A Phase II, Open-Label, Multicenter, Platform Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 176
- 试验地点
- 81
- 主要终点
- Confirmed Objective Response Rate (ORR)
研究概览
简要总结
This study will evaluate the efficacy and safety of multiple biomarker-selected treatments in patients with persistent or recurrent rare epithelial ovarian, fallopian tube, or primary peritoneal tumors. Enrollment will take place in two phases: a preliminary phase followed by a potential expansion phase.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Persistent or recurrent EOC that meets the following criteria: Histologically confirmed non-high-grade serous, non-high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, including but not limited to low-grade serous ovarian carcinoma, clear cell carcinoma, mucinous carcinoma, carcinosarcoma, undifferentiated carcinoma, seromucinous carcinoma, malignant Brenner tumors, Grades 1 or 2 endometrioid carcinoma, mesonephric-like adenocarcinoma and small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Disease that is not amenable to curative surgery
- •Measurable disease (at least one target lesion) according to RECIST v1.1
- •Previous treatment with one to four lines of therapy, at least one of which was platinum-based. Hormonal therapy does not count as a line of therapy.
- •Platinum-resistant disease, defined as disease progression during or within 6 months of last platinum therapy, with the following exception: Participants with primary platinum-refractory disease are excluded.
- •Submission of a representative tumor specimen that is suitable for next-generation sequencing (NGS) testing and estrogen receptor immunohistochemistry (ER IHC) to determine treatment arm assignment and for central pathology review.
- •Submission of the local pathology report and, if available, any associated stained slides that supported the local diagnosis of the histology (to be used for central pathology review)
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Adequate hematologic and end-organ function
- •For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs (if applicable)
- •In addition to the general inclusion criteria above, participants must meet all of the arm-specific inclusion criteria for the respective arm
排除标准
- •Pregnant or breastfeeding, or intending to become pregnant or breastfeed during the study
- •Primary platinum-refractory disease, defined as progression during or within 4 weeks after the last dose of the first-line platinum treatment
- •Histologic diagnosis of high-grade serous or high-grade endometrioid ovarian, fallopian tube, or primary peritoneal cancer
- •Current diagnosis of solely borderline epithelial ovarian tumor
- •Current diagnosis of non-epithelial ovarian tumors
- •Current diagnosis of synchronous primary endometrial cancer
- •Prior history of primary endometrial cancer, with the following exception: a prior diagnosis of primary endometrial cancer is permitted if it meets all of the following conditions: Stage IA, no lymphovascular invasion, International Federation of Gynecology and Obstetrics Grade 1 or 2, not a high-grade subtype.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Symptomatic, untreated, or actively progressing CNS metastases
- •Severe infection within 4 weeks prior to initiation of study treatment
- •Treatment with chemotherapy, radiotherapy, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, or investigational therapy within 28 days prior to initiation of study treatment
- •Treatment with hormonal therapy within 14 days prior to initiation of study treatment
- •In addition to the general exclusion criteria above, participants can not meet any of the arm-specific exclusion criteria for the respective arm
研究组 & 干预措施
Giredestrant + Abemaciclib (ER+ tumors)
Participants in the Giredestrant + Abemaciclib arm will receive treatment until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Abemaciclib (Drug)
Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors)
Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Letrozole (Drug)
Inavolisib + Giredestrant (ER+ and PIK3CA-altered tumors)
Participants in the Inavolisib + Giredestrant arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Giredestrant (Drug)
Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors)
Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Luteinizing Hormone-Releasing Hormone (LHRH) Agonists (Drug)
Ipatasertib + Paclitaxel (PIK3CA/AKT1/PTEN-altered tumors)
Participants in the Ipatasertib + Paclitaxel arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Ipatasertib (Drug)
Ipatasertib + Paclitaxel (PIK3CA/AKT1/PTEN-altered tumors)
Participants in the Ipatasertib + Paclitaxel arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Paclitaxel (Drug)
Cobimetinib (BRAF/NRAS/KRAS/NF1-altered tumors)
Participants in the Cobimetinib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Cobimetinib (Drug)
Trastuzumab Emtansine (ERBB2-amplified/mutant tumors)
Participants in the Trastuzumab Emtansine arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Trastuzumab Emtansine (Drug)
Atezolizumab + Bevacizumab (Non-matched)
Participants in the Atezolizumab + Bevacizumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
干预措施: Atezolizumab (Drug)
Inavolisib + Palbociclib (PIK3CA-altered tumors)
Participants in the Inavolisib + Palbociclib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Palbociclib (Drug)
Inavolisib + Giredestrant (ER+ and PIK3CA-altered tumors)
Participants in the Inavolisib + Giredestrant arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Inavolisib (Drug)
Inavolisib + Olaparib (Non-matched)
Participants in the Inavolisib + Olaparib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Inavolisib (Drug)
Inavolisib + Bevacizumab (PIK3CA-altered tumors)
Participants in the Inavolisib + Bevacizumab arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Bevacizumab (Drug)
Inavolisib + Bevacizumab (PIK3CA-altered tumors)
Participants in the Inavolisib + Bevacizumab arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Inavolisib (Drug)
Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched)
Participants in the Atezolizumab + Bevacizumab + Cyclophosphamide arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
干预措施: Cyclophosphamide (Drug)
Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched)
Participants in the Atezolizumab + Bevacizumab + Cyclophosphamide arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
干预措施: Atezolizumab (Drug)
Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched)
Participants in the Atezolizumab + Bevacizumab + Cyclophosphamide arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
干预措施: Bevacizumab (Drug)
Giredestrant + Abemaciclib (ER+ tumors)
Participants in the Giredestrant + Abemaciclib arm will receive treatment until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Luteinizing Hormone-Releasing Hormone (LHRH) Agonists (Drug)
Giredestrant + Abemaciclib (ER+ tumors)
Participants in the Giredestrant + Abemaciclib arm will receive treatment until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Giredestrant (Drug)
Atezolizumab + Bevacizumab (Non-matched)
Participants in the Atezolizumab + Bevacizumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
干预措施: Bevacizumab (Drug)
Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors)
Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Inavolisib (Drug)
Inavolisib + Palbociclib (PIK3CA-altered tumors)
Participants in the Inavolisib + Palbociclib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Inavolisib (Drug)
Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors)
Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Palbociclib (Drug)
Inavolisib + Olaparib (Non-matched)
Participants in the Inavolisib + Olaparib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
干预措施: Olaparib (Drug)
结局指标
主要结局
Confirmed Objective Response Rate (ORR)
时间窗: Up to approximately 5 years
Confirmed ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) (demonstrated on two consecutive occasions \>=4 weeks apart), as determined by the investigator according to RECIST v1.1.
次要结局
- Duration of Response (DOR)(Up to approximately 5 years)
- Disease Contral Rate (DCR)(Up to approximately 5 years)
- DCR as Determined by IRC(Up to approximately 5 years)
- 6-Month PFS Rate(Up to 6 month)
- DOR as Determined by IRC(Up to approximately 5 years)
- Overall Survival (OS)(Up to approximately 5 years)
- Progression Free Survival (PFS)(Up to approximately 5 years)
- Confirmed ORR as Determined by IRC (Independent Review Committee)(Up to approximately 5 years)
- PFS as Determined by IRC(Up to approximately 5 years)
- Percentage of Participants With Adverse Events(Up to approximately 5 years)