Cisplatin + Etoposide +/- Concurrent ZD6474 in Previously Untreated Extensive Stage Small Cell Lung Cancer
2020年2月7日 更新者：Hoosier Cancer Research Network
A Randomized Double Blind Phase II Trial of Cisplatin Plus Etoposide With/Without Concurrent ZD6474 in Patients With Previously Untreated Extensive Stage Small Cell Lung Cancer: Hoosier Oncology Group LUN06-113
At this point in the treatment of extensive stage SCLC, we have reached a plateau in survival with conventional chemotherapy and newer regimens are greatly needed.
It has been noted that patients with increased VEGF levels have a poorer prognosis.
Anti-angiogenic agents hold significant promise in the treatment of patients with extensive stage SCLC.
ZD6474, a new inhibitor of the VEGFR-2, has shown favorable action in NSCLC.
研究概览
详细说明
OUTLINE: This is a multi-center study.
Arm A:
Cisplatin 60mg/m2 Day 1 + Etoposide 120mg/m2 Day 1,2,3 + Placebo oral daily given continuously for the duration of the study
Arm B:
Cisplatin 60mg/m2 Day 1 + Etoposide 120mg/m2 Day 1,2,3 + ZD6474 100mg oral daily given continuously for the duration of the study
For both arms, PE and toxicity evaluation prior to each cycle and disease assessment by imaging every 2 cycles. Patients with non-PD and acceptable toxicity will continue protocol therapy; patients with progressive disease or excessive toxicity will be taken off treatment. Cycles will be repeated every 21 days up to a total of 4 cycles.
ECOG Performance Status of 0 or 1
Life Expectancy: Not specified
Hematopoietic:
- Platelets > 100K/mm3
- Absolute neutrophil count (ANC) > 1.5K/mm3
Hepatic:
- Bilirubin < 1.5 x ULN
- Aspartate aminotransferase (AST) < 2.5 x ULN or < 5 x ULN if judged by the investigator to be related to liver metastases
- Alkaline phosphatase < 2.5 x ULN or < 5 x ULN if judged by the investigator to be related to liver metastases
Renal:
- Serum creatinine < 1.5 x ULN or Calculated creatinine clearance of > 45 cc/min using the Cockcroft-Gault formula
Cardiovascular:
- No clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >2 (see SPM) within 3 months prior to registration for protocol therapy
- No presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
- No history of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is permitted.
研究类型
介入性
注册 (实际的)
74
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Delaware
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Newark、Delaware、美国、19713
- Helen F. Graham Cancer Center
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Illinois
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Chicago、Illinois、美国、60611
- Northwestern University Feinberg School of Medicine
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Galesburg、Illinois、美国、61401
- Medical & Surgical Specialists, LLC
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Indiana
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Bloomington、Indiana、美国、47403
- Cancer Care Center of Southern Indiana
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Evansville、Indiana、美国、47714
- Oncology Hematology Associates of SW Indiana
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Fort Wayne、Indiana、美国、46815
- Fort Wayne Oncology & Hematology, Inc
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Indianapolis、Indiana、美国、46202
- Indiana University Simon Cancer Center
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Indianapolis、Indiana、美国、46202
- IN Onc/Hem Associates
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Indianapolis、Indiana、美国、46206
- St. Vincent Hospital & Health Centers
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Lafayette、Indiana、美国、47904
- IU Health Arnett Cancer Center
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Lafayette、Indiana、美国、47905
- Horizon Oncology Researcg
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Muncie、Indiana、美国、47303
- IU Health at Ball Memorial Hospital
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Munster、Indiana、美国、46321
- Monroe Medical Associates
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South Bend、Indiana、美国、46601
- Northern Indiana Cancer Research Consortium
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Terre Haute、Indiana、美国、47802
- Providence Medical Group
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Nebraska
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Omaha、Nebraska、美国、68114
- Methodist Cancer Center
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New Jersey
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Mount Holly、New Jersey、美国、08060
- Hematology Oncology Associates S.J., P.A.
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Oregon
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Portland、Oregon、美国、97213
- Providence Portland Medical Center
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19106
- Pennsylvania Oncology-Hematology Associates
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Histological or cytological proof of chemotherapy-naïve, extensive, small cell lung cancer.
- Measurable disease according to RECIST and obtained by imaging within 28 days prior to being registered for protocol therapy.
- Written informed consent and HIPAA authorization for release of personal health information.
- Age 18 years or older at the time of consent.
- Potassium ≥4.0 mmol/L and <5.5mmol/L (supplementation is allowed).
