclonal antibody.
Phase II: Antitumour activity
时间窗: 1- 14 months
Investigation of the antitumour activity of 131I-L19SIP at the RD, in patients with advanced cancer.
次要结局
- Phase I: Study of the variation of radioactivity of 131I in whole blood, at several time intervals (Pharmacokinetics)(2 days)
- Phase II: Safety profile(30 days/ administration)
- Phase II: Overall Response Rate (ORR)(6 and 12 months)
- Phase II: Progression free survival (PFS)(6 and 12 months)
- Phase II: Survival rate(6 and 12 months)