Pharmacokinetic boosting of olaparib: Study protocol of a multicentre, open-label, randomised, non-inferiority trial (PROACTIVE-B)

IF 1.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary Clinical Trials Communications Pub Date : 2025-03-29 DOI:10.1016/j.conctc.2025.101477

Joanneke K. Overbeek , Niels A.D. Guchelaar , Ma Ida Mohmaed Ali , Muriëlle Sark , Carolien Hovenier , Wietske Kievit , Marjolijn J.L. Ligtenberg , Petronella B. Ottevanger , Haiko J. Bloemendal , Stijn L.W. Koolen , Ron H.J. Mathijssen , Ingrid A. Boere , Alwin D.R. Huitema , Gabe S. Sonke , Frans L. Opdam , Rob ter Heine , Nielka P. van Erp

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引用次数: 0

Abstract

Background

Pharmacokinetic (PK) boosting is the intentional use of a drug-drug interaction to enhance systemic drug exposure. PK boosting of the anticancer drug olaparib, a CYP3A-substrate, has the potential to reduce PK variability, side effects and financial burden associated with this drug. After establishing adequate pharmacokinetic exposure with boosting in the PROACTIVE-A study, the PROACTIVE-B study is designed to evaluate non-inferiority for both efficacy and toxicity of the boosted therapy compared to the standard monotherapy of olaparib.

Methods

The PROACTIVE-B study is a nationwide, multicentre, prospective, randomized, non-inferiority trial. A total of 142 patients (128 patients with BRCA+, high-grade, FIGO III/IV ovarian cancer who receive olaparib as maintenance therapy; 14 patients with other approved indications for olaparib) who start olaparib treatment in line with the drug label will be randomized between the standard monotherapy of olaparib 300 mg twice daily (BID) and the boosted therapy of olaparib 100 mg BID with cobicistat 150 mg BID. The co-primary objectives are tolerability (dose reductions due to toxicity), and efficacy (progression-free survival at 12 months) in the ovarian cancer population. Secondary objectives include health status (EQ-5D-5L), patient satisfaction (Cancer Therapy Satisfaction Questionnaire (CTSQ)), and cost effectiveness using the institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ) and iMTA Medical Consumption Questionnaire (iMCQ).

Discussion

PK boosting of olaparib is a potentially valuable strategy to reduce the olaparib dose and the variability in olaparib exposure with fewer side effects. Moreover, the lower costs related to the boosted therapy contribute to a durable and accessible anticancer treatment for all patients.

Trial registration

The PROACTIVE study has been published at ClinicalTrials.gov under NCT05078671 on October 14, 2021 and at EudraCT under 2021-004032-28 on August 24, 2021.

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奥拉帕尼的药代动力学增强：一项多中心、开放标签、随机、非劣效性试验（PROACTIVE-B）的研究方案

药代动力学（PK）增强是有意利用药物-药物相互作用来增强全身药物暴露。抗肿瘤药物奥拉帕尼（olaparib）是一种cyp3a底物，它的PK增强有可能减少与该药物相关的PK变异性、副作用和经济负担。在PROACTIVE-A研究中建立了充分的药代动力学暴露后，PROACTIVE-B研究旨在评估与奥拉帕尼标准单药治疗相比，增强疗法的疗效和毒性的非劣效性。方法PROACTIVE-B研究是一项全国性、多中心、前瞻性、随机、非劣效性试验。共有142例患者(128例BRCA+、高级别、FIGO III/IV型卵巢癌患者接受奥拉帕尼作为维持治疗；14名有其他经批准的奥拉帕尼适应症的患者根据药物标签开始奥拉帕尼治疗，将被随机分配到奥拉帕尼300 mg每日两次（BID）的标准单药治疗和奥拉帕尼100 mg BID加cobicistat 150 mg BID的强化治疗之间。共同的主要目标是卵巢癌人群的耐受性（由于毒性引起的剂量减少）和有效性（12个月无进展生存期）。次要目标包括健康状况（EQ-5D-5L），患者满意度（癌症治疗满意度问卷（CTSQ）），以及使用医疗技术评估研究所（iMTA）生产力成本问卷（iPCQ）和iMTA医疗消费问卷（iMCQ）的成本效益。奥拉帕尼的pk增强是一种潜在的有价值的策略，可以减少奥拉帕尼剂量和奥拉帕尼暴露的变异性，同时减少副作用。此外，与增强疗法相关的较低成本有助于为所有患者提供持久和可获得的抗癌治疗。该前瞻性研究已于2021年10月14日在ClinicalTrials.gov上发布，编号为NCT05078671，并于2021年8月24日在EudraCT上发布，编号为2021-004032-28。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Contemporary Clinical Trials Communications Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

2.70

自引率

6.70%

发文量

146

审稿时长

20 weeks

期刊介绍： Contemporary Clinical Trials Communications is an international peer reviewed open access journal that publishes articles pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from a wide range of disciplines including medicine, life science, pharmaceutical science, biostatistics, epidemiology, computer science, management science, behavioral science, and bioethics. Contemporary Clinical Trials Communications is unique in that it is outside the confines of disease specifications, and it strives to increase the transparency of medical research and reduce publication bias by publishing scientifically valid original research findings irrespective of their perceived importance, significance or impact. Both randomized and non-randomized trials are within the scope of the Journal. Some common topics include trial design rationale and methods, operational methodologies and challenges, and positive and negative trial results. In addition to original research, the Journal also welcomes other types of communications including, but are not limited to, methodology reviews, perspectives and discussions. Through timely dissemination of advances in clinical trials, the goal of Contemporary Clinical Trials Communications is to serve as a platform to enhance the communication and collaboration within the global clinical trials community that ultimately advances this field of research for the benefit of patients.