A Randomized, Double-Blind, Placebo-Controlled Phase III Study of First-Line Maintenance Tarceva Versus Tarceva at the Time of Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following 4 Cycles of Platinum-Based Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 643
- 主要终点
- Percentage of Participants Who Died During the Overall Study
研究概览
简要总结
This double-blind, placebo-controlled study will evaluate the benefit of first-line maintenance erlotinib (Tarceva) versus erlotinib at the time of disease progression in participants with advanced NSCLC who have not progressed following 4 cycles of platinum based-chemotherapy and whose tumor does not harbor an epidermal growth factor receptor (EGFR)-activating mutation. Participants will be randomized to receive either erlotinib 150 milligrams (mg) orally (PO) once daily or placebo. Participants who progress on placebo will receive erlotinib 150 mg PO once daily as second-line therapy, and those who progress on erlotinib may switch to a non-investigational, second-line chemotherapy. Treatments will continue until disease progression, death, or unacceptable toxicity. Participants may also be entered into a final Survival Follow-Up (SFU) period upon treatment discontinuation.
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
- Double (Participant, Investigator)
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
- •Adults greater than or equal to (≥) 18 years of age, or legal age of consent if greater than 18
- •Advanced or recurrent (Stage IIIB) or metastatic (Stage IV) NSCLC
- •Completion of 4 cycles of platinum-based chemotherapy without progression (end of last chemotherapy cycle less than or equal to [≤] 28 days prior to randomization)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
排除标准
- •Prior exposure to agents directed at human epidermal growth factor receptor (HER) axis (e.g. erlotinib, gefitinib, cetuximab)
- •Participants whose tumors harbor an EGFR-activating mutation
- •Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease before Screening
- •Use of pemetrexed in maintenance setting (pemetrexed allowed during the chemotherapy run-in)
- •Participants who have undergone complete tumor resection after responding to the platinum-based chemotherapy during the Screening phase
- •Any other malignancies within 5 years, except for curatively resected carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ, or organ-confined prostate cancer
- •Central nervous system (CNS) metastases or spinal cord compression that has not been definitely treated with surgery and/or radiation, or treated CNS metastases or spinal cord compression without stable disease for ≥2 months
- •Human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
- •Any inflammatory changes of the surface of the eye
研究组 & 干预措施
Early Erlotinib
Participants will receive blinded erlotinib as 150 mg PO once daily in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrate disease progression may be unblinded to receive an approved second-line therapy (but not EGFR targeted therapies) until disease progression, death, or unacceptable toxicity. Participants may be observed during a final SFU period after discontinuation from study treatment.
干预措施: Erlotinib (Drug)
Early Erlotinib
Participants will receive blinded erlotinib as 150 mg PO once daily in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrate disease progression may be unblinded to receive an approved second-line therapy (but not EGFR targeted therapies) until disease progression, death, or unacceptable toxicity. Participants may be observed during a final SFU period after discontinuation from study treatment.
干预措施: Second-Line Chemotherapy (Drug)
Late Erlotinib
Participants will receive blinded placebo tablets PO once daily in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrate disease progression may be unblinded to receive second-line erlotinib as 150 mg PO once daily until disease progression, death, or unacceptable toxicity. Participants may be observed during a final SFU period after discontinuation from study treatment.
干预措施: Placebo (Drug)
Late Erlotinib
Participants will receive blinded placebo tablets PO once daily in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrate disease progression may be unblinded to receive second-line erlotinib as 150 mg PO once daily until disease progression, death, or unacceptable toxicity. Participants may be observed during a final SFU period after discontinuation from study treatment.
干预措施: Erlotinib (Drug)
结局指标
主要结局
Percentage of Participants Who Died During the Overall Study
时间窗: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death)
Participants were followed for survival until death or premature withdrawal. The percentage of participants who died during the Overall Study (BP, OLP, or SFU) was calculated.
Percentage of Participants Event-Free (Alive) at 1 Year During the Overall Study
时间窗: At 1 year
Participants were followed for survival until death or premature withdrawal. The percentage of participants event-free (i.e., still alive) at 1 year during the Overall Study was calculated.
Overall Survival (OS) as Median Time to Event During the Overall Study
时间窗: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death)
Participants were followed for survival until death or premature withdrawal. OS was defined as the interval between date of randomization and date of death from any cause. Median time to event during the Overall Study (BP, OLP, or SFU) was estimated using the Kaplan-Meier method and expressed in months.
次要结局
- Progression-Free Survival (PFS) as Median Time to Event During Blinded Treatment(Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP))
- Percentage of Participants Who Died or Experienced Disease Progression During Blinded Treatment(Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP))
- Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to RECIST During Blinded Treatment(Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP))
- Percentage of Participants Event-Free (Alive and No Disease Progression) at 6 Months During Blinded Treatment(At 6 months)
- Percentage of Participants With CR, PR, or SD According to RECIST During Blinded Treatment(Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP))
- Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment(Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP))