A Phase III, Multicenter, Randomized, Double Blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Canakinumab Versus Placebo as Adjuvant Therapy in Adult Subjects With Stages AJCC/UICC v. 8 II -IIIA and IIIB (T>5cm N2) Completely Resected (R0) Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1,382
- 试验地点
- 21
- 主要终点
- Disease Free Survival (DFS) by Local Investigator
研究概览
简要总结
The primary purpose of the study was to compare the efficacy and safety of canakinumab versus placebo as adjuvant therapy in adult subjects with stages II -IIIA according to the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) and the subset of IIIB (T>5cm N2 disease) completely resected (R0) non-small cell lung cancer (NSCLC).
详细描述
This was a phase III, multicenter, randomized, double-blind study to evaluate the efficacy and safety of canakinumab as adjuvant therapy in adult patients with stages AJCC/UICC v.8 II-IIIA and IIIB (T>5 cm N2) completely resected (R0) NSCLC.
Approximately 1500 patients were planned to be randomized 1:1 to canakinumab, 200 mg subcutaneously (s.c.) every 3 weeks or matching placebo s.c. every 3 weeks. Patients were planned to continue their assigned treatment until they completed 18 cycles (cycle= 21 days) or experienced any one of the following: non-small cell lung cancer (NSCLC) disease recurrence as determined by Investigator; unacceptable toxicity that precluded further treatment; treatment discontinuation at the discretion of the Investigator or patient; start of a new antineoplastic therapy; death, or loss to follow-up, whichever occurred first. All patients who discontinued from the study treatment were to be followed up every 12 weeks for survival until the final OS analysis or death, loss to follow-up or withdrawal of consent for survival follow-up.
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
- •Had completely resected (R0) NSCLC AJCC/UICC v. 8 stage IIA-IIIA and IIIB (N2 disease only) OR had NSCLC Stage IIA-IIIA, IIIB (N2 disease only) and were candidates for complete resection surgery.
- •Cisplatin-based chemotherapy was mandatory for all subjects (Exception: In subjects with stage IIA disease with no nodal involvement, cisplatin-based chemotherapy could be administered if recommended by the treating physician). When required, a minimum of two cycles of cisplatin-based chemotherapy was mandatory, after which additional therapies could be given based upon local clinical practice and/or guidelines. Typically, chemotherapy was initiated within 60 days of surgery.
- •Radiation therapy was allowed if indicated as per local guidelines or practice.
- •Had recovered from all toxicities related to prior systemic therapy to grade ≤ 1 (CTCAE v 5.0). Exception to this criterion: subjects with any grade of alopecia and grade 2 or less neuropathy were allowed to enter the study
- •Had ECOG performance status (PS) of 0 or 1
排除标准
- •Had unresectable or metastatic disease, positive microscopic margins on the pathology report, and/or gross disease remaining at the time of surgery
- •Had received any neoadjuvant therapy
- •Had presence or history of a malignant disease, other than the resected NSCLC, that had been diagnosed and/or required therapy within the past 3 years Exceptions to this exclusion included the following: completely resected basal cell and squamous cell skin cancers, completely resected carcinoma in situ of any type and hormonal maintenance for breast and prostate cancer > 3 years.
- •Had a history of current diagnosis of cardiac disease
- •Had uncontrolled diabetes
- •Had known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (positive or indeterminate central laboratory results)
- •Subjects had to be evaluated for tuberculosis as per local treatment guidelines or clinical practice. Subjects with active tuberculosis were not eligible.
- •Had suspected or proven immunocompromised state as described in the protocol
- •Had live and attenuated vaccination within 3 months prior to first dose of study drug (e.g. MMR, Yellow Fever, Rotavirus, Smallpox, etc.).
研究组 & 干预措施
canakinumab
Participants received 200mg of canakinumab subcutaneously every 3 weeks for up to 18 cycles (approximately 54 weeks)
干预措施: Canakinumab (Drug)
Placebo
Participants received canakinumab placebo subcutaneously every 3 weeks for up to 18 cycles (approximately 54 weeks)
干预措施: Placebo (Drug)
结局指标
主要结局
Disease Free Survival (DFS) by Local Investigator
时间窗: Up to approximately 4 years
DFS is the time from the date of randomization to the date of the first documented NSCLC disease recurrence as assessed by local investigator radiologically or death due to any cause. Disease recurrence included diagnoses of new primary lung malignancies. Clinical deterioration was not considered as a recurrence of disease. In case of non-conclusive radiological evidence, a biopsy assessment was performed to confirm NSCLC recurrence. The median DFS was estimated using the Kaplan-Meier method. DFS was censored if no DFS event was observed prior to the analysis cut-off date or subjects who received any subsequent anti-neoplastic therapy for NSCLC. The censoring date was the date of last assessment before the cut-off date or NSCLC related anti-neoplastic therapy date.
次要结局
- Disease Free Survival (DFS) by Local Investigator in PD-L1 Subgroups(Up to approximately 4 years)
- Lung Cancer Specific Survival (LCSS)(Up to approximately 4.3 years)
- Canakinumab Serum Concentrations(Cycle 1 on day 1 (pre-dose), day 8 and 15; Cycle 2, 4, 6, 9 and 12 on day 1 (pre-dose). Cycle=21 days)
- Time to Definitive 10 Point Deterioration Symptom Scores of Pain,Cough and Dyspnea Per European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ)- Lung Cancer (LC) 13 Questionnaire(From baseline up to approximately 4 years)
- Overall Survival (OS) in PD-L1 Subgroups(Up to approximately 4.3 years)
- Disease Free Survival (DFS) by Local Investigator in CD8 Subgroups(Up to approximately 4 years)
- Canakinumab Anti-drug Antibody (ADA) Prevalence at Baseline(Baseline)
- Change From Baseline in the Utility Score of the EuroQoL- 5 Dimension- 5 Level (EQ-5D-5L)(Baseline, every 3 weeks for 14 months; end of treatment; every 4 weeks up to 130 days post-treatment; at 18,24,30,36 and 48 months post-randomization (if no recurrence); 7 and 28 days post-disease progression, up to approx. 4 years.)
- Overall Survival (OS)(Up to approximately 4.3 years)
- Overall Survival (OS) in CD8 Subgroups(up to approximately 4.3 years)
- Canakinumab ADA Incidence(From baseline up to 130 days after end of treatment, assessed up to approx. 1.5 years)
- Time to First 10 Point Deterioration for Symptom Scores of Pain, Cough and Dyspnea Per EORTC QLQ-LC13 Questionnaire(From baseline up to approximately 4 years)
- Time to Definitive 10 Point Deterioration of Global Health Status/Quality of Life (QoL), Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire(From baseline up to approximately 4 years)
- Time to First 10 Point Deterioration of Global Health Status/QoL, Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire(From baseline up to approximately 4 years)