A Phase I/II Dose Finding and Efficacy Study of the Tumour Targeting Human 131I-F16SIP Monoclonal Antibody in Patients With Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 65
- 试验地点
- 6
- 主要终点
- Phase I: Maximum tolerated Dose
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-F16SIP as an anti-cancer therapeutic agent.
The study follows and is greatly motivated by the promising results of a Phase I/II study with a similar investigational drug developed by our Company, 131I-L19SIP, in several Italian centers.
详细描述
The F16SIP antibody is a fully human antibody, capable of preferential localization around tumour 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 F16 antibody in SIP format,labelled with the radionuclide 131I, for the treatment of patients with different cancer types.
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 —（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.
- •Solid Tumor: Histologically/cytologically confirmed diagnosis of cancer, preferably lung cancer, prostate cancer or 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 be confirmed by cytology/histology.
- •Lymphoproliferative Diseases: Histologically/cytologically confirmed diagnosis of lymphoproliferative disease. 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 needs to be confirmed by cytology/histology.
- •Patients with lymphoma, breast cancer or lung cancer with progressive disease in pre-study period, refractory to conventional standard treatments, will be enrolled in the study. Presence of brain metastases at time of screening does not represent an exclusion criterion. Lesions will be evaluated according to RECIST for solid tumors or to the Revised response criteria for malignant lymphoma (Cheson BD, JCO 2007, 25, 579-58) for lymphomas.
- •ECOG performance status grade 0 or
- •Adequate haematological, liver and renal function (haemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1.50 x 109/L; platelets ≥ 100 x 109/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 or immunotherapy or participation in any investigational drug study within 4 weeks of RIT treatment at the RD (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
I131-F16SIP
Phase I: Multicentre, open-label, two-step singlearm dose escalation study in sequential cohorts of patients with cancer.
Phase II: Prospective, open-label, single-arm, multicentre study of 131I-F16SIP, given at the RD of 55.5 mCi/m2, as determined in phase I.
干预措施: 131I-F16SIP Radioimmunotherapy (RIT) (Drug)
结局指标
主要结局
Phase I: Maximum tolerated Dose
时间窗: 4 weeks
Establishment of the maximum tolerated dose (MTD), a recommended dose (RD) for the phase II part, and the safety of dosimetric and therapeutic administration of escalating dosages of the human radiolabeled antibody 131I-F16SIP.
Phase II: Antitumour activity
时间窗: 14 months
Investigation of the antitumour activity of 131I-F16SIP at the RD.
次要结局
- Phase I: Study of the variation of radioactivity of 131I or 124I in whole blood, at several time intervals (Pharmacokinetics)(2 days)
- Phase II: Adverse Events as a Measure of Safety(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)