A Phase I/II, Open-Label, Single-Arm Study on Safety, Tolerability and Anti-Tumour Efficacy of Orellanine Treatment in Patients With Metastatic Clear-Cell or Papillary Renal Cell Carcinoma

Oncorena AB10 个研究点分布在 5 个国家目标入组 75 人开始时间: 2023年8月4日最近更新: 2026年9月9日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: Oncorena AB
入组人数: 75
试验地点: 10
主要终点: Changes in arterial blood pressure measurements

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

A phase I/II, open-label, study to determine the safety and preliminary efficacy of orellanine in patients with metastatic clear-cell or papillary renal carcinoma who have failed standard-of-care therapy. All participants must have end-stage kidney disease and be receiving stable chronic hemodialysis.

详细描述

This is an open, non-controlled, phase I/II study evaluating the safety, tolerability, and anti-tumor efficacy of orellanine treatment in patients with metastatic clear-cell or papillary renal carcinoma. The study will include up to 75 patients and is conducted in 3 parts. The study will consist of 3 parts: Part A - an intra-patient dose escalation part, followed by a dose exposure (Part B), followed by a dose expansion (Part C).

Part A, which is now closed, used an intra patient dose escalation design to evaluate safety across multiple dose levels.

The study is currently in Part B, an exposure based dose escalation phase. Patients may be enrolled into either a 24 hour or a 72 hour exposure cohort. Exposure duration is defined by the timing of hemodialysis, as elimination of orellanine occurs primarily through dialysis initiated after infusion. The starting dose for Part B is 0.38 mg/kg, and the total dose per treatment cycle is limited to 2.5 mg/kg, including any replacement doses. A minimum of three patients will be enrolled in each cohort, and escalation to longer exposure durations occurs only after safety evaluation.

Part C is a planned dose expansion phase to further characterize safety and explore preliminary antitumor activity at the selected dose and exposure level.

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

•Has provided written informed consent.
•Has a diagnosis of histologically confirmed advanced ccRCC or pRCC. No conventional therapy is available or considered appropriate by the treating physician or is declined by the patient.
•For patients in the expansion portion of the study only: Measurable disease per RECIST version 1.1 criteria.
•ECOG performance status of 0 -
•Age ≥18 years.
•Life expectancy ≥3 months.
•Has acceptable haematologic laboratory values defined as:
•Neutrophils ≥1.5 × 10^9/L, without growth factor stimulation within 3 weeks prior to the blood test;
•Platelets ≥100 × 10^9/L;
•Haemoglobin ≥5.6 mmol/L (~90 g/L). Use of erythropoietin or blood transfusions are permitted.
•Has acceptable liver laboratory values defined as:
•Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for patients with liver metastases
•Total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 × ULN
•For patients diagnosed with Gilbert's syndrome, total bilirubin ≤2 × ULN is acceptable.
•Must be on chronic hemodialysis (on a consistent regimen for the previous three months, with allowance for intermittent treatments as required for volume overload).
•The patient's treating nephrologist and oncologist agree that the prospect of loss of remaining renal function resulting from this treatment will not significantly change the patient's future and chronic dialysis treatment.
•Female patients of child-bearing potential and male patients must agree to use 2 forms of highly effective contraception for the duration of study treatment and after the last dose of orellanine for at least 3 months for males and 6 months for females.
•For females of child-bearing potential, a negative serum pregnancy test at screening.
•Patients who are willing and able to comply with travel requirements, scheduled visits, treatment schedule, efficacy assessments, laboratory tests, and other study procedures.

排除标准

•Diagnosis of any other malignancy within 2 years prior to enrolment, except for adequately treated basal cell or squamous cell skin cancer, superficial melanoma, or carcinoma in situ of the breast or of the cervix, or low grade (Gleason 7 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g., surgery, radiation, or castration)
•Radiotherapy within 2 weeks before first dose.
•Immuno-oncology therapy (IO) given in the last six (6) months prior to enrolment
•Other systemic anti-cancer therapy within 2 weeks before first dose.
•Has not recovered from AEs due to prior anti-cancer medications to at least grade 1 by CTCAE version 5.0 (except for alopecia and grade 2 neuropathy).
•Has received any other investigational product within 4 weeks before first dose.
•Pregnant or breastfeeding women.
•Uncontrolled medical condition including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, or would, in the opinion of the investigator, place the patient at increased risk.
•QTc interval at baseline of ≥470 msec.

研究组 & 干预措施

Part B - 72 Hour Exposure Cohort

Experimental

Participants receive orellanine (ONC175) as a 30 minute intravenous infusion once during each 28 day treatment cycle. In this cohort, hemodialysis is performed on the morning of the infusion, and additional hemodialysis sessions occur on the following days. Replacement doses of orellanine may be administered on the days after the initial infusion, depending on the assigned dose level. Hemodialysis is performed approximately 72 hours after the initial infusion to define the extended exposure period, as orellanine is eliminated primarily through dialysis.

干预措施: Orellanine (Drug)

Part B - 24-Hour Exposure Cohort

Experimental

Participants receive orellanine (ONC175) as a 30 minute intravenous infusion once during each 28 day treatment cycle. Hemodialysis is performed the day before the infusion and again approximately 24 hours after the infusion to define the exposure period, as orellanine is eliminated primarily through dialysis. Participants will continue their regular hemodialysis schedule throughout the cycle.

干预措施: Orellanine (Drug)