PTK and Letrozole in Post-menopausal Women With Advanced Breast Cancer
Phase II Study of the Combination of PTK787/ZK222584 and Letrozole in Postmenopausal Women With Advanced Hormone Receptor Positive Breast Cancer
研究概览
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
-
-
Missouri
-
St. Louis、Missouri、美国、63110
- Washington University School of Medicine
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Postmenopausal women with metastatic breast cancer, or loco-regional disease recurrence not amenable to treatment by surgery or radiotherapy.
Postmenopausal status will be defined by any of the following criteria:
- no spontaneous menses for at least 5 years
- spontaneous menses within the past 5 years but amenorrheic for at least 12 months and estradiol and/or FSH values in the postmenopausal range (while off aromatase inhibitor therapy; levels can have been taken while on tamoxifen but in this case estradiol should be the parameter assessed)
- bilateral oophorectomy
- radiation castration and amenorrheic for at least 3 months
- the use of an LHRH agonist throughout the duration of the trial (for example goserelin 3.6 mg s.c. monthly)
- Age ≥ 18 years old
- Patients whose tumors are either estrogen-receptor (ER) and/or progesterone-receptor (PgR) positive (10% or more infiltrating cancer cells exhibiting nuclear staining). Patients will be regarded as ER or PgR positive as long as at least one of the tissues assessed was positive. A positive biochemical test is also acceptable.
- Patients must have a WHO Performance Status Grade 0-2
- Newly diagnosed patients who are initiating first line treatment or those patients with known disease who have shown resistance to anti- estrogen therapy (tamoxifen or toremifine).
- Patients currently receiving letrozole or alternative aromatase inhibitors as initial therapy who are without evidence of progressive disease are eligible.
- Patients with bone-only metastasis are eligible.
Laboratory values ≤ 2 weeks prior to randomization:
- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L (≥ 1500/mm3)
- Platelets (PLT) ≥ 100 x 109/L (≥ 100,000/mm3)
- Hemoglobin (Hgb) ≥ 9 g/dL
- Serum creatinine ≤ 1.5 ULN
- Serum bilirubin ≤ 1.5 ULN
- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 x ULN (≤ 5 x ULN if liver metastases present)
Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein
- 500 mg and measured creatinine clearance (CrCl) ≥ 50 mL/min from a 24- hour urine collection
- Life expectancy ≥ 12 weeks
- Written informed consent obtained according to local guidelines
Exclusion Criteria:
- Patients with tumors which are both estrogen and progesterone receptor negative, or estrogen receptor negative and progesterone receptor unknown or estrogen receptor unknown and progesterone receptor negative
- Patients with a history of adrenalectomy or hypophysectomy
- Patients who developed progressive disease while being treated with an aromatase inhibitor.
Patients with any of the following:
- Absolute Neutrophil Count < 1.5 x 109/L
- Hemoglobin < 9 g/dl
- Platelet count < 100 x 109/L
- AST and ALT > 3 times the upper limit of normal or > 5 times the upper limit of normal if liver metastasis are present
- Bilirubin > 1.5 upper limit of normal
- Creatinine > 1.5 x upper limit of normal
- Calcium > 11.6 mg/dL
- History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis)
- Patients with a history of another primary malignancy ≤ 5 years that has not been treated for curative intent or that the chance of long term remission is judged to be less than 50%.
- Prior chemotherapy <3 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities
- Prior biologic or immunotherapy ≤ 2 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities
- Patients with a history of treatment with Fulvestrant or Trastuzumab < 6 months prior to registration. Patients must have recovered from all therapy- related toxicities in order to be enrolled.
