A Phase II Evaluation of AZD6244 (NSC #748727) in the Treatment of Recurrent or Persistent Endometrial Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 72
- 主要终点
- Number of Participants With or Without Progression-free Survival for > 6 Months by Response Evaluation Criteria for Solid Tumors (RECIST)
研究概览
简要总结
This phase II trial is studying how well selumetinib works in treating patients with recurrent or persistent endometrial cancer that has come back or is persistent. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To assess the activity of AZD6244 (selumetinib) for patients with recurrent or persistent endometrial cancer with the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response.
II. To determine the nature and degree of toxicity of AZD6244 as assessed by CTCAE v3.0 in this cohort of patients.
SECONDARY OBJECTIVE:
I. To determine the duration of progression-free survival and overall survival.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed* endometrial epithelial carcinoma, including any of the following cell types:
- •Endometrioid adenocarcinoma
- •Serous adenocarcinoma
- •Undifferentiated carcinoma
- •Clear cell adenocarcinoma
- •Mixed epithelial carcinoma
- •Adenocarcinoma not otherwise specified
- •Mucinous adenocarcinoma
- •Squamous cell carcinoma
- •Transitional cell carcinoma
- •Mesonephric carcinoma
- •Recurrent or persistent disease that is refractory to curative therapy or established treatments
- •Measurable disease, defined as ≥ 1 lesion that can be measured in ≥ 1 dimension (longest dimension to be recorded)
- •Each lesion must be ≥ 20 mm when measured by conventional techniques (palpation, plain x-ray, CT scan, or MRI) OR ≥ 10 mm when measured by spiral CT scan
- •Must have ≥ 1 target lesion to be used to assess response, as defined by RECIST criteria
- •Tumors within a previously irradiated field are designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days following completion of radiotherapy
- •Must have received 1 prior chemotherapeutic regimen for the management of endometrial carcinoma
- •Chemotherapy administered as a radiosensitizer in conjunction with primary radiotherapy is considered a systemic chemotherapy regimen
- •Not eligible for a higher priority GOG protocol, if one exists (e.g., any active phase III GOG protocol for the same patient population)
- •No prior or concurrent CNS disease (treated or untreated) by physical examination, including primary brain tumor or brain metastases
- •GOG performance status (PS) 0-2 (for patients who received 1 prior treatment regimen)
- •GOG PS 0-1 (for patients who received 2 prior treatment regimens)
- •ANC ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Creatinine ≤ 1.5 times upper limit of normal (ULN)
- •Bilirubin ≤ 1.5 times ULN
- •SGOT ≤ 2.5 times ULN
- •Alkaline phosphatase ≤ 2.5 times ULN
- •PT/INR ≤ 1.5 OR in-range INR (between 2 and 3) if patient is on a stable dose of therapeutic warfarin
- •PTT ≤ 1.5 times ULN
- •Oxygen saturation ≥ 88% on room air
- •QTc < 450 msec by EKG
- •LVEF normal
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
- •No neuropathy (sensory or motor) > grade 1
- •No active infection requiring antibiotics
- •Uncomplicated urinary tract infection allowed
- •No other invasive malignancy within the past 5 years except for nonmelanoma skin cancer
- •No serious, non-healing wound, ulcer, or bone fracture
- •No history of abdominal fistula or gastrointestinal perforation
- •No intra-abdominal abscess within the past 28 days
- •No active bleeding or pathological condition that would carry a high risk of bleeding (e.g., bleeding disorder, coagulopathy, or tumor involving major vessels)
- •No seizures not controlled with standard medical therapy
- •No clinically significant cardiovascular disease including, but not limited to, any of the following:
- •Uncontrolled hypertension, defined as systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg
- •Myocardial infarction or unstable angina within the past 6 months
- •NYHA class II-IV congestive heart failure
- •Serious cardiac arrhythmia requiring medication, including atrial fibrillation requiring rate-controlling medication
- 另有 19 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (selumetinib)
Patients receive selumetinib PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood and archived tumor tissue samples are collected for biomarker studies.
干预措施: Diagnostic Laboratory Biomarker Analysis (Other)
Treatment (selumetinib)
Patients receive selumetinib PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood and archived tumor tissue samples are collected for biomarker studies.
干预措施: Selumetinib (Drug)
结局指标
主要结局
Number of Participants With or Without Progression-free Survival for > 6 Months by Response Evaluation Criteria for Solid Tumors (RECIST)
时间窗: > 6 months from study entry
Number of participants who survived progression-free for more than 6 months. Progression is defined using Response Evaluation Criteria for Solid Tumors (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions in the opinion of the treating physician, or global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression.
Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0
时间窗: Each cycle during treatment and 30 days after the last treatment.
Objective Tumor Response Rate Assessed by RECIST
时间窗: From study entry, assessed up to 5 years
Per Response Evaluation Criteria In Solid Tumors (RECIST) Criteria: Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Normalization of CA125, if elevated at study entry, is required; Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry; Stable Disease is any condition not meeting the above criteria.
次要结局
- Duration of Progression-free Survival(Every other cycle for the first 6 months; then every 3 months thereafter for up to 5 years)
- Duration of Overall Survival(Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.)