Double-Blind Randomized Phase II Trial of Carboplatin and Pemetrexed With or Without OGX-427 in Patients With Previously Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer (The Spruce Clinical Trial)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 155
- 试验地点
- 16
- 主要终点
- Median Progression-Free Survival
研究概览
简要总结
This randomized phase II study will compare the efficacy and safety of the combination of carboplatin and pemetrexed with and without OGX-427 in patients with previously untreated advanced non-squamous NSCLC.
详细描述
Modern doublet chemotherapy improves survival in patients with advanced non-small cell lung cancer (NSCLC) compared with supportive care alone, with non-squamous NSCLC patients treated with platinum/pemetrexed living longer than patients treated with platinum/gemcitabine. Despite these advances, poor outcomes with advanced disease warrant exploration of novel drugs with unique mechanisms of action. Preclinical evidence in lung cancer models shows promising antitumor activity with OGX-427 in combination with platinum based therapy or pemetrexed. In this double-blind, placebo-controlled, Phase II study, pemetrexed and carboplatin plus OGX-427 followed by maintenance pemetrexed and OGX-427 will be compared with pemetrexed and carboplatin plus placebo followed by maintenance pemetrexed and placebo in patients with previously untreated advanced non-squamous NSCLC.
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)
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
- •Histologic or cytologic diagnosis of advanced NSCLC, excluding squamous cell and small cell histology. Tumors with mixed NSCLC histologies are eligible, as long as the predominant histology is not squamous. If small-cell elements are present or not otherwise specified histologically, the patient is not eligible.
- •Metastatic disease (according to American Joint Committee on Cancer (AJCC) staging system, v7.0).
- •No prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy for metastatic disease; previous adjuvant or neoadjuvant therapy for Stage I, II, or III disease is allowed as long as the interval from the end of treatment until disease progression was >12 months.
- •No prior radiation therapy to the whole pelvis or to ≥25% of the total bone marrow area. Other radiation therapy must be completed at least 2 weeks prior to study entry. Must have recovered from acute adverse effects prior to study entry.
- •At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or
- •Baseline laboratory values as follows:
- •Absolute neutrophil count (ANC) ≥1500/μL
- •Hemoglobin (Hgb) ≥10 g/dL
- •Platelets ≥100,000/μL
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ≤3.0 x the upper limit of normal (ULN); 5 x ULN if known hepatic metastases.
- •Total bilirubin ≤1.5 x ULN, unless secondary to Gilbert's disease
- •Serum creatinine ≤1.5 x ULN. If creatinine is >1.5, calculate creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method:
- •Glomerular Filtration Rate (GFR) = (140-age) x (weight/kg) x (0.85 if female)/(72 x serum creatinine mg/dL)
- •Fertile male patients willing to use adequate contraceptive measures.
- •Female patients who are not of child-bearing potential, and fertile female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of randomization.
- •Life expectancy ≥ 12 weeks.
- •Must be ≥18 years of age at the time of consent.
- •Willingness and ability to comply with trial and follow-up procedures.
- •Ability to understand the nature of this trial and give written informed consent.
排除标准
- •Known anaplastic lymphoma kinase (ALK) translocation and epidermal growth factor receptor (EGFR) "activating" mutations where first-line treatment with targeted tyrosine kinase inhibitor therapy is more appropriate.
- •Known central nervous system (CNS) disease other than neurologically stable, treated brain metastases defined as metastasis having no evidence of progression or hemorrhage after treatment and no ongoing requirements for corticosteroids, (e.g., dexamethasone) for at least 2 weeks.
- •Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:
- •Unstable angina pectoris
- •Congestive heart failure
- •Acute myocardial infarction
- •Conduction abnormality not controlled with pacemaker or medication
- •Significant ventricular or supraventricular arrhythmias (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
- •Patients currently receiving therapeutic anticoagulation.
- •Pregnant or lactating women.
- •Any serious, active underlying medical condition that would impair the ability of the patient to receive study treatment, such as diabetes mellitus or infection.
- •Unable or unwilling to take folic acid or vitamin B
- •Active second malignancy (except non-melanomatous skin or superficial bladder cancer) defined as requiring current need for cancer therapy or at high risk of recurrence (>30%) during the study.
- •Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- •Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.
研究组 & 干预措施
OGX-427
Three loading doses of OGX-427 at 600mg intravenously (IV) will be administered over 9 days. Following the loading dose period, OGX-427 will be administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle during the Treatment Phase. The Treatment Phase will be followed by a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle.
干预措施: OGX-427 (Drug)
Placebo
Three loading doses of placebo will be administered intravenously (IV) over 9 days. Following the loading dose period, placebo will be administered IV weekly Days 1, 8 and 15 of each 21 day cycle during the Treatment Phase. The Treatment Phase will be followed by a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle.
干预措施: Placebo (Drug)
结局指标
主要结局
Median Progression-Free Survival
时间窗: Every 6 weeks for up to 24 months
Defined as the time (in months) from date of randomization to the date of first observation of progression based on radiological assessment by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, or date of death from any cause, in the absence of progressive disease (PD) or censored at the date of last adequate tumor assessment. Progressive Disease is defined by RECIST v1.1 as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest (nadir) sum while on study (this includes the baseline sum if that is the smallest on study), or the appearance of one or more new lesions.
次要结局
- Number of OGX-427 Versus Placebo Participants With an Objective Response(Every 6 weeks for up to 24 months)
- Median Overall Survival(Every 6 weeks for up to 41 months)
- Number of Patients With a Treatment-Related Adverse Event as a Measure of Safety.(Weekly during each 21 days cycle and for 30 days after last dose for up to 29 Months)