Personalized Timing of Interval Debulking Surgery Based on KELIM After Neoadjuvant Chemotherapy in Advanced Ovarian Cancer - a Multicenter Randomized Phase II Non-inferiority Trial (PRESELECT-I Trial)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 126
- 试验地点
- 6
- 主要终点
- 12-month progression-free survival (PFS) rate by RECIST criteria
研究概览
简要总结
About 70% of epithelial ovarian cancer patients are diagnosed at advanced stage. When primary optimal surgery is not possible, neoadjuvant chemotherapy will followed by interval debulking surgery is one treatment option. However, there is no consensus on the optimal timing of the surgery. CA125 is a well-known tumor marker in ovarian cancer. Its kinetic change has been proven to correlate with the patients' response to chemotherapy and chance of optimal resection. This study aims to utilize the kinetic change of CA125 to customize the timing of surgery for individual patients and compare this with the standard clinical practice.
详细描述
Recruited patients will be randomised into two groups. The control group will receive treatment according to the standard clinical practice. The investigation group will have an additional CA125 at the 5th week after the first cycle of chemotherapy. CA-125 ELIMination Rate Constant K (KELIM) will be determined using online tool. Patients with KELIM =>1 will receive radiological assessment and undergo internal debulking surgery if the disease is operable. Patients with KELIM <1 will have alternative management, such as addition of bevacizumab or changing to dose-dense chemotherapy, and defer the interval debulking surgery.
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
- Single (Outcomes Assessor)
盲法说明
Completeness of resection is assessed by independent surgeon
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
- •Patients aged 18 years old or older
- •Patients with Eastern Cooperative Oncology Group score 0-1 within 28 days prior to recruitment
- •Patients who can sign the informed consent
- •Patients with stage III-IV histologically or cytologically confirmed epithelial ovarian cancer (EOC), fallopian tube or primary peritoneal cancer not amenable for PDS
- •Patients who have baseline computed tomography (CT) of thorax, abdomen and pelvis.
- •Patients who are planned for neoadjuvant chemotherapy (NACT) using 3-weekly carboplatin and paclitaxel. Those who have received one cycle of NACT may be eligible if the CA125 schedule of the study group can be matched.
- •Patients who have an evaluable CA125 level at baseline (i.e., baseline level is at least 2x upper limit of normal)
- •Patients who agree for chemotherapy and interval debulking surgery (IDS) if the disease becomes operable after NACT
- •Patients with adequate hematologic, liver and renal functions for chemotherapy
- •Patients who agree to receive adjuvant chemotherapy after IDS. The total number of NACT and adjuvant chemotherapy should be four or above, up to maximum of 9 cycles.
- •Patients who have childbearing potential should practice highly effective contraception throughout the study until at least 30 days after completion of the treatment.
- •Patients must have either germline and / or somatic BRCA test, or homologous recombination deficiency (HRD) test.
排除标准
- •Patients who have borderline malignancy, or non-EOC like germ cell or sex cord tumor, or metastatic diseases from other origins
- •Patients with mucinous and neuroendocrine histology
- •Patients with history of other malignancies within five years
- •Patients who are eligible for primary debulking surgery (PDS)
- •Patients who cannot undergo PDS because of parametrial and/or vaginal involvement alone
- •Patients who are not fit for PDS because of medical morbidities or refusal of operation
- •Patients who have already started NACT outside the study centers, except those who have received only one cycle within 7 days and the baseline CA125 value within 3 days of NACT (normal cut-off 35 U/ml) is available
- •Patients who participate in other interventional studies
- •Patients who are pregnant or breastfeeding
- •Patients who have contraindications to platinum-based chemotherapy
- •Patents with active tuberculosis, history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded.
研究组 & 干预措施
Standard clinical practice
Participants will follow the standard practice and receive 3-6 cycles of neoadjuvant chemotherapy, followed by radiological assessment and interval debulking surgery.
干预措施: Carboplatin plus Paclitaxel (Drug)
Standard clinical practice
Participants will follow the standard practice and receive 3-6 cycles of neoadjuvant chemotherapy, followed by radiological assessment and interval debulking surgery.
干预措施: Interval debulking surgery (Procedure)
Personalised management
Patients will be managed based on CA-125 ELIMination Rate Constant K (KELIM) at the neoadjuvant setting.
干预措施: KELIM (Diagnostic Test)
Personalised management
Patients will be managed based on CA-125 ELIMination Rate Constant K (KELIM) at the neoadjuvant setting.
干预措施: Carboplatin plus Paclitaxel (Drug)
Personalised management
Patients will be managed based on CA-125 ELIMination Rate Constant K (KELIM) at the neoadjuvant setting.
干预措施: Interval debulking surgery (Procedure)
结局指标
主要结局
12-month progression-free survival (PFS) rate by RECIST criteria
时间窗: up to 24 months from randomisation
PFS is defined as the time from the date of randomization until the date of progressive disease or death (whichever comes first).
Complete resection (CC0) rate
时间窗: up to 24 weeks from randomisation
The likelihood of CC0 in patients who undergo IDS when KELIM reaches \>=1
次要结局
- Overall survival (OS)(Up to 5 years from randomisation)
- Incidence of adverse events(up to 1 year from randomisation)
- Progression-free survival (PFS) by RECIST criteria(up to 5 years from randomisation)
- Quality-of-life scale(up to 1 year from randomisation)
- Chemotherapy response score (CRS)(up to 24 weeks from randomisation)
研究者
Dr. Ka-Yu Tse
Prof.
The University of Hong Kong