A Multi-center Clinical Study to Evaluate Dual mTORC1/2 Inhibitor (ATG 008) or Selective Inhibitor of Nuclear Export Compound (ATG-010) in Combination With Chemotherapy in Patients With Relapsed or Metastatic Ovarian Cancer, Endometrial Cancer, and Cervical Cancer
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Objective response rate(ORR)
研究概览
简要总结
- This is a multi-center clinical study to evaluate dual mTORC1/2 inhibitor (ATG 008) or selective inhibitor of nuclear export compound (ATG-010) in combination with chemotherapy in patients with relapsed or metastatic ovarian cancer, endometrial cancer, and cervical cancer.
详细描述
This is a multi-center clinical study to evaluate dual mTORC1/2 inhibitor (ATG 008) or selective inhibitor of nuclear export compound (ATG-010) in combination with chemotherapy in patients with relapsed or metastatic ovarian cancer, endometrial cancer, and cervical cancer. And two cohorts of ATG-008 30 mg QD or ATG-010 80 mg QW in combination with chemotherapy will enroll subjects with platinum-sensitive ovarian cancer, platinum-resistant ovarian cancer, endometrial cancer, and cervical cancer, with about 8-12 subjects in either cohort. A total of about 64-96 subjects plan to be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Understand and voluntarily sign informed consent (ICF).
- •Age 18 to 70 (including 18 and 70).
- •Histopathological or clinical diagnosis of high grade relapsed or metastatic serous ovarian cancer (including fallopian tube cancer and peritoneal cancer), endometrial cancer (including endometrial carcinosarcoma) and cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma); received ≤1 line treatment after recurrence.
- •At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Life expectancy >3 months.
- •Women of childbearing potential must agree to use effective contraceptives from signing the informed consent until 180 days after the last dose of study drug. Women of childbearing age include premenopausal women and women within 2 years after menopause. Women of childbearing age must have a negative blood pregnancy test at screening
排除标准
- •Histopathological diagnosis of sarcoma, carcinosarcoma (except endometrial carcinosarcoma).
- •Low-grade serous carcinoma, clear cell carcinoma, and mucinous carcinoma.
- •Symptomatic central nervous system metastases (except those who have been previously treated for brain metastases but have been keeping stable of disease status for 4 weeks prior to screening).
- •Participated in other clinical trials within 4 weeks prior to screening.
- •Received major surgery within 4 weeks prior to screening or expect to proceed a major surgical treatment during the study period.
- •Received systemic chemotherapy, radiotherapy, traditional Chinese medicine with anti tumor indications within 4 weeks prior to screening, or plan to receive therapeutic radiotherapy during the study period.
- •Received live attenuated vaccine within 4 weeks before screening, or plan to receive live attenuated vaccine during screening.
- •Using systemic immunosuppressive drugs currently or used within two weeks before screening with the following exceptions:
- •Intranasal, inhaled, topical steroid or topical steroid injection (eg, intraarticular),
- •Systemic corticosteroids at physiologic doses not to exceed 10 mg/ day of prednisone or equivalent, OR
- •Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication).
- •Suffer from swallowing dysfunction, active gastrointestinal diseases or other diseases or disorders that affect the absorption, distribution, metabolism, and excretion of ATG-008 or ATG
- •Hepatitis B virus (HBV) infection (Hepatitis B surface antigen [HBsAg] positive) or active hepatitis C virus (HCV) infection (HCVRNA positive at screening).
- •Subjects with a history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome.
- •Hypersensitive or known to be allergic to ATG-008, ATG-010 or chemotherapeutic agents or to active or inactive ingredients of drugs with similar chemical structures.
- •Have a history of organ transplantation (eg, liver transplantation or autologous stem cell transplantation).
- •Known as alcohol or drug dependent.
- •Female subjects who are pregnant or lactating.
- •Judgment by the investigator that the subject should not participate in the study by consideration of the complications or other conditions which might affect their adherence to the protocol.
研究组 & 干预措施
ATG-008 + Chemotherapeutics
ATG-008: Oral, 30 mg QD+Paclitaxel: 175 mg/m2, intravenous infusion >3 h, Day 1, Q3W; ATG-008: Oral, 30 mg QD+Carboplatin: AUC = 5, intravenous infusion >1 h, Day 1, Q3W or Cisplatin: 75 mg/m2, intravenous infusion >1h, Day 2, Q3W ; ATG-008: Oral, 30 mg QD+Doxorubicin hydrochloride liposome, 40 mg/m2, Day 1; Q4W;
干预措施: ATG-008 (Drug)
ATG-010 + Chemotherapeutics
perimental: ATG-010 + Chemotherapeutics ATG-010: Oral, 80 mg QW, Day 1/week of treatment cycles +Paclitaxel: 175 mg/m2, intravenous infusion >3 h, Day 1, Q3W; ATG-010: Oral, 80 mg QW, Day
1/week of treatment cycles +Carboplatin: AUC = 5, intravenous infusion >1 h, Day 1, Q3W or Cisplatin: 75 mg/m2, intravenous infusion >1h, Day 2, Q3W ; ATG-010: Oral, 80 mg QW, Day 1/week of treatment cycles +Doxorubicin hydrochloride liposome, 40 mg/ m2, Day 1; Q4W;
干预措施: ATG-010 (Drug)
结局指标
主要结局
Objective response rate(ORR)
时间窗: 26 months
Objective response rate(ORR)
次要结局
- Time to response(TTR)(26 months)
- Duration of Response(DOR)(26 months)
- Disease control rate(DCR)(26 months)
- Overall Survival(OS)(26 months)
- Progression-Free Survival(PFS)(26 months)
- The incidence,severity,and causality of AE,SAE(26 months)
- EORTC-QLQ-C30(26 months)
研究者
Qi Zhou
Academic leaders of Gynecologic Oncology Department
Chongqing University Cancer Hospital