Evaluation of ex Vivo Drug Combination Optimization Platform in Recurrent High Grade Astrocytic Glioma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Six-month progression-free survival (PFS 6)
研究概览
简要总结
This is an interventional, non-randomized, single site study. Brain tumor samples will be collected from patients for organoids generation and subject to panel drugs screening and QPOP analysis to derive the optimal drug combinations for treatment at the time of first high grade astrocytic glioma recurrence. The investigators hypothesize that patient-derived organoids (PDOs) mimic the biological characteristics of high grade astrocytic gliomas and serve as an ideal platform for the evaluation of drug sensitivities, accurately reflecting the patient's therapeutic response to the drugs.
详细描述
This study aims to test the feasibility of Quadratic Phenotypic Optimization Platform (QPOP) application in high grade astrocytic glioma, by first establishing clinically relevant high grade astrocytic glioma organoid models, followed by the utility of QPOP-derived drug combinations in high grade astrocytic glioma.
The primary purpose of this study is not hypothesis testing, but to assess the feasibility of QPOP-guided therapy for recurrent high grade astrocytic glioma to be used in a larger scale study. Therefore, this study does not have a formal sample size, but rather, a set benchmarks to determine feasibility.
Specific Aim 1: To establish primary and corresponding temozolomide/radiotherapy (TMZ/RT)-resistant high grade astrocytic glioma patient-derived organoids.
Specific Aim 2: To determine the utility of QPOP (Quadratic Phenotypic Optimization Platform)-derived drug combinations in treating recurrent high grade astrocytic glioma.
Specific Aim 3: To evaluate the use of non-invasive imaging tools (Ga68-NEB PET/MRI and DCE-MRI) to track BBB permeability over time in high grade astrocytic glioma patients, and correlate this with pathological biomarkers, therapeutic response determined by follow up standard MRI and clinical outcomes.
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
- 21 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pre-screening:
- •Patients 21 years of age or older, with ECOG performance status 0 to 2, and with a life expectancy of more than 3 months with suspected high grade astrocytic glioma, fit for treatment comprising standard-of-care therapy with adjuvant temozolomide and radiotherapy if the diagnosis of high grade astrocytoma is pathologically confirmed.
- •Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent.
- •Patients will be enrolled at the time of initial surgery but study imaging and further PDO generation will not take place if the patient is subsequently found not to meet the histological criteria or will not be receiving standard adjuvant temozolomide/ radiotherapy.
- •All subsequent criteria apply to the main study only:
- •Patients 21 years of age or older, with ECOG performance status 0 to 2, and life expectancy of more than 3 months with pathologically confirmed high grade astrocytic glioma, having undergone first-line standard-of-care therapy with surgery/biopsy followed by temozolomide and radiotherapy. Subjects with truncated adjuvant chemoradiotherapy may be enrolled at the Principal Investigator's discretion.
- •Documented tumor progression based on standard clinical, radiological or histological criteria, and deemed suitable for second line systemic therapy.
- •Sufficient tumor tissue available for PDO generation at baseline and at least one available or pending QPOP result.
- •Adequate organ function as defined by:
- •1. Bone marrow function i. Haemoglobin ≥ 9g/dl ii. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L iii. Platelet count ≥ 100 x 109/L.
- •Liver function i. Bilirubin < 2.5x upper limit of normal (ULN) ii. Alanine transaminase (ALT) and aspartate transaminase (AST) < 2.5x ULN or < 5x ULN if liver metastases are present iii. Prothrombin time (PT) within the normal range for the institution.
- •Renal function i. Plasma creatinine <1.5x institutional ULN 5) Capable of swallowing tablets. 6) Recovery from any previous drug- or procedure-related toxicity to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 Grade 0 or 1 (except alopecia), or to baseline preceding the prior treatment.
- •Exclusion Criteria (both pre-screening/ main study)
- •Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 2 weeks of study entry.
- •Pregnancy or breastfeeding at the point where systemic anti-cancer therapy is initiated. Women of childbearing potential must have a negative pregnancy test at the point where systemic anti-cancer therapy is initiated. Women of childbearing potential and men, must agree to use adequate contraception (barrier method of birth control) while on anti-cancer treatment and until at least 3 months after the last study drug administration.
- •Concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours (Ta, Tis & T1) or any cancer curatively treated less than 5 years prior to study entry.
- •Patients with leptomeningeal dissemination of disease and/or pure spinal high grade gliomas will be excluded.
- •Kidney disease which would clinically disqualify the subject from serial MRI scans with gadolinium contrast.
排除标准
- 未提供
研究组 & 干预措施
QPOP-guided chemotherapy
Subjects enrolled in the study will be administered combination of chemotherapy derived from QPOP analysis based on in vitro drug screening panels which comprises anti-cancer agents which have previously been evaluated in recurrent high grade astrocytic glioma.
干预措施: QPOP category 1 (Drug)
QPOP-guided chemotherapy
Subjects enrolled in the study will be administered combination of chemotherapy derived from QPOP analysis based on in vitro drug screening panels which comprises anti-cancer agents which have previously been evaluated in recurrent high grade astrocytic glioma.
干预措施: QPOP category 2 (Drug)
结局指标
主要结局
Six-month progression-free survival (PFS 6)
时间窗: up to 6 months
Defined as the time from the start of study treatment to documented progression of disease or death; PFS6 refers to the percentage of patients who are alive and free of high grade astrocytic glioma progression at 6 months.
次要结局
- Twelve-month overall survival (OS12)(Up to 12 months)
- Radiological response at follow up MRI(Up to 6 months)
- Number of participant with treatment related haematological and non-haematological toxicities(Up to 6 months)