- Calcium within normal range (supplementation is allowed).
- Magnesium within normal range (supplementation is allowed).
Exclusion Criteria:
- No prior EGFR inhibitor or antiangiogenic agent allowed.
- No prior hormonal therapy.
- No symptomatic brain metastasis.
- No clinically significant infections as judged by the treating investigator.
- No evidence of severe or uncontrolled other systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
- No previous history of QTc prolongation as a result of medication that required discontinuation of that medication.
- No congenital long QT syndrome or known 1st degree relative with unexplained sudden death under 40 years of age.
- No presence of left bundle branch block (LBBB.)
- No QTc with Bazett's correction that is unmeasurable, or ≥480 msec on screening ECG obtained within 7 days prior to registration for protocol therapy. If a subject has QTc ≥480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the subject to be eligible for the study.
- No concomitant (within 14 days prior to registration for and during protocol therapy) medication associated with Torsades de Pointes or cause QTc prolongation, is allowed. Medications that prolong QT, but are not strictly associated with Torsades, are allowed if medically necessary and will require increased ECG and electrolyte monitoring.
- No uncontrolled hypertension (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg).
- No currently active diarrhea that may affect the ability to absorb ZD6474.
- No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the subject has been disease-free for at least 5 years.
- Major surgery must be completed greater than 28 days prior to registration for protocol therapy and healed surgical incision is required.
- No concomitant (within 14 days prior to registration for and during protocol therapy) medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function.
- Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation.
- Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
- Females must not be breastfeeding.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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安慰剂比较：Arm A: ZD6474 Matched Placebo
Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 matched placebo oral daily to be continued for the duration of the study.
Prophylactic antiemetics will be given at the discretion of the treating investigator.
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Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles
Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles
Matched placebo oral daily
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有源比较器：Arm B: ZD6474
Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study.
Prophylactic antiemetics will be given at the discretion of the treating investigator.
|
Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles
Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles
ZD6474 100mg oral daily to be continued for the duration of the study.
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实验性的：Safety Lead-In
Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study.
Prophylactic antiemetics will be given at the discretion of the treating investigator.
The safety lead-in will be conducted to determine the safety of the combination of ZD6474 and cisplation + etopiside.
If this combination is found to be unsafe, no patients will be randomized in the Phase II portion of the trial.
If the combination is deemed safe according to the protocol, participants from the safety lead-in cohort will not be included in the efficacy analysis.
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Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles
Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles
ZD6474 100mg oral daily to be continued for the duration of the study.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Time to Disease Progression - Median Time to Progression and Log-Rank Test
大体时间：24 months
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Kaplan-Meier analysis comparing arm A to arm B. Median time to progression and log-rank test.
Safety lead-in participants are not included in this analysis per protocol.
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24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Percentage of Participants With Grade 3/4 Hematologic and Non-Hematologic Toxicities
大体时间：6 weeks (2 Cycles)
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Percentage of participants who experienced grade 3/4 hematologic and non-hematologic toxicities.
Participants from Arm A were compared to subjects from Arm B + Safety Lead-In.
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6 weeks (2 Cycles)
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Measure the Response Rate (CR + PR) in Each Arm
大体时间：24 months
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Response assessments completed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST Therasse et al., 2000).
Complete Response (CR) is defined as: Disappearance of all target lesions.
Partial Response (PR) is defined as: >=30% decrease in the sum of the longest diameter of target lesions.
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24 months
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Measure Disease Control Rate (CR + PR+ SD) in Each Arm
大体时间：24 months
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Response assessments completed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST Therasse et al., 2000).
Complete Response (CR) is defined as: Disappearance of all target lesions.
Partial Response (PR) is defined as: >=30% decrease in the sum of the longest diameter of target lesions.
Stable Disease (SD) is defined as: neither a partial response or progressive disease ( >=20% increase in the sum of the longest diameter of the target lesions).
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24 months
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Measure Overall Survival for Each Arm
大体时间：24 months
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24 months
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Assess VEGF Polymorphisms and Correlate Subject Response
大体时间：24 months
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24 months
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
调查人员
- 学习椅：Nasser Hanna, M.D.、Hoosier Oncology Group, Inc.
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2008年1月1日
初级完成 (实际的)
2015年8月1日
研究完成 (实际的)
2015年8月1日
研究注册日期
首次提交
2008年1月31日
首先提交符合 QC 标准的
2008年1月31日
首次发布 (估计)
2008年2月13日
研究记录更新
最后更新发布 (实际的)
2020年2月11日
上次提交的符合 QC 标准的更新
2020年2月7日
最后验证
2020年2月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.