A Phase 1 Study to Evaluate the Dose, Safety and Tolerability of an Intraperitoneal α-emitting Radionuclide Therapy (Radspherin®) in Patients With Platinum Sensitive Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma With Peritoneal Carcinomatosis Following CRS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 4
- 主要终点
- Number of participants with Dose Limiting Toxicities as assessed by CTCAE v5.0.
研究概览
简要总结
RAD-18-001 is a First-In-Man, Dose Escalation study conducted at 2 sites. The dose escalation will be performed based on a 3 + 3 design. Increasing dose levels starting at 1 MBq will be followed by 2, 4 and 7 MBq. If the highest dose level of 7 MBq is reached without Dose Limiting Toxicicities (which will stop the dose escalation), this will be the recommended dose for further exploration. Each subject will be followed until disease progression (in the abdominal cavity), or for 24 months after the administration of Radspherin® (whichever comes first).
In the expansion cohort the subject will receive the recommended dose. The expansion cohort will be conducted at 4 sites. Each subject will be followed until disease progression (in the abdominal cavity), or for 24 months after the administration of Radspherin® (whichever comes first).
详细描述
The maximum number of subjects enrolled in this study is 49.
The following number of subjects will be recruited in the different cohorts:
- Dose escalation cohorts: 3 - 24 Subjects
- Expansion cohort: Up to 25 Subjects
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Able and willing to provide written informed consent and to comply with the clinical study protocol
- •Age ≥ 18 years
- •Histologically confirmed epithelial ovarian, fallopian tube and primary peritoneal carcinoma
- •Platinum sensitive recurrences of ovarian carcinoma who are eligible for debulking surgery to R
- •AEs recovered to at least grade 1 from the effects (excluding alopecia) of any prior medical therapy for malignancy at time of first administration of Radspherin®
- •ECOG Performance Status Score of 0 - 1
- •Adequate renal function
- •Creatinine ≤ 1.8 mg/dl (159 μmol/l) and
- •calculated creatinine clearance using the Cockcroft-Gault formula ≥ 45 ml/min, or
- •measured creatinine clearance ≥ 45 ml/min
- •Adequate hepatic function
- •Serum bilirubin <1.5 x upper limit of normal (ULN)
- •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
- •Adequate bone marrow function:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/l
- •Platelets ≥ 100 x 10^9/l
- •Haemoglobin ≥ 9 g/dL
- •Adequate coagulation tests: INR ≤ 1.5 x ULN
- •For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment
- •For females of childbearing potential who have a male partner: agreement to use two adequate methods of contraception (e.g. barrier, intrauterine device, hormonal implants, combined oral contraceptives or vasectomized partner), during the treatment period and for at least 3 months after the last dose of IMP.
排除标准
- •Neuroendocrine tumors, or non-epithelial ovarian cancers (e.g. germ cell tumors, Sex-cord tumors)
- •Tumors of borderline malignancy
- •Other synchronous visceral metastatic lesions, symptomatic CNS metastases. Metastatic lymph nodes are acceptable, except thoracic lymph nodes.
- •Pregnant or lactating (nursing) women
- •Active infections requiring antibiotics, and/or physician monitoring or recurrent fever >38.0 ⁰C associated with a clinical diagnosis of active infection
- •Active liver disease with positive serology for active hepatitis B, hepatitis C or known HIV
- •Administration of an investigational medicinal product within 28 days, or at least 5 times the half-life, prior to enrolment
- •Concurrent administration of any cancer therapy other than planned study treatment within 4 weeks prior to, and up to 4 weeks after the last study treatment
- •Another primary malignancy within the past 3 years (except for non-melanoma skin cancer, cervical cancer in situ or in situ stage 1 synchronous endometrial cancer)
- •Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease
- •Any condition or illness that, in the opinion of the Investigator or the medical monitor, would compromise the safety of the subjects or interfere with the evaluation of the safety of the IMP
- •In the Investigator's opinion not able to comply with study procedures. Any medical or psychological condition that would preclude participation in the study or compromise the ability to give informed consent
- •Treatment with bevacizumab (Avastin®) within 5 weeks prior to CRS
- •Known hypersensitivity to any of the excipients in the study drug
- •Persons who have been placed in an institution under an official or judicial order
- •Persons who are dependent on the sponsor financially must be excluded from participation
- •Persons with active SARS-CoV-2 infection must be excluded from participation
研究组 & 干预措施
Radspherin
干预措施: Radspherin (Drug)
结局指标
主要结局
Number of participants with Dose Limiting Toxicities as assessed by CTCAE v5.0.
时间窗: 24 months
To investigate safety and toxicity of Radspherin®
Maximum Tolerated Dose (MTD)
时间窗: 21 days
To determine the MTD of Radspherin®, among the four suggested doses 1, 2, 4 and 7 MBq, as a single intraperitoneal (IP) injection and two repeated IP injections following cytoreductive surgery (CRS)
次要结局
未报告次要终点