Modified osimertinib dosing, with or without cobicistat as a pharmacokinetic booster, to improve cost-effectiveness of advanced Non-Small Cell Lung Cancer treatment - OSIBOOST 2
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 5
- 主要终点
- OSIBOOST 2-A: The daily cumulative dose reduction accomplished in individual patients, while retaining osimertinib exposure (i.e. osimertinib trough (Cmin,SS) levels within the specified provisional therapeutic range (125 – 259 ng/mL).
研究概览
简要总结
This study will consist of two sub-studies in patients with advanced EGFR mutated NSCLC. Depending on disease status, patients may be enrolled in sub-study A (stable disease or better) or B (CNS oligoprogression):
OSIBOOST 2-A: is a single-arm near-equivalence study, intended to assess the clinical feasibility of a modified osimertinib dosing strategy combining therapeutic drug monitoring, osimertinib dose-modification and pharmacokinetic (PK) boosting, in order to improve osimertinib cost-effectiveness and reduce toxicity while maintaining clinical efficacy. This study will include patients with advanced EGFR positive NSCLC who are treated with osimertinib as part of regular care. The primary objective is to evaluate the clinical feasibility of a modified osimertinib dosing strategy to allow for a personalized, more cost-effective osimertinib dosing schedule while maintaining osimertinib exposure within the provisional, clinically-proven, therapeutic window (125 – 259 ng/mL).
OSIBOOST 2-B: is an exploratory single-arm pharmacokinetic boosting study, designed to assess whether PK boosting provides a viable therapeutic option in patients with asymptomatic central nervous system (CNS) oligoprogression. The primary objective is to assess whether boosting standard (unaltered) osimertinib treatment can result in renewed CNS disease control, as a cost-effective alternative for off-label, non-reimbursable, dose-escalation to 160 mg osimertinib once daily (QD).
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •The patient receives osimertinib 80 mg once daily as part of their standard treatment plan.
- •The patient has a World Health Organisation (WHO) Performance Status (PS) of 0-
- •The patient is 18 years or older.
- •The patient is able and willing to sign informed consent.
- •The patient is able and willing to undergo additional blood sampling (e.g. for therapeutic drug monitoring).
- •The patient consents to their blood being analysed for CYP3A-genotype.
- •OSIBOOST 2-A: the patient has non-squamous advanced EGFR-mutated NSCLC with no signs of imminent progression (CT-confirmed). If the patient does have signs of progression, they are only eligible if their treating physician deems treatment beyond progression to be appropriate.
- •OSIBOOST 2-B: the patient has non-squamous EGFR-mutated NSCLC with radiologically confirmed (RANO-progressive) asymptomatic intracranial progression, not in an eloquent area. Furthermore, extracranial disease should be controlled (no RECIST v1.1 progression).
排除标准
- •The patient is taking any other drug or herbal substance which 1) is known to strongly inhibit CYP3A, P-gp or BCRP activity; 2) is primarily metabolized by CYP3A, P-gp or BCRP and has a small therapeutic range; or 3) may otherwise affect CYP3A, P-gp or BCRP metabolic activity.
- •The patient has impaired gastrointestinal function that may alter the absorption of osimertinib or cobicistat (e.g. ulcerative disease, uncontrolled nausea or vomiting, malabsorption syndrome, small bowel resection).
- •The patient has chronic liver disease (Child-Pugh score: class C).
- •The patient is either pregnant or breastfeeding.
结局指标
主要结局
OSIBOOST 2-A: The daily cumulative dose reduction accomplished in individual patients, while retaining osimertinib exposure (i.e. osimertinib trough (Cmin,SS) levels within the specified provisional therapeutic range (125 – 259 ng/mL).
OSIBOOST 2-A: The daily cumulative dose reduction accomplished in individual patients, while retaining osimertinib exposure (i.e. osimertinib trough (Cmin,SS) levels within the specified provisional therapeutic range (125 – 259 ng/mL).
OSIBOOST 2-B: CNS disease control rate (DCR) at 12 weeks.
OSIBOOST 2-B: CNS disease control rate (DCR) at 12 weeks.
次要结局
- Osimertinib and AZ5104 trough concentrations in plasma during steady state
- Number of (Serious) Adverse Events and Suspected Unexpected Serious Adverse Reaction events during trial course and follow-up.
- OSIBOOST 2-A: Average osimertinib intake reduction over time.
- Progression-Free Survival (PFS) during osimertinib/cobicistat concomitant treatment.
- CYP3A genotype.
- OSIBOOST 2-B: Trough concentrations levels at steady state for osimertinib and AZ5104 in cerebrospinal fluid.
- OSIBOOST 2-B: ctDNA analysis of cerebrospinal fluid.
研究者
Sander Croes
Scientific
University Hospital Maastricht