A Phase II Study on Everolimus, an mTOR Inhibitor (Oral Formulation), With Octreotide LAR® in Adult Patients With Advanced, Non-functioning, Well-differentiated Gastrointestinal Neuroendocrine Tumours (GI NET)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Percentage of patients with progression-free survival (PFS)
研究概览
简要总结
The underlying hypothesis of the synergistic activity of octreotide and everolimus is based on the combination of a) a direct action of everolimus over mTOR (mammalian target of rapamycin), and b) the inhibitory effect of octreotide on the IGF-I (insulin like growth factor 1) system preventing the activation of the mTOR system by this factor. Both types of inhibition would completely cancel this signal transduction pathway, which is so important in neuroendocrine tumours.
Furthermore, the biological study proposed in this protocol will allow for better establishing the relationship between the activation of the IGFR-PI3K-mTOR signal transduction pathway (i.e., the mTOR pathway stimulated by IGFR) and treatment response; this information is relevant since the IGFR-PI3K-mTOR activation status could be a response prediction factor.
This study will provide significant additional information about the efficacy of the combination treatment of everolimus with octreotide LAR® in non-functioning GI NET.
详细描述
Everolimus has been developed following two administration regimens: weekly and daily. Phase I pharmacodynamic studies recommend doses of 50 mg weekly and 10 mg/daily, based on its toxicity and inhibitory effect of the mTOR pathway in tumours; although the inhibition of this pathway has been demonstrated, the knowledge of response prediction factors has not been developed, in part due to the very low responses found in the population in phase I studies. These factors can be better outlined in a phase II study, where patients who have received fewer previous treatments can respond better, and where the profile of responders and non-responders can be identified more easily.
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
- •Diagnosis of non-operable or metastatic non-functioning, well differentiated advanced GI NET, confirmed by cytology or histology. In case of liver metastasis, neuroendocrine tumours of unknown origin are accepted.
- •Confirmation of diagnosis of neuroendocrine carcinoma of low to intermediate histology grade
- •Radiologically documented disease progression within 12 months prior to inclusion in the study. If the patient received anticancer treatment within the past 12 months, disease progression must be documented by radiology during or after taking this medication
- •Adequate bone marrow. liver and renal function
排除标准
- •Previous treatment with mTOR inhibitors (sirolimus, temsirolimus, everolimus, deforolimus).
- •Patients with any serious disease and/or an uncontrolled clinical condition
- •Patients on chronic treatment with corticosteroids or any other immunosuppressive agent
研究组 & 干预措施
Everolimus + Octreotide LAR treatment
干预措施: Everolimus (Drug)
Everolimus + Octreotide LAR treatment
干预措施: octreotide LAR (Drug)
结局指标
主要结局
Percentage of patients with progression-free survival (PFS)
时间窗: After 12 month of study treatment
Rate of patients
次要结局
- Rate of patients with objective responses(Each three cycles)
- Median and average of time for Overall survival(At the end of the study)
- Number of patients positive for insulin like growth factor 1 receptor (IGF1R) and ribosomal kinase S6 (S6K) phosphorylation.(At baseline)
- Rate of patients with an early decrease of chromogranin A (CgA) levels(Each cycle)
- Percentage of patients with Adverse Events(Each cycle)