- Prior full field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease
- Major surgery (e.g., laparotomy) ≤ 4 weeks prior to randomization. Minor surgery ≤ 2 weeks prior to randomization. Insertion of a vascular access device is not considered major or minor surgery in this regard. Patients must have recovered from all surgery-related toxicities
- Patients who have received investigational drugs ≤ 4 weeks prior to registration and/or randomization
- Prior therapy with anti-VEGF agents
- Peripheral neuropathy with functional impairment ≥ CTC grade 2 neuropathy, regardless of causality
- Pleural effusion or ascites that causes respiratory compromise (≥ CTC grade 2 dyspnea)
Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
- Uncontrolled high blood pressure (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg), history of labile hypertension, or history of poor compliance with an antihypertensive regimen
- Unstable angina pectoris
- Symptomatic congestive heart failure
- Myocardial infarction ≤ 6 months prior to registration and/or randomization
- Serious uncontrolled cardiac arrhythmia
- Uncontrolled diabetes (fasting blood sugar > 300 mg/dl)
- Active or uncontrolled infection
- Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
- Patients with prolonged QTc > 470 msec on EKG. All patients with a history of congenital or acquired long QTc syndrome.
- Chronic renal disease
- Acute or chronic liver disease (e.g., hepatitis, cirrhosis)
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK 222584 (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets)
Patients with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if it is felt that:
1) a potential drug interaction between PTK787/ZK 222584 and any of the patient's anti-HIV medications could influence the efficacy of the anti-HIV medication, or 2) it may place the patient at risk due to the pharmacologic activity of PTK787/ZK 222584. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
- Patients who are taking therapeutic warfarin sodium (Coumadin) or similar oral anticoagulants that are metabolized by the cytochrome P450 system. Heparin in any formulation is allowed. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
- Patients on P450 enzyme inducing anti-epileptics
- Patients who are unwilling or unable to comply with protocol requirements.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:Letrozole + PTK787/ZK222584
Letrozole 2.5 mg PO daily for 28 days (patients who have already been treated with letrozole for at least 28 days can skip this part) Start cycle 1 with:
Subsequent cycles:
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Assess the effect of the combination of letrozole & PTK787/ZK222584 on disease progression.
大体时间:24 weeks after starting PTK787/ZK222584
|
24 weeks after starting PTK787/ZK222584
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Evaluate the response rate (CR and PR)
大体时间:Completion of treatment
|
Completion of treatment
|
|
Evaluate the safety and tolerability of the combination of drugs
大体时间:30 days after completion of study treatment
|
30 days after completion of study treatment
|
|
Evaluate the pharmacokinetic profiles of the combination of drugs
大体时间:Cycle 3 Day 1
|
Cycle 3 Day 1
|
|
Evaluate the modulation of tumor blood flow and blood vessel permeability in response to PTK787/ZK222584 when administered in combination with letrozole using Dynamic Contrast-Enhanced Magnetic Resonance Imaging
大体时间:Cycle 1 Day 28
|
Cycle 1 Day 28
|
|
Evaluate the effect on circulating tumor cells
大体时间:Completion of treatment
|
Determined by the commerical Immunocon cell search assay
|
Completion of treatment
|
Compare outcome of patients receiving letrozole and PTK787/ZK222584 (cases) with control patients from pivotal trials of letrozole in the first and second line setting.
大体时间:30 days after completion of study treatment
|
Matching the cases and controls for line of therapy, sites of disease and duration of prior aromatase inhibitor therapy before the study patient initiates PTK787/ZK222584 treatment.
|
30 days after completion of study treatment
|
Evaluate polymorphisms in relevant drug metabolism genes to determine the molecular basis for interactions between letrozole and PTK787/ZK222584 should they occur.
大体时间:Completion of treatment
|
Completion of treatment
|
|
Correlate serum LDH level with clinical response
大体时间:Completion of treatment
|
Completion of treatment
|
|
With additional patient consent, collect peripheral blood cells, serum, plasma, and representative tumor tissue specimens for future correlative science studies
大体时间:Baseline visit
|
Baseline visit
|
合作者和调查者
合作者
调查人员
- 首席研究员:Cynthia Ma, M.D., Ph.D.、Washington University School of Medicine
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
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.