A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Pemetrexed Chemotherapy Plus Osimertinib Versus Platinum Plus Pemetrexed Chemotherapy Plus Placebo in Patients With EGFRm, Locally Advanced or Metastatic NSCLC Who Have Progressed Extracranially Following First-Line Osimertinib Therapy (COMPEL)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 98
- 试验地点
- 40
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The study will evaluate the efficacy and safety of treatment with chemotherapy in combination with osimertinib compared to chemotherapy in combination with placebo in patients whose disease has progressed extracranially following first-line osimertinib treatment.
详细描述
This is a Phase III, randomized, double-blind, placebo-controlled study of platinum plus pemetrexed chemotherapy plus osimertinib versus platinum plus pemetrexed chemotherapy plus placebo in patients with epidermal growth factor receptor mutation-positive (EGFRm), locally advanced or metastatic NSCLC with or wihout stable brain metastases who responded to first-line osimertinib therapy (complete response [CR] or partial response [PR]) or stable disease (SD) for ≥ 6 months during first-line osimertinib treatment, and subsequently experienced radiological, extracranial disease progression. Approximately 204 patients were to be randomized in a 1:1 ratio to treatment with platinum plus pemetrexed chemotherapy plus osimertinib (Treatment Arm A) or platinum plus pemetrexed chemotherapy plus placebo (Treatment Arm B). However, the number of patients has been reduced to approximately 80 patients due to treatment landscape changes which outpaced study recruitment. Patients will be stratified based on the presence of brain metastases (stable brain metastases based on central nervous system (CNS) Response Evaluation Criteria in Solid Tumors, Version 1.1 [RECIST 1.1] assessments versus no brain metastases).
The 2 randomized treatment regimens are as follows:
- Treatment Arm A: Osimertinib 80 mg once daily (QD) with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin (area under the concentration-time curve [AUC] 5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by osimertinib 80 mg QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles
- Treatment Arm B: Placebo QD with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin (AUC5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by placebo QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The patient, the Investigator, the study team (Sponsor, Contract research organization) and the study site staff will be blinded to osimertinib or placebo allocation. Patients may participate in the open label part of trial at the discretion of the investigator to receive osimertinib and continue any ongoing chemotherapy if intracranial progression is their first progression event.
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
- •Pathologically confirmed non-squamous NSCLC.
- •Locally advanced (clinical stage IIIB or IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC, not amenable to curative surgery or radiotherapy.
- •Evidence of radiological extracranial disease progression following (Investigator-assessed) response or SD for ≥ 6 months during first-line osimertinib treatment, but who have not received further, subsequent treatment.
- •Tumor known to harbor 1 of the 2 or both common epidermal growth factor receptor (EGFR) mutations known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M.
- •World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.
- •Life expectancy >12 weeks at Day
- •At least 1 lesion, not previously irradiated, that can be accurately measured.
- •Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling criteria at screening.
- •Male patients must be willing to use barrier contraception
排除标准
- •Clinical or radiological evidence of CNS progression on first-line osimertinib.
- •Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD/pneumonitis.
- •Any evidence of severe or uncontrolled systemic diseases.
- •Any of the following cardiac criteria:
- •i) Mean resting QTc >470 msec ii) Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram iii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
- •Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of investigational product (IP).
- •Any unresolved toxicities from prior therapy.
- •Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib.
- •More than 4 weeks elapsed since last dose of osimertinib by date of randomization.
- •Unable to tolerate osimertinib 80 mg first-line therapy.
- •Prior treatment with any systemic anti-cancer therapy.
- •Major surgery within 4 weeks of the first dose of IP.
- •Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP.
- •Current use of medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A
- •Participation in another clinical study with an IP other than first-line osimertinib during the 4 weeks prior to Day 1.
研究组 & 干预措施
Treatment Arm A
All randomized patients will receive osimertinib 80 mg QD with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin ([AUC] 5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by osimertinib 80 mg QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles
干预措施: Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin (Drug)
Treatment Arm B
All randomized patients will receive placebo QD with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin (AUC5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by placebo QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles
干预措施: Placebo for osimertinib (AZD9291) pemetrexed cisplatin or carboplatin (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From date of first dose (Day 1) until date of progression at local site or death due to any cause or data cut-off date whichever occurred first (up to 3 years 1 month)
Progression free survival is defined as time from randomization until progression (intracranial or extracranial, whichever occurs first) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for extracranial progression) and Central nervous system (CNS) RECIST 1.1 (for intracranial progression) as assessed by the Investigator at local site or death due to any cause.
次要结局
- Intracranial Progression Free Survival in Participants With Brain Metastases at Baseline(Assessed from date of first dose (Day 1) until date of intracranial progression at local site or death due to any cause or data cut off date whichever occurred first (up to 3 years 1 month), data for 6 months reported)
- Intracranial Progression Free Survival in Participants Without Brain Metastases at Baseline(Assessed from date of first dose (Day 1) until date of intracranial progression at local site or death due to any cause or data cut off date whichever occurred first (up to 3 years 1 month), data for 6 months reported)
- Intracranial Progression Free Survival With Brain Metastases at Baseline(Assessed from date of first dose (Day 1) until date of intracranial progression at local site or death due to any cause or data cut off date whichever occurred first (up to 3 years 1 month), data for 6 months reported)
- Intracranial Progression Free Survival Without Brain Metastases at Baseline(Assessed from date of first dose (Day 1) until date of intracranial progression at local site or death due to any cause or data cut off date whichever occurred first (up to 3 years 1 month), data for 6 months reported)
- Extracranial Progression Free-survival(From date of first dose (Day 1) until date of extracranial progression at local site or death due to any cause or data cut-off date whichever occurred first (up to 3 years 1 month))
- Overall Survival (OS)(From date of first dose (Day 1) until post progression survival follow-up (up to 3 years 1 month))