Phase II/III Study to Evaluate the Safety and Efficacy of Sirolimus for Injection (Albumin Bound) Combined With Octreotide Long-acting Injection in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 298
- 试验地点
- 1
- 主要终点
- Phase II: Incidences of Adeverse Events (AEs)
研究概览
简要总结
There is limited evidence regarding the benefit of adding somatostatin analogs to molecular targeted agents for well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with poor prognostic factors. This trial is conducted to evaluate sirolimus for injection (albumin bound) combined with octreotide long-acting injection in patients with unresectable or recurrent GEP-NETs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •1. Unresectable locally advanced or metastatic G1/G2 GEP-NETs diagnosed by histology, according to the 2019 WHO histological grading criteria.
- •2. Having poor prognostic factors.
- •3. Non-functional GEP-NETs are required.
- •4. At least one evaluable lesion meets the RECIST V1.1 standard (Applicable only to the phase II safety run-in stage)
- •6. ECOG 0~
- •7. Organ function reserve is good.
- •8. Be able to sign a written informed consent form.
排除标准
- •1. Patients who have previously received SSTR-targeted therapies (including somatostatin analogs [SSAs] and peptide receptor radionuclide therapy) and/or mTOR inhibitors (Patients who received SSAs in the adjuvant setting and experienced recurrence ≥6 months after treatment completion may be enrolled)[ Applicable to Phase II dose expansion and Phase III stages].
- •2. Has uncontrolled/severe diarrhea or an axillary temperature > 38.0°C at enrollment.
- •3. Received treatment with other unlisted clinical investigational drugs within 4 weeks prior to the first use of the investigational drug.
- •4. Undergone major surgical procedures within 4 weeks prior to the first use of the investigational drug and have not fully recovered.
- •5. Received systemic use of corticosteroids or other immunosuppressive therapy within 2 weeks prior to the first use of the study drug.
- •6. With an infection that requires systemic anti-infective treatment within 2 weeks prior to the first use of the study drug.
- •7. Those who have used strong inhibitors or inducers of CYP3A4 liver metabolic enzymes within 2 weeks prior to the first use of the investigational drug or still need to continue using such drugs.
- •8. Has a serious history of cardiovascular and cerebrovascular diseases.
- •9. Having active brain metastasis and/or malignant meningitis.
- •10. With a history of severe lung diseases.
- •11. During screening, there may be symptomatic gallstones or a history of symptomatic gallstones but no surgical treatment has been performed.
- •12. Abnormal thyroid function during screening.
- •13. Known to have hypersensitivity reactions or intolerance to any component of all investigational drugs or their excipients.
- •14. Active hepatitis B, active hepatitis C virus infection, or active syphilis infection.
- •15. History of autoimmune diseases (excluding tuberous sclerosis), history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
研究组 & 干预措施
Everolimus monotherapy
Everolimus (QD) will be orally administrated on a 28-day cycle. Only for Phase III
干预措施: Everolimus (Drug)
Sirolimus combined with octreotide
Sirolimus for injection (albumin bound) combined with octreotide long-acting injection will be administrated on a 28-day cycle
干预措施: Sirolimus for injection (albumin bound) (Drug)
Sirolimus combined with octreotide
Sirolimus for injection (albumin bound) combined with octreotide long-acting injection will be administrated on a 28-day cycle
干预措施: Octreotide long-acting injection (Drug)
Sirolimus monotherapy
Sirolimus for injection (albumin bound) will be administrated on a 28-day cycle.
干预措施: Sirolimus for injection (albumin bound) (Drug)
结局指标
主要结局
Phase II: Incidences of Adeverse Events (AEs)
时间窗: Up to 3 years
Phase II: Maximum tolerated dose (DLT)
时间窗: Up to 1 year
Phase II: Objective Response Rate (ORR） per investigator
时间窗: Up to 1 year
Phase II: Recommended Phase 3 Dose (RP3D)
时间窗: Up to 1 year
Phase III: Progression Free Survival (PFS) per Independent Review Committee (IRC)
时间窗: Up to 3 years
Phase III: Progression Free Survival (PFS) per Blinded Independent Review Committee (BIRC)
时间窗: Up to 3 years
Phase II: Dose Limiting Toxicity (DLT)
时间窗: Up to 1 year
次要结局
- Phase II: Progression Free Survival (PFS) per investigator(Up to 3 years)
- Phase II: Duration of Response (DOR) per investigator(Up to 3 years)
- Phase II: Disease Control Rate (DCR) per investigator(Up to 3 years)
- Phase III: Duration of Response (DOR)(Up to 3 years)
- Phase III: Disease Control Rate (DCR)(Up to 3 years)
- Phase II/III: Overall Survival (OS)(Up to 3 years)
- Peak Concentration：Cmax(Up to 3 years)
- Area under the plasma concentration-time curve: AUC(Up to 3 years)
- Half-Life: t1/2(Up to 3 years)
- Phase III: Progression Free Survival (PFS) per investigator(Up to 3 years)
- Phase III: Objective Response Rate (ORR）(Up to 3 years)
- Phase III: Incidences of Adeverse Events (AEs)(Up to 3 years)
- Phase II: Overall Survival (OS)(Up to 3 years)
- Phase II: Blood concentrations and PK parameters of sirolimus for injection(albumin bound) and Octreotide long-acting injection.(From first dose of treatment to C3D15)
- Phase II: Changes in serum chromogranin A, 24-hour urinary 5-hydroxyindoleacetic acid, and serum IGF-1 levels from baseline.(From first dose of treatment to end of treatment)
- Phase III: Overall Survival (OS)(Up to 3 years)
- Phase III: Changes in serum chromogranin A, 24-hour urinary 5-hydroxyindoleacetic acid, and serum IGF-1 levels from baseline.(From first dose of treatment to end of treatment)