Phase I/II Study of Polyphenon E in Addition to Erlotinib in Advanced Non Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Phase 1: Number of Participants with Adverse Events.
研究概览
简要总结
The purpose of this study is to study if the addition of the green tea extract, Polyphenon E, to Erlotinib is safe and if it has potential to improve outcomes in second line therapy for Advanced Stage IIIb/IV Non-small cell lung cancer.
详细描述
To evaluate the short term effects of Polyphenon E administered alone and in combination with erlotinib to patients with advanced Stage IIIB or IV Non Small Cell Lung Cancer (NSCLC) that has progressed after first line chemotherapy. We will do a Phase I dose escalation study with Polyphenon E and a fixed dose of erlotinib to evaluate for any significant adverse events related to the combination.
Once the maximum tolerated dose (MTD) of Polyphenon E has been established the Phase II trial will be embarked upon using this dose in combination with erlotinib. In both the Phase I and Phase II parts the agents will administered until time of progression or unacceptable side effects occur.
The primary end point of the Phase I part is establishing the safety, tolerability and MTD of Polyphenon E in combination with erlotinib given at 150mg per day.
The Primary endpoint of the Phase II part that will be studied is Response rate (RR) to the combination. Progression free survival (PFS), Overall Survival (OS) and the safety and tolerability of Polyphenon E in addition to erlotinib in this subject population and setting will be assessed as secondary objectives.
Changes in serum markers related to progression of cancer will also be studied as part of the Phase I and phase II study. The effect of Polyphenon E with or without erlotinib on the serum levels of circulating c-met RNA, Interleukin-8 (Il-8), Hepatocyte Growth Factor (HGF) and Vascular Endothelial Growth Factor (VEGF) will be studied as secondary objectives. Epidermal Growth Factor Receptor (EGFR) expression of the initial tumor tissue and testing for EGFR mutations in the tumor tissue and serum DNA and evaluation of "KIRSTEN RAT SARCOMA VIRAL ONCOGENE HOMOLOG" (KRAS) mutations with correlation of these results with treatment outcome will also be undertaken as secondary objectives in both the Phase I and II parts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Biopsy proven NSCLC
- •Stage IIIB or IV measurable disease burden after routine staging work up.
- •Documented disease progression after first or second line chemotherapy. This will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST)
- •Ability to give informed consent and willingness to adhere to study protocol
- •Ability to take oral medication
- •Age ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status between 0-2
- •Adequate hematological, hepatic and renal function defined as below:
- •granulocyte count > 1500/mm3, platelet count > 100.000/mm3, serum creatinine < 1.5; bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) at or below institutional upper limit of normal (IULN). All lab values should be obtained within 14 days of registration.
- •Patients have to have recovered from any toxic effects of prior chemotherapy or radiation therapy to a Grade 1 or less (except from alopecia). Enrollment should occur no less than 28 days after completion of prior therapy.
- •Ability to comply with the use of contraceptive measures starting 1 week before and ending 2 weeks after the last dose of study drug.
排除标准
- •Liver or kidney problems that would interfere with metabolism of study drug. This includes any preexisting elevation of AST, ALT, ALP or bilirubin.
- •Any condition that would hamper informed consent or ability to comply with the study protocol
- •Participation in another research study in the last three months
- •Known malignancy at any site other than NSCLC
- •Recent consumption of green tea (5 or more cups per day within one week of study enrollment)
- •Significant history of cardiac disease, e.g. uncontrolled hypertension, unstable angina, congestive-heart failure, myocardial infarction within the last six months or ventricular arrhythmias requiring medication.
- •Presence of metastatic brain lesions
- •Documented history of bleeding diathesis
- •Need to be on therapeutic anticoagulation
- •Pregnant and lactating women
- •Patients with a known seizure disorder who are taking Phenytoin, Carbamazepine or Phenobarbital
- •Patients taking medications known to interfere with erlotinib metabolism as listed below.
- •Atazanavir
- •Clarithromycin
- •Indinavir
- •Itraconazole
- •Ketoconazole
- •Nefazodone
- •Nelfinavir
- •Ritonavir
- •Saquinavir
- •Telithromycin
- •Troleandomycin
- •Voriconazole
- •Rifampicin
- •Rifabutin
- •Rifapentine
- •Phenytoin
- •Carbamazepine
- •Phenobarbital
- •St John's Wort.
研究组 & 干预措施
Phase I/II
Phase I: Polyphenon E + Erlotinib - Polyphenon E 200, 400 and 800 mg/day dose levels evaluated in a step-wise manner with Erlotinib 150 mg/day to establish Maximum Tolerated Dose (MTD) of Polyphenon E. Phase II consists of MTD of Polyphenon E established in Phase I, administered alone for two weeks and thereafter together with Erlotinib 150 mg/day.
干预措施: Polyphenon E (Drug)
Phase I/II
Phase I: Polyphenon E + Erlotinib - Polyphenon E 200, 400 and 800 mg/day dose levels evaluated in a step-wise manner with Erlotinib 150 mg/day to establish Maximum Tolerated Dose (MTD) of Polyphenon E. Phase II consists of MTD of Polyphenon E established in Phase I, administered alone for two weeks and thereafter together with Erlotinib 150 mg/day.
干预措施: Tarceva (Drug)
结局指标
主要结局
Phase 1: Number of Participants with Adverse Events.
时间窗: At Screening and every week for first 4 weeks and then week 6, 8 and then every 4 weeks in Phase I study. Liver function tests will be monitored at least every 4 weeks as applicable. The patients will be followed up to 2 years on average.
Toxicity evaluation of all adverse events monitored by physical exam, weight, vital signs, Complete Blood Count (CBC), Complete Metabolic Panel (CMP), coagulation panel and Computed Tomography (CT) scans of the chest, abdomen and pelvis, CT/Magnetic Resonance Imaging (MRI) of the head.
Phase 1: Maximum Tolerated Dose
时间窗: Day 1 of Phase I until progression, death or intolerable side effects would occur. The patients will be followed up to 2 years on average.
Dose-Limiting Toxicity (DLT) is defined as two or more events with grade 3 toxicity or a single event with grade 4-5 toxicity possibly or probably related to the study medications at a specific dose of Polyphenon E.
Phase 2: Response Rate
时间窗: Start of Phase 2 to until progression, death or intolerable side effects occur. The patients will be followed up to 2 years on average.
Response Rate defined as Complete (CR) + Partial Response (PR) using RECIST criteria. Complete response (CR): Complete disappearance of all measurable and non-measurable disease, no new lesions, no disease related symptoms, and normalization of markers and other abnormal lab values. All disease must be assessed using the same technique as baseline. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.
次要结局
- Phase 2: Correlation between level of EGFR expression on the original tumor tissue and the presence of EGFR mutations in exons 18, 19 and 21 in serum DNA and original tumor tissue with the treatment response and outcome.(Pre-study until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.)
- Phase 2: Correlation of KRAS mutations (in exons 2 and 3) in the original tumor tissue with treatment response and outcome.(Pre-study until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.)
- Phase I: Response rate(From registration until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.)
- Phase 1: Progression Free Survival(From registration until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.)
- Phase 2: Progression Free Survival(From registration until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.)
- Phase 2: Overall Survival(From registration until progression or intolerable side effects occur. The patients will be followed up to 2 years on average.)
研究者
Glenn Mills
Professor of Medicine
Louisiana State University Health Sciences Center Shreveport