A Randomized, Multicenter, Open-Label Phase 3 Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Gemcitabine-Cisplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,093
- 试验地点
- 2
- 主要终点
- Overall Survival Time (OS)
研究概览
简要总结
The research study is testing the investigational drug necitumumab (IMC-11F8) in the treatment of advanced non-small cell lung cancer. The aim of this study is to determine if necitumumab, given together with a standard chemotherapy combination consisting of cisplatin and gemcitabine will be more effective in improving participant disease than the standard chemotherapy combination alone.
详细描述
Multinational, randomized, multicenter, open-label, Phase III study of 1093 participants (age ≥ 18 years) with histologically- or cytologically-confirmed, stage IV squamous-cell NSCLC, who have received no prior therapy for metastatic disease, will be randomized on a 1:1 basis to receive first-line necitumumab plus chemotherapy consisting of gemcitabine and cisplatin in study Arm A, or gemcitabine-cisplatin chemotherapy alone in study Arm B. Baseline radiographic assessment of disease will be performed within 21 days prior to randomization (first treatment will be administered within 7 days following randomization). Participants will undergo radiographic assessment of disease status (computed tomography or magnetic resonance imaging) every 6 weeks (± 3 days), until there is radiographic documentation of progressive disease (PD). Chemotherapy will continue for a maximum of six cycles in each arm (or until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance or withdrawal of consent); participants in Arm A only will continue to receive necitumumab until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.
After the end-of-study-visit (following PD), follow-up information regarding further anticancer treatment and survival will be collected every 2 months (± 7 days). For participants who discontinue study for reasons other than PD (eg, symptomatic deterioration), information on disease progression will also be collected until PD is documented. Follow-up will continue as long as the participant is alive, or until the end of the trial.
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
- None
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
- •Has histologically or cytologically confirmed squamous NSCLC
- •Has Stage IV disease at the time of study entry
- •Measurable or nonmeasurable disease at the time of study entry as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) (participants with only truly nonmeasurable disease are not eligible)
- •Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)
- •Has adequate hepatic function
- •Has adequate renal function
- •Has adequate hematologic function
- •If female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method (failure rate < 1%) during and for 6 months after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method)
- •If male, the participant is surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
- •Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization
- •Has archived tumor tissue available for analysis of EGFR and KRAS mutation status (by PCR) and EGFR gene copy number (by FISH); minimum of four slides, paraffin-embedded tissue, required
排除标准
- •Has nonsquamous NSCLC (adenocarcinoma/large cell or other)
- •Has received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor
- •Has received previous chemotherapy for advanced NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 1 year prior to randomization)
- •Has undergone major surgery or received any investigational therapy in the 4 weeks prior to randomization
- •Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
- •Has brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants. Participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible
- •Has superior vena cava syndrome contraindicating hydration
- •Has current clinically-relevant coronary artery disease or uncontrolled congestive heart failure
- •Has experienced myocardial infarction within 6 months prior to randomization
- •Has an ongoing or active infection (requiring antibiotics), including active tuberculosis or known infection with the human immunodeficiency virus
- •Has a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder
- •Has any National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0 Grade ≥ 2 peripheral neuropathy
- •Has significant third space fluid retention, requiring repeated drainage
- •Has any other serious uncontrolled medical disorders or psychological conditions that would, in the opinion of the investigator, limit the participant's ability to complete the study or sign an informed consent document
- •Has a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab (IMC-11F8), or any other contraindication to one of the administered treatments
- •Is pregnant or breastfeeding
- •Has a known history of drug abuse
- •Has a concurrent active malignancy other than adequately-treated basal cell carcinoma of the skin or preinvasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years
研究组 & 干预措施
Necitumumab + Gemcitabine + Cisplatin
Necitumumab: 800 milligrams (mg) I.V. infusion on Days 1 and 8 of every 3 week cycle.
Continues until progressive disease, toxicity, noncompliance, or withdrawal.
Gemcitabine: 1250 milligrams/square meter (mg/m2) on Days 1 and 8 of every 3 week cycle.
Continues for a maximum of six cycles.
Cisplatin: 75 mg/m2 IV on Day 1 of every 3 week cycle. Continues for a maximum of six cycles.
干预措施: Necitumumab (Biological)
Necitumumab + Gemcitabine + Cisplatin
Necitumumab: 800 milligrams (mg) I.V. infusion on Days 1 and 8 of every 3 week cycle.
Continues until progressive disease, toxicity, noncompliance, or withdrawal.
Gemcitabine: 1250 milligrams/square meter (mg/m2) on Days 1 and 8 of every 3 week cycle.
Continues for a maximum of six cycles.
Cisplatin: 75 mg/m2 IV on Day 1 of every 3 week cycle. Continues for a maximum of six cycles.
干预措施: Gemcitabine (Drug)
Necitumumab + Gemcitabine + Cisplatin
Necitumumab: 800 milligrams (mg) I.V. infusion on Days 1 and 8 of every 3 week cycle.
Continues until progressive disease, toxicity, noncompliance, or withdrawal.
Gemcitabine: 1250 milligrams/square meter (mg/m2) on Days 1 and 8 of every 3 week cycle.
Continues for a maximum of six cycles.
Cisplatin: 75 mg/m2 IV on Day 1 of every 3 week cycle. Continues for a maximum of six cycles.
干预措施: Cisplatin (Drug)
Gemcitabine + Cisplatin
Gemcitabine: 1250 mg/m2 on Days 1 and 8 of every 3 week cycle. Continues for a maximum of six cycles.
Cisplatin: 75 mg/m2 IV on Day 1 of every 3 week cycle. Continues for a maximum of six cycles.
干预措施: Gemcitabine (Drug)
Gemcitabine + Cisplatin
Gemcitabine: 1250 mg/m2 on Days 1 and 8 of every 3 week cycle. Continues for a maximum of six cycles.
Cisplatin: 75 mg/m2 IV on Day 1 of every 3 week cycle. Continues for a maximum of six cycles.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Overall Survival Time (OS)
时间窗: Randomization to Death from Any Cause (Up to 31 Months)
Overall survival is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated by the Kaplan-Meier method.
次要结局
- Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab(Day 1 of Cycle 2, 3, 4, 5 and 6 Prior to Necitumumab Drug Infusion, Up to 24 Months)
- Progression-Free Survival (PFS)(Randomization to Measured Progressive Disease or Death from Any Cause (Up to 31 Months))
- Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])(Baseline to Measured Progressive Disease (Up to 31 Months))
- Mean Change From Baseline in PRO Using the Outcomes Lung Cancer Symptom Scale (LCSS)(Baseline, Cycle 6 (Cycle = 3 Weeks))
- Number of Participants With a Serum Anti-Necitumumab Antibody Assessment(Baseline through 31 Months)
- Time to Treatment Failure (TTF)(Randomization to Measured Progressive Disease, Death From Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 31 Months))
- Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimension (EQ-5D)(Baseline, Cycle 6 (Cycle = 3 Weeks))
- Number of Participants With an Epidermal Growth Factor Hormone (EGFR) Protein Expression Measured by Immunohistochemistry (IHC)(31 Months)