Phase II Study of RAD001 Plus Octreotide Depot in Patients With Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma (Carcinoid, Islet Cell)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
Objectives:
Primary endpoint:
-Assess the clinical activity of RAD 001 plus depot octreotide as defined by progression free survival (PFS) duration defined by RECIST criteria in treated and untreated patients with metastatic, unresectable low grade neuroendocrine carcinoma.
Secondary endpoints:
- Assess the progression free survival duration of patients with metastatic, unresectable low grade neuroendocrine carcinoma treated with RAD 001 plus depot octreotide.
- Assess the safety of RAD 001 plus depot octreotide in patients with metastatic, unresectable low grade neuroendocrine carcinoma.
- To determine the expression/phosphorylation status of the components of the mTOR signaling pathway in the primary tumors, in order to determine whether these markers can be used as predictors of sensitivity to the combination of RAD001 and octreotide.
- To determine the effect of the combination of RAD001 and octreotide on the expression and phosphorylation of mTOR's targets in the accessible tumor tissue, in order to identify potential pharmacodynamics markers of response to this drug combination.
- To observe the effects of treatment with RAD001 on plasma angiogenic biomarkers.
详细描述
RAD001 is a new drug that is designed to block a protein that is important in the growth of cancer cells. Octreotide Depot is FDA approved for the treatment of carcinoid syndrome and hormonal symptoms from certain islet cell carcinomas. Octreotide Depot may also help to block certain proteins that are important in tumor growth.
Before you can start treatment on the study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will be asked questions about your medical history and about any medications you are currently taking or have taken in the past. You will have a complete physical exam and your heart rate, temperature, breathing rate, blood pressure, height, and weight will be measured. You will be asked about your ability to perform every day activities. Blood (about 2 teaspoons) will be collected for routine tests. You will have an electrocardiogram (ECG - a test that measures the electrical activity of the heart) and scans (either Computed Tomography/CT or Magnetic Resonance Imaging/MRI) to evaluate the cancer. Women who are able to have children must have a negative blood pregnancy test.
If the screening evaluations show you are eligible to take part in the study, you may begin treatment. You will take RAD001 by mouth once a day, every day while on study. You should take it in a fasting state or after no more than a light, fat-free meal. You should take RAD001 about the same time each day. Octreotide Depot will be given as an injection into the muscle of either buttock once every 4 weeks while on study. This will be done at M. D. Anderson. Four weeks (28 days) is called one course of treatment.
Clinic visits will occur every 2 weeks during the first 4 weeks and every 4 weeks from then on. At each clinic visit, you will be asked questions about your medical history and about any medications you are currently taking or have taken in the past. You will have a complete physical exam and your heart rate, temperature, breathing rate, blood pressure, height, and weight will be measured. You will be asked about your ability to perform every day activities. Blood samples (about 1 teaspoons) for routine tests will be collected every 2 weeks for the first 8 weeks. After that, blood samples (about 2 teaspoons) will be collected every 4 weeks. CT or MRI scan(s) will be performed every 12 weeks.
If a sample of your tumor tissue that was removed previously is available, it will be analyzed for expression of proteins that may effect tumor growth. However, if a sample is not available, you will not be asked to undergo a biopsy to collect this tissue. This sample may analyzed at any time during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patients with histologic proof of low grade neuroendocrine carcinoma will be eligible. Both carcinoid (any site[atypical/intermediate grade carcinoid is allowed]) and islet cell (pancreatic endocrine tumor) will be eligible.
- •Patients with neuroendocrine tumors associated with MEN1 syndrome will be eligible.
- •Patients must have either metastatic or unresectable local-regional cancer.
- •Patients must have measurable disease, as defined by RECIST (Response Evaluation Criteria In Solid Tumors).
- •Prior and concurrent octreotide (Sandostatin and Sandostatin LAR) is allowed.
- •Prior radiation therapy is permitted. A recovery period of at least 4 weeks after completion of radiotherapy is required prior to enrollment.
- •Patients may have received 0, 1, or 2 prior cytotoxic chemotherapy.
- •Chemotherapy used as a radiosensitizer will be considered one prior chemotherapy regimen.
- •Patients may have received prior interferon (not counted toward prior cytotoxic chemotherapy).
- •Patients may have received prior therapy targeting c-kit, abl, PDGFR (Platelet Derived Growth Factor Receptor), VEGF (Vascular endothelial growth factor), or EGFR [epidermal growth factor receptor] (not counted toward prior cytotoxic chemotherapy).
- •Patients may have had prior hepatic artery embolization. There must be residual measurable disease. Chemoembolization will be considered as one prior chemotherapy regimen.
- •Patients must have a performance status of 0, 1, or 2 (Zubrod scale).
- •Patients must be >/= 18 years old (age limit due to lack of adequate safety data in younger patients).
- •Patients must give written informed consent.
- •Patients should have adequate organ function defined as follows: Absolute granulocytes > 1,500/mm3, hemoglobin > 8 g/dl, and platelets > 100,000/mm
- •Serum bilirubin < 1.5 x Upper Limit of Normal (ULN), serum creatinine < 1.5 mg/dL, AST (SGOT) less/equal 2.5 x ULN, ALT (SGPT) less/equal 2.5 x ULN.
- •Patients must have recovered from recent surgery. One week must have elapsed from the time of a minor surgery and 4 weeks from major surgery.
- •Fertile patients, both male and female, must practice contraception during treatment.
排除标准
- •Patients may receive no other concurrent chemotherapy, immunotherapy, or radiotherapy.
- •Patients with intolerance to octreotide.
- •Patients who have received chemotherapy, immunotherapy, or investigational therapy in the 30 days prior to registration.
- •Patients with uncontrolled diabetes mellitus as defined by fasting blood sugar > 1.5 x ULN.
- •Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test prior to entry into the study. All patients of child-bearing potential must be advised of the importance of avoiding pregnancy and using appropriate methods of contraception while participating in this investigational trial. Women who have had menses within the past 2 years, who have not had a tubal ligation, or bilateral oophorectomy are considered to be of child-bearing potential. Appropriate methods of contraception include hormonal or barrier method of birth control; abstinence.
- •Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
- •Psychiatric disorders rendering them incapable of complying with the requirements of the protocol.
- •Osseous metastasis as only site of disease.
- •Any concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix. Patients with previous malignancies but without evidence of disease for > 5 years will be allowed to enter the trial.
研究组 & 干预措施
RAD001 plus Depot Octreotide
RAD001 at 5 or 10 milligrams orally once a day plus Octreotide Depot 30 milligrams intramuscularly once every 28 days.
干预措施: RAD001 (Drug)
RAD001 plus Depot Octreotide
RAD001 at 5 or 10 milligrams orally once a day plus Octreotide Depot 30 milligrams intramuscularly once every 28 days.
干预措施: Octreotide Depot (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: PFS assessed every 12 weeks (at the end of every 3 cycles) or more frequently if clinically indicated
PFS is measured from date of trial entry until documented progression of disease or death from any cause. PFS is measured by computed tomography (CT) scans or magnetic resonance imaging (MRI) performed at baseline and after every three cycles.
次要结局
未报告次要